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Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: a systematic review and meta-analysis.

Background: Bipolar disorder affects up to one in 25 individuals and identification of early risk indicators of negative outcomes could facilitate early detection of patients with greatest clinical needs and risk. We aimed to investigate the association between childhood maltreatment and key negative outcomes in patients with bipolar disorder. Methods: For this systematic review and meta-analysis we searched MEDLINE, PsycINFO, and Embase to identify articles published before Jan 1, 2015, examining the association of maltreatment (physical, sexual, or emotional abuse, neglect, or family conflict) before age 18 years with clinical features and course of illness in bipolar disorder. Data were extracted from published reports and any missing information was requested from investigators. We did 12 independent random-effects meta-analyses to quantify the associations between childhood maltreatment and course of illness or clinical features. Findings: We initially identified 527 records and after unsuitable studies were removed, our search yielded 148 publications of which 30 were used in the meta-analysis. Patients with bipolar disorder and history of childhood maltreatment had greater mania severity (six studies, 780 participants; odds ratio [OR] 2·02, 95% CI 1·21-3·39, p=0·008), greater depression severity (eight studies, 1007 participants; 1·57, 1·25-1·99, p=0·0001), greater psychosis severity (seven studies, 1494 participants; 1·49, 1·10-2·04, p=0·011), higher risk of comorbidity with post-traumatic stress disorder (eight studies, 2494 participants; 3·60, 2·45-5·30, p<0·0001), anxiety disorders (seven studies, 5091 participants; 1·90, 1·39-2·61, p<0·0001), substance misuse disorders (11 studies, 5469 participants; 1·84, 1·41-2·39, p<0·0001), alcohol misuse disorder (eight studies, 5040 participants; 1·44, 1·13-1·83, p=0·003), earlier age of bipolar disorder onset (14 studies, 5733 participants; 1·85, 1·43-2·40, p<0·0001), higher risk of rapid cycling (eight studies, 3010 participants; 1·89, 1·45-2·48, p<0·0001), greater number of manic episodes (seven studies, 3909 participants; 1·26, 1·09-1·47, p=0·003), greater number of depressive episodes (eight studies, 4025 participants; 1·38, 1·07-1·79, p=0·013), and higher risk of suicide attempt (13 studies, 3422 participants; 2·25, 1·88-2·70, p<0·0001) compared with those with bipolar disorder without childhood maltreatment. Overall, these associations were not explained by publication bias, undue effects of individual studies, or variation in study quality. Interpretation: Childhood maltreatment predicts unfavourable clinical features and course of illness in patients with bipolar disorder. Funding: None.

The lancet. Psychiatry · meta-analysis · 278 citationsread the source →

Diagnosis and Management of Infertility: A Review.

Importance: In the US, approximately 12.7% of reproductive age women seek treatment for infertility each year. This review summarizes current evidence regarding diagnosis and treatment of infertility. Observations: Infertility is defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse. Approximately 85% of infertile couples have an identifiable cause. The most common causes of infertility are ovulatory dysfunction, male factor infertility, and tubal disease. The remaining 15% of infertile couples have "unexplained infertility." Lifestyle and environmental factors, such as smoking and obesity, can adversely affect fertility. Ovulatory disorders account for approximately 25% of infertility diagnoses; 70% of women with anovulation have polycystic ovary syndrome. Infertility can also be a marker of an underlying chronic disease associated with infertility. Clomiphene citrate, aromatase inhibitors such as letrozole, and gonadotropins are used to induce ovulation or for ovarian stimulation during in vitro fertilization (IVF) cycles. Adverse effects of gonadotropins include multiple pregnancy (up to 36% of cycles, depending on specific therapy) and ovarian hyperstimulation syndrome (1%-5% of cycles), consisting of ascites, electrolyte imbalance, and hypercoagulability. For individuals presenting with anovulation, ovulation induction with timed intercourse is often the appropriate initial treatment choice. For couples with unexplained infertility, endometriosis, or mild male factor infertility, an initial 3 to 4 cycles of ovarian stimulation may be pursued; IVF should be considered if these approaches do not result in pregnancy. Because female fecundity declines with age, this factor should guide decision-making. Immediate IVF may be considered as a first-line treatment strategy in women older than 38 to 40 years. IVF is also indicated in cases of severe male factor infertility or untreated bilateral tubal factor. Conclusions and relevance: Approximately 1 in 8 women aged 15 to 49 years receive infertility services. Although success rates vary by age and diagnosis, accurate diagnosis and effective therapy along with shared decision-making can facilitate achievement of fertility goals in many couples treated for infertility.

JAMA · review · 849 citationsread the source →

Relationship between 25-hydroxyvitamin D and cognitive function in older adults: the Health, Aging and Body Composition Study.

Objectives: To examine the relationship between 25-hydroxyvitamin D (25(OH)D) levels and cognitive performance over time in older adults in the Health, Aging and Body Composition (Health ABC) Study. Design: Prospective cohort study. Setting: Community-dwelling participants in Pittsburgh, Pennsylvania, and Memphis, Tennessee. Participants: Well-functioning adults aged 70 to 79 at baseline with serum 25(OH)D measured at the 12-month follow-up visit and cognitive function measured at baseline and 4-year follow-up visit (N = 2,777). Measurements: Vitamin D status was categorized as 25(OH)D levels of less than 20.0 ng/mL, 20.0 to 29.9 ng/mL, or 30.0 ng/mL or greater. Cognition was measured using the modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST). Linear regression models adjusting for multiple covariates, including age, education, sex, race, site, season, physical activity, and comorbidities, were used in the analysis. Results: Sixty-eight percent of participants had 25(OH)D levels of less than 30.0 ng/mL. Lower 25(OH)D levels were associated with lower baseline cognitive scores on the 3MS (adjusted mean 89.9, 95% confidence interval (CI) = 89.4-90.4 for <20.0 ng/mL; adjusted mean 90.8, 95% CI = 90.4-91.3 for 20.0-29.9 ng/mL; adjusted mean 90.6, 95% CI = 90.2-91.1 for ≥ 30.0 ng/mL; P trend = .02) and the DSST (adjusted mean 35.2, 95% CI = 34.5-36.0 for <20.0 ng/mL; adjusted mean 35.9, 95% CI = 35.2-36.6 for 20.0-29.9 ng/mL; adjusted mean 37.0, 95% CI = 36.3-37.8 for ≥ 30.0 ng/mL; P trend = .01). Participants with low 25(OH)D levels had greater declines in 3MS scores over 4 years than those with higher levels (least square mean change -1.0, 95% CI = -1.5 to -0.6 for <20.0 ng/mL; least square mean change -0.8, 95% CI = -1.2 to -0.3 for 20.0-29.9 ng/mL; least square mean change -0.2, 95% CI = -0.7 to 0.2 for ≥30.0 ng/mL; P = .05). There was no significant difference in DSST decline according to 25(OH)D level. Conclusion: Low 25(OH)D levels were associated with worse global cognitive function and greater decline over time according to the 3MS. Intervention trials are needed to determine whether vitamin D supplementation can reduce cognitive decline.

Journal of the American Geriatrics Society · cohort or longitudinal · 49 citationsread the source →

Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2014. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system that provides estimates of the prevalence of autism spectrum disorder (ASD) among children aged 8 years whose parents or guardians reside within 11 ADDM sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). ADDM surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by professional service providers in the community. Staff completing record review and abstraction receive extensive training and supervision and are evaluated according to strict reliability standards to certify effective initial training, identify ongoing training needs, and ensure adherence to the prescribed methodology. Record review and abstraction occurs in a variety of data sources ranging from general pediatric health clinics to specialized programs serving children with developmental disabilities. In addition, most of the ADDM sites also review records for children who have received special education services in public schools. In the second phase of the study, all abstracted information is reviewed systematically by experienced clinicians to determine ASD case status. A child is considered to meet the surveillance case definition for ASD if he or she displays behaviors, as described on one or more comprehensive evaluations completed by community-based professional providers, consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for autistic disorder; pervasive developmental disorder-not otherwise specified (PDD-NOS, including atypical autism); or Asperger disorder. This report provides updated ASD prevalence estimates for children aged 8 years during the 2014 surveillance year, on the basis of DSM-IV-TR criteria, and describes characteristics of the population of children with ASD. In 2013, the American Psychiatric Association published the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which made considerable changes to ASD diagnostic criteria. The change in ASD diagnostic criteria might influence ADDM ASD prevalence estimates; therefore, most (85%) of the records used to determine prevalence estimates based on DSM-IV-TR criteria underwent additional review under a newly operationalized surveillance case definition for ASD consistent with the DSM-5 diagnostic criteria. Children meeting this new surveillance case definition could qualify on the basis of one or both of the following criteria, as documented in abstracted comprehensive evaluations: 1) behaviors consistent with the DSM-5 diagnostic features; and/or 2) an ASD diagnosis, whether based on DSM-IV-TR or DSM-5 diagnostic criteria. Stratified comparisons of the number of children meeting either of these two case definitions also are reported. RESULTS: For 2014, the overall prevalence of ASD among the 11 ADDM sites was 16.8 per 1,000 (one in 59) children aged 8 years. Overall ASD prevalence estimates varied among sites, from 13.1-29.3 per 1,000 children aged 8 years. ASD prevalence estimates also varied by sex and race/ethnicity. Males were four times more likely than females to be identified with ASD. Prevalence estimates were higher for non-Hispanic white (henceforth, white) children compared with non-Hispanic black (henceforth, black) children, and both groups were more likely to be identified with ASD compared with Hispanic children. Among the nine sites with sufficient data on intellectual ability, 31% of children with ASD were classified in the range of intellectual disability (intelligence quotient [IQ] <70), 25% were in the borderline range (IQ 71-85), and 44% had IQ scores in the average to above average range (i.e., IQ >85). The distribution of intellectual ability varied by sex and race/ethnicity. Although mention of developmental concerns by age 36 months was documented for 85% of children with ASD, only 42% had a comprehensive evaluation on record by age 36 months. The median age of earliest known ASD diagnosis was 52 months and did not differ significantly by sex or race/ethnicity. For the targeted comparison of DSM-IV-TR and DSM-5 results, the number and characteristics of children meeting the newly operationalized DSM-5 case definition for ASD were similar to those meeting the DSM-IV-TR case definition, with DSM-IV-TR case counts exceeding DSM-5 counts by less than 5% and approximately 86% overlap between the two case definitions (kappa = 0.85). INTERPRETATION: Findings from the ADDM Network, on the basis of 2014 data reported from 11 sites, provide updated population-based estimates of the prevalence of ASD among children aged 8 years in multiple communities in the United States. The overall ASD prevalence estimate of 16.8 per 1,000 children aged 8 years in 2014 is higher than previously reported estimates from the ADDM Network. Because the ADDM sites do not provide a representative sample of the entire United States, the combined prevalence estimates presented in this report cannot be generalized to all children aged 8 years in the United States. Consistent with reports from previous ADDM surveillance years, findings from 2014 were marked by variation in ASD prevalence when stratified by geographic area, sex, and level of intellectual ability. Differences in prevalence estimates between black and white children have diminished in most sites, but remained notable for Hispanic children. For 2014, results from application of the DSM-IV-TR and DSM-5 case definitions were similar, overall and when stratified by sex, race/ethnicity, DSM-IV-TR diagnostic subtype, or level of intellectual ability. PUBLIC HEALTH ACTION: Beginning with surveillance year 2016, the DSM-5 case definition will serve as the basis for ADDM estimates of ASD prevalence in future surveillance reports. Although the DSM-IV-TR case definition will eventually be phased out, it will be applied in a limited geographic area to offer additional data for comparison. Future analyses will examine trends in the continued use of DSM-IV-TR diagnoses, such as autistic disorder, PDD-NOS, and Asperger disorder in health and education records, documentation of symptoms consistent with DSM-5 terminology, and how these trends might influence estimates of ASD prevalence over time. The latest findings from the ADDM Network provide evidence that the prevalence of ASD is higher than previously reported estimates and continues to vary among certain racial/ethnic groups and communities. With prevalence of ASD ranging from 13.1 to 29.3 per 1,000 children aged 8 years in different communities throughout the United States, the need for behavioral, educational, residential, and occupational services remains high, as does the need for increased research on both genetic and nongenetic risk factors for ASD.

MMWR Surveillance Summaries · 5532 citationsread the source →

Association between maternal age at childbirth and child and adult outcomes in the offspring: a prospective study in five low-income and middle-income countries (COHORTS collaboration).

Background: Both young and advanced maternal age is associated with adverse birth and child outcomes. Few studies have examined these associations in low-income and middle-income countries (LMICs) and none have studied adult outcomes in the offspring. We aimed to examine both child and adult outcomes in five LMICs. Methods: In this prospective study, we pooled data from COHORTS (Consortium for Health Orientated Research in Transitioning Societies)-a collaboration of five birth cohorts from LMICs (Brazil, Guatemala, India, the Philippines, and South Africa), in which mothers were recruited before or during pregnancy, and the children followed up to adulthood. We examined associations between maternal age and offspring birthweight, gestational age at birth, height-for-age and weight-for-height Z scores in childhood, attained schooling, and adult height, body composition (body-mass index, waist circumference, fat, and lean mass), and cardiometabolic risk factors (blood pressure and fasting plasma glucose concentration), along with binary variables derived from these. Analyses were unadjusted and adjusted for maternal socioeconomic status, height and parity, and breastfeeding duration. Findings: We obtained data for 22 188 mothers from the five cohorts, enrolment into which took place at various times between 1969 and 1989. Data for maternal age and at least one outcome were available for 19 403 offspring (87%). In unadjusted analyses, younger (≤19 years) and older (≥35 years) maternal age were associated with lower birthweight, gestational age, child nutritional status, and schooling. After adjustment, associations with younger maternal age remained for low birthweight (odds ratio [OR] 1·18 (95% CI 1·02-1·36)], preterm birth (1·26 [1·03-1·53]), 2-year stunting (1·46 [1·25-1·70]), and failure to complete secondary schooling (1·38 [1·18-1·62]) compared with mothers aged 20-24 years. After adjustment, older maternal age remained associated with increased risk of preterm birth (OR 1·33 [95% CI 1·05-1·67]), but children of older mothers had less 2-year stunting (0·64 [0·54-0·77]) and failure to complete secondary schooling (0·59 [0·48-0·71]) than did those with mothers aged 20-24 years. Offspring of both younger and older mothers had higher adult fasting glucose concentrations (roughly 0·05 mmol/L). Interpretation: Children of young mothers in LMICs are disadvantaged at birth and in childhood nutrition and schooling. Efforts to prevent early childbearing should be strengthened. After adjustment for confounders, children of older mothers have advantages in nutritional status and schooling. Extremes of maternal age could be associated with disturbed offspring glucose metabolism. Funding: Wellcome Trust and the Bill & Melinda Gates Foundation.

The Lancet. Global health · 316 citationsread the source →

Impact of Intermittent Fasting Combined With High-Intensity Interval Training on Body Composition, Metabolic Biomarkers, and Physical Fitness in Women With Obesity.

Background: Intermittent fasting (IF) is a dietary approach that is widely popular due to its effects on weight and body fat loss, but it does not appear to ensure muscle mass preservation. Incorporating high-intensity interval training (HIIT) into an individual's routine could be an attractive and viable therapeutic option for improving body composition, lifestyle and health promotion. Problematizing the emerging situation of fighting obesity, led us to clarify gaps about IF and hypothesize that IF and HIIT in conjunction may protect against muscle mass decline without impairing nitrogen balance (NB), in addition to improving the physical fitness of women with obesity. Objectives: To evaluate the effects of IF alone and combined with HIIT on body composition, NB and strength and physical fitness in women with obesity. Methods: Thirty-six women (BMI 34.0 ± 3.2; 32.2 ± 4.4 years) participated and were randomly distributed into three groups: (1) Intermittent fasting combined with exercise group (IF + EX); (2) Exercise group (EX); and (3) Intermittent fasting group (IF). The interventions took place over 8 weeks and all evaluations were performed pre and post-intervention. The HIIT circuit was performed 3x/week, for 25 mins/session, at 70-85% of the maximum heart rate. The intermittent fasting protocol was a 5:2 diet with two meals within 6 h on fasting days, being 25% of total energy intake, plus 18 h of complete fasting. The protocol was performed 2x/week and 5 days of ad libitum ingestion. Resting metabolic rate (RMR) was measured by indirect calorimetry, body composition by BodPod®, NB from urinary nitrogen, food consumption by food records and physical and strength performance were measured by physical tests. ANOVA two-way repeated measures mixed model was performed followed by Sidak post hoc (p < 0.05). This project was registered in ClinicalTrials.gov, NCT05237154. Results: There were a reduction in body weight (P = 0.012) and BMI (P = 0.031) only in the IF + EX group. There was body fat loss in the IF + EX group (-4%, P < 0.001) and in the EX group (-2.3%, P = 0.043), an increase in fat-free mass in the IF + EX group (+3.3%, P < 0.001) and also in the EX group (+2%, P = 0.043), without differences between groups and the IF group showed no changes. The NB was equilibrium in all groups. All parameters of aerobic capacity and strength improved. Conclusion: Combining IF with HIIT can promote increments in fat-free mass, NB equilibrium and improve physical fitness and strength.

Frontiers in nutrition · 23 citationsread the source →

Maximizing clinical research participation in vulnerable older persons: identification of barriers and motivators.

Objectives: To identify barriers and motivators to participation in long-term clinical research by high-risk elderly people and to develop procedures to maximize recruitment and retention. Design: Quantitative and qualitative survey. Setting: Academic primary care medicine and pre-anesthesia testing clinics. Participants: Fifty patients aged 70 and older, including 25 medical patients at high risk of hospitalization and 25 patients with planned major surgery. Measurements: Fifteen- to 20-minute interviews involved open- and closed-ended questions guided by an in-depth script. Two planned study protocols were presented to each participant. Both involved serial neuropsychological assessments, blood testing, and magnetic resonance brain imaging (MRI); one added lumbar puncture (LP). Participants were asked whether they would be willing to participate in these protocols, rated barriers and incentives to participation, and were probed with open-ended questions. Results: Of 50 participants (average age 78, 44% male, 40% nonwhite), 32 (64%) expressed willingness to participate in the LP-containing protocol, with LP cited as the strongest disincentive. Thirty-eight (76%) expressed willingness to participate in the protocol without LP, with phlebotomy and long interviews cited as the strongest disincentives. Altruism was a strong motivator for participation, whereas transportation was a major barrier. Study visits at home, flexible appointment times, assessments shorter than 75 minutes, and providing transportation and free parking were strategies developed to maximize study participation. Conclusion: Vulnerable elderly people expressed a high rate of willingness to participate in an 18-month prospective study. Participants identified incentives and barriers that enabled investigators to develop procedures to maximize recruitment and retention.

Journal of the American Geriatrics Society · 56 citationsread the source →

Populations and Interventions for Palliative and End-of-Life Care: A Systematic Review.

Importance: Evidence supports palliative care effectiveness. Given workforce constraints and the costs of new services, payers and providers need help to prioritize their investments. They need to know which patients to target, which personnel to hire, and which services best improve outcomes. Objective: To inform how payers and providers should identify patients with "advanced illness" and the specific interventions they should implement, we reviewed the evidence to identify (1) individuals appropriate for palliative care and (2) elements of health service interventions (personnel involved, use of multidisciplinary teams, and settings of care) effective in achieving better outcomes for patients, caregivers, and the healthcare system. Evidence review: Systematic searches of MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Database of Systematic Reviews databases (1/1/2001-1/8/2015). Results: Randomized controlled trials (124) met inclusion criteria. The majority of studies in cancer (49%, 38 of 77 studies) demonstrated statistically significant patient or caregiver outcomes (e.g., p < 0.05), as did those in congestive heart failure (CHF) (62%, 13 of 21), chronic obstructive pulmonary disease (COPD; 58%, 11 of 19), and dementia (60%, 15 of 25). Most prognostic criteria used clinicians' judgment (73%, 22 of 30). Most interventions included a nurse (70%, 69 of 98), and many were nurse-only (39%, 27 of 69). Social workers were well represented, and home-based approaches were common (56%, 70 of 124). Home interventions with visits were more effective than those without (64%, 28 of 44; vs. 46%, 12 of 26). Interventions improved communication and care planning (70%, 12 of 18), psychosocial health (36%, 12 of 33, for depressive symptoms; 41%, 9 of 22, for anxiety), and patient (40%, 8 of 20) and caregiver experiences (63%, 5 of 8). Many interventions reduced hospital use (65%, 11 of 17), but most other economic outcomes, including costs, were poorly characterized. Palliative care teams did not reliably lower healthcare costs (20%, 2 of 10). Conclusions: Palliative care improves cancer, CHF, COPD, and dementia outcomes. Effective models include nurses, social workers, and home-based components, and a focus on communication, psychosocial support, and the patient or caregiver experience. High-quality research on intervention costs and cost outcomes in palliative care is limited.

Journal of palliative medicine · systematic review · 135 citationsread the source →

Cognitive behavioural therapy for tinnitus.

Background: Tinnitus affects up to 21% of the adult population with an estimated 1% to 3% experiencing severe problems. Cognitive behavioural therapy (CBT) is a collection of psychological treatments based on the cognitive and behavioural traditions in psychology and often used to treat people suffering from tinnitus. Objectives: To assess the effects and safety of CBT for tinnitus in adults. Search methods: The Cochrane ENT Information Specialist searched the ENT Trials Register; CENTRAL (2019, Issue 11); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 November 2019. Selection criteria: Randomised controlled trials (RCTs) of CBT versus no intervention, audiological care, tinnitus retraining therapy or any other active treatment in adult participants with tinnitus. Data collection and analysis: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were the impact of tinnitus on disease-specific quality of life and serious adverse effects. Our secondary outcomes were: depression, anxiety, general health-related quality of life, negatively biased interpretations of tinnitus and other adverse effects. We used GRADE to assess the certainty of evidence for each outcome. Main results: We included 28 studies (mostly from Europe) with a total of 2733 participants. All participants had had tinnitus for at least three months and their average age ranged from 43 to 70 years. The duration of the CBT ranged from 3 to 22 weeks and it was mostly conducted in hospitals or online. There were four comparisons and we were interested in outcomes at end of treatment, and 6 and 12 months follow-up. The results below only refer to outcomes at end of treatment due to an absence of evidence at the other follow-up time points. CBT versus no intervention/wait list control Fourteen studies compared CBT with no intervention/wait list control. For the primary outcome, CBT may reduce the impact of tinnitus on quality of life at treatment end (standardised mean difference (SMD) -0.56, 95% confidence interval (CI) -0.83 to -0.30; 10 studies; 537 participants; low certainty). Re-expressed as a score on the Tinnitus Handicap Inventory (THI; range 0 to 100) this is equivalent to a score 10.91 points lower in the CBT group, with an estimated minimal clinically important difference (MCID) for this scale being 7 points. Seven studies, rated as moderate certainty, either reported or informed us via personal communication about serious adverse effects. CBT probably results in little or no difference in adverse effects: six studies reported none and in one study one participant in the CBT condition worsened (risk ratio (RR) 3.00, 95% CI 0.13 to 69.87). For the secondary outcomes, CBT may result in a slight reduction in depression (SMD -0.34, 95% CI-0.60 to -0.08; 8 studies; 502 participants; low certainty). However, we are uncertain whether CBT reduces anxiety, improves health-related quality of life or reduces negatively biased interpretations of tinnitus (all very low certainty). From seven studies, no other adverse effects were reported (moderate certainty). CBT versus audiological care Three studies compared CBT with audiological care. CBT probably reduces the impact of tinnitus on quality of life when compared with audiological care as measured by the THI (range 0 to 100; mean difference (MD) -5.65, 95% CI -9.79 to -1.50; 3 studies; 444 participants) (moderate certainty; MCID = 7 points). No serious adverse effects occurred in the two included studies reporting these, thus risk ratios were not calculated (moderate certainty). The evidence suggests that CBT may slightly reduce depression but may result in little or no difference in anxiety or health-related quality of life (all low certainty) when compared with audiological care. CBT may reduce negatively biased interpretations of tinnitus when compared with audiological care (low certainty). No other adverse effects were reported for either group (moderate certainty). CBT versus tinnitus retraining therapy (TRT) One study compared CBT with TRT (including bilateral sound generators as per TRT protocol). CBT may reduce the impact of tinnitus on quality of life as measured by the THI when compared with TRT (range 0 to 100) (MD -15.79, 95% CI -27.91 to -3.67; 1 study; 42 participants; low certainty). For serious adverse effects three participants deteriorated during the study: one in the CBT (n = 22) and two in the TRT group (n = 20) (RR 0.45, 95% CI 0.04 to 4.64; low certainty). We are uncertain whether CBT reduces depression and anxiety or improves health-related quality of life (low certainty). CBT may reduce negatively biased interpretations of tinnitus. No data were available for other adverse effects. CBT versus other active control Sixteen studies compared CBT with another active control (e.g. relaxation, information, Internet-based discussion forums). CBT may reduce the impact of tinnitus on quality of life when compared with other active treatments (SMD -0.30, 95% CI -0.55 to -0.05; 12 studies; 966 participants; low certainty). Re-expressed as a THI score this is equivalent to 5.84 points lower in the CBT group than the other active control group (MCID = 7 points). One study reported that three participants deteriorated: one in the CBT and two in the information only group (RR 1.70, 95% CI 0.16 to 18.36; low certainty). CBT may reduce depression and anxiety (both low certainty). We are uncertain whether CBT improves health-related quality of life compared with other control. CBT probably reduces negatively biased interpretations of tinnitus compared with other treatments. No data were available for other adverse effects. Authors' conclusions: CBT may be effective in reducing the negative impact that tinnitus can have on quality of life. There is, however, an absence of evidence at 6 or 12 months follow-up. There is also some evidence that adverse effects may be rare in adults with tinnitus receiving CBT, but this could be further investigated. CBT for tinnitus may have small additional benefit in reducing symptoms of depression although uncertainty remains due to concerns about the quality of the evidence. Overall, there is limited evidence for CBT for tinnitus improving anxiety, health-related quality of life or negatively biased interpretations of tinnitus.

The Cochrane database of systematic reviews · meta-analysis · 131 citationsread the source →

Mental health of migrants with pre-migration exposure to armed conflict: a systematic review and meta-analysis.

Background: Exposure to armed conflict has been associated with negative mental health consequences. We aimed to estimate the prevalence of generalised anxiety disorder, major depressive disorder, and post-traumatic stress disorder among migrants exposed to armed conflict. Methods: In this systematic review and meta-analysis, we searched online databases (Cochrane Library, Embase, LILACS, PsycInfo [via Ovid], PubMed, and Web of Science Core Collection) for relevant observational studies published between Jan 1, 1994, and June 28, 2021. We included studies that used standardised psychiatric interviews to assess generalised anxiety disorder, major depressive disorder, or post-traumatic stress disorder among migrants (refugees or internally displaced persons; aged ≥18 years) with pre-migration exposure to armed conflict. We excluded studies in which exposure to armed conflict could not be ascertained, studies that included a clinical population or people with chronic diseases that can trigger the onset of mental disease, and studies published before 1994. We used a random effects model to estimate each mental health disorder's pooled prevalence and random effects meta-regression to assess sources of heterogeneity. Two independent reviewers assessed the risk of bias for each study using the Joanna Briggs Institute Checklist for Prevalence Studies. The protocol was registered with PROSPERO, CRD42020209251. Findings: Of the 13 935 studies identified, 34 met our inclusion criteria; these studies accounted for 15 549 migrants. We estimated a prevalence of current post-traumatic stress disorder of 31% (95% CI 23-40); prevalence of current major depressive disorder of 25% (17-34); and prevalence of generalised anxiety disorder of 14% (5-35). Younger age was associated with a higher prevalence of current post-traumatic stress disorder (odds ratio 0·95 [95% CI 0·90-0·99]), lifetime post-traumatic stress disorder (0·88 [0·83-0·92]), and current generalised anxiety disorder (0·87 [0·78-0·97]). A longer time since displacement was associated with a lower lifetime prevalence of post-traumatic stress disorder (0·88 [0·81-0·95]) and major depressive disorder (0·81 [0·77-0·86]). Migrating to a middle-income (8·09 [3·06-21·40]) or low-income (39·29 [11·96-129·70]) country was associated with increased prevalence of generalised anxiety disorder. Interpretation: Migrants who are exposed to armed conflict are at high risk of mental health disorders. The mental health-care needs of migrants should be assessed soon after resettlement, and adequate care should be provided, with particular attention paid to young adults. Funding: Marie Skłodowska-Curie Actions (Horizon 2020-COFUND), MinCiencias (Colombia), and Swiss National Science Foundation.

The Lancet. Public health · meta-analysis · 111 citationsread the source →

Interventions for the treatment of metastatic extradural spinal cord compression in adults.

Background: Metastatic extradural spinal cord compression (MESCC) is treated with radiotherapy, corticosteroids, and surgery, but there is uncertainty regarding their comparative effects. This is an updated version of the original Cochrane review published in theCochrane Database of Systematic Reviews (Issue 4, 2008). Objectives: To determine the efficacy and safety of radiotherapy, surgery and corticosteroids in MESCC. Search methods: In March 2015, we updated previous searches (July 2008 and December 2013) of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, LILACS, CANCERLIT, clinical trials registries, conference proceedings, and references, without language restrictions. We also contacted experts for relevant published, unpublished and ongoing trials. Selection criteria: Randomised controlled trials (RCTs) of radiotherapy, surgery and corticosteroids in adults with MESCC. Data collection and analysis: Three authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. Where possible, we pooled relative risks with their 95% confidence intervals, using a random effects model if heterogeneity was significant. We assessed overall evidence-quality using the GRADE approach. Main results: This update includes seven trials involving 876 (723 evaluable) adult participants (19 to 87 years) in high-income countries. Most were free of the risk of bias. Different radiotherapy doses and schedulesTwo equivalence trials in people with MESCC and a poor prognosis evaluated different radiotherapy doses and schedules. In one, a single dose (8 Gray (Gy)) of radiotherapy (RT) was as effective as short-course RT (16 Gy in two fractions over one week) in enhancing ambulation in the short term (65% versus 69%; risk ratio (RR) was 0.93, (95% confidence interval (CI) 0.82 to 1.04); 303 participants; moderate quality evidence). The regimens were also equally effective in reducing analgesic and narcotic use (34% versus 40%; RR 0.85, 95% CI 0.62 to 1.16; 271 participants), and in maintaining urinary continence (90% versus 87%; RR 1.03, 95% CI 0.96 to 1.1; 303 participants) in the short term (moderate quality evidence). In the other trial, split-course RT (30 Gy in eight fractions over two weeks) was no different from short-course RT in enhancing ambulation (70% versus 68%; RR 1.02, 95% CI 0.9 to 1.15; 276 participants); reducing analgesic and narcotic use (49% versus 38%; RR 1.27, 95% CI 0.96 to 1.67; 262 participants); and in maintaining urinary continence (87% versus 90%; RR 0.97, 0.93 to 1.02; 275 participants) in the short term (moderate quality evidence). Median survival was similar with the three RT regimens (four months). Local tumour recurrence may be more common with single-dose compared to short-course RT (6% versus 3%; RR 2.21, 95% CI 0.69 to 7.01; 303 participants) and with short-course compared to split-course RT (4% versus 0%; RR 0.1, 95% CI 0.01 to 1.72; 276 participants), but these differences were not statistically significant (low quality evidence). Gastrointestinal adverse effects were infrequent with the three RT regimens (moderate quality evidence), and serious adverse events or post-radiotherapy myelopathy were not noted. We did not find trials comparing radiotherapy schedules in people with MESCC and a good prognosis. Surgery plus radiotherapy compared to radiotherapyLaminectomy plus RT offered no advantage over RT in one small trial with 29 participants (very low quality evidence). In another trial that was stopped early for apparent benefit, decompressive surgery plus RT resulted in better ambulatory rates (84% versus 57%; RR 1.48, 95% CI 1.16 to 1.90; 101 participants, low quality evidence). Narcotic use may also be lower, and bladder control may also be maintained longer than with than RT in selected patients (low quality evidence). Median survival was longer after surgery (126 days versus 100 days), but the proportions surviving at one month (94% versus 86%; RR 1.09, 95% CI 0.96 to 1.24; 101 participants) did not differ significantly (low quality evidence). Serious adverse events were not noted. Significant benefits with surgery occurred only in people younger than 65 years. High dose corticosteroids compared to moderate dose or no corticosteroidsData from three small trials suggest that high-dose steroids may not differ from moderate-dose or no corticosteroids in enhancing ambulation (60% versus 55%; RR 1.08, 95% CI 0.81 to 1.45; 3 RCTs, 105 participants); survival over two years (11% versus 10%; RR 1.11, 95% CI 0.24 to 5.05; 1 RCT, 57 participants); pain reduction (78% versus 91%; RR 0.86, 95% CI 0.62 to 1.20; 1 RCT, 25 participants); or urinary continence (63% versus 53%; RR 1.18, 95% CI 0.66 to 2.13; 1 RCT, 34 participants; low quality evidence). Serious adverse effects were more frequent with high-dose corticosteroids (17% versus 0%; RR 8.02, 95% CI 1.03 to 62.37; 2 RCTs, 77 participants; moderate quality evidence).None of the trials reported satisfaction with care or quality of life in participants. Authors' conclusions: Based on current evidence, ambulant adults with MESCC with stable spines and predicted survival of less than six months will probably benefit as much from one dose of radiation (8 Gy) as from two doses (16 Gy) or eight doses (30 Gy). We are unsure if a single dose is as effective as two or more doses in preventing local tumour recurrence. Laminectomy preceding radiotherapy may offer no benefits over radiotherapy alone. Decompressive surgery followed by radiotherapy may benefit ambulant and non-ambulant adults younger than 65 years of age, with poor prognostic factors for radiotherapy, a single area of compression, paraplegia for less than 48 hours, and a predicted survival of more than six months. We are uncertain whether high doses of corticosteroids offer any benefits over moderate doses or indeed no corticosteroids; but high-dose steroids probably significantly increases the risk of serious adverse effects. Early detection; and treatment based on neurological status, age and estimated survival, are crucial with all treatment modalities. Most of the evidence was of low quality. High-quality evidence from more trials is needed to clarify current uncertainties, and some studies are in progress.

The Cochrane database of systematic reviews · meta-analysis · 39 citationsread the source →

Comparison of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation before and during the COVID-19 pandemic: a systematic review and meta-analysis.

Background: There is a lack of consensus about the effect of the COVID-19 pandemic on the mental health of children and adolescents. We aimed to compare rates of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation during the pandemic with those before the pandemic. Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published between Jan 1, 2020, and Dec 19, 2022. Studies published in English with data on paediatric (ie, those aged <19 years) emergency department visits before and during the COVID-19 pandemic were included. Case studies and qualitative analyses were excluded. Changes in attempted suicide, self-harm, suicidal ideation, and other mental-illness indicators (eg, anxiety, depression, and psychosis) were expressed as ratios of the rates of emergency department visits during the pandemic compared with those before the pandemic, and we analysed these with a random-effects meta-analysis. This study was registered with PROSPERO, CRD42022341897. Findings: 10 360 non-duplicate records were retrieved, which yielded 42 relevant studies (with 130 sample-estimates) representing 11·1 million emergency department visits for all indications of children and adolescents across 18 countries. The mean age of the samples of children and adolescents across studies was 11·7 years (SD 3·1, range 5·5-16·3), and there were on average 57·6% girls and 43·4% boys as a proportion of emergency department visits for any health reasons (ie, physical and mental). Only one study had data related to race or ethnicity. There was good evidence of an increase in emergency department visits for attempted suicide during the pandemic (rate ratio 1·22, 90% CI 1·08-1·37), modest evidence of an increase in emergency department visits for suicidal ideation (1·08, 0·93-1·25), and good evidence for only a slight change in self-harm (0·96, 0·89-1·04). Rates of emergency department visits for other mental-illness indications showed very good evidence of a decline (0·81, 0·74-0·89), and paediatric visits for all health indications showed strong evidence of a reduction (0·68, 0·62-0·75). When rates for attempted suicide and suicidal ideation were combined as a single measure, there was good evidence of an increase in emergency department visits among girls (1·39, 1·04-1·88) and only modest evidence of an increase among boys (1·06, 0·92-1·24). Self-harm among older children (mean age 16·3 years, range 13·0-16·3) showed good evidence of an increase (1·18, 1·00-1·39), but among younger children (mean age 9·0 years, range 5·5-12·0) there was modest evidence of a decrease (0·85, 0·70-1·05). Interpretation: The integration of mental health support within community health and the education system-including promotion, prevention, early intervention, and treatment-is urgently needed to increase the reach of mental health support that can mitigate child and adolescent mental distress. In future pandemics, increased resourcing in some emergency department settings would help to address their expected increase in visits for acute mental distress among children and adolescents. Funding: None.

The lancet. Psychiatry · meta-analysis · 164 citationsread the source →

Index to predict 5-year mortality of community-dwelling adults aged 65 and older using data from the National Health Interview Survey.

Background: Prognostic information is becoming increasingly important for clinical decision-making. Objective: To develop and validate an index to predict 5-year mortality among community-dwelling older adults. Design and participants: A total of 24,115 individuals aged >65 who responded to the 1997-2000 National Health Interview Survey (NHIS) with follow-up through 31 December 2002 from the National Death Index; 16,077 were randomly selected for the development cohort and 8,038 for the validation cohort. Measurements: 39 risk factors (functional measures, illnesses, behaviors, demographics) were included in a multivariable Cox proportional hazards model to determine factors independently associated with mortality. Risk scores were calculated for participants using points derived from the final model's beta coefficients. To evaluate external validity, we compared survival by quintile of risk between the development and validation cohorts. Results: Seventeen percent of participants had died by the end of the study. The final model included 11 variables: age (1 point for 70-74 up to 7 points for >85); male: 3 points; BMI <25: 2 points; perceived health (good: 1 point, fair/poor: 2 points); emphysema: 2 points; cancer: 2 points; diabetes: 2 points; dependent in instrumental activities of daily living: 2 points; difficulty walking: 3 points; smoker-former: 1 point, smoker-current: 3 points; past year hospitalizations-one: 1 point, >2: 3 points. We observed close agreement between 5-year mortality in the two cohorts; which ranged from 5% in the lowest risk quintile to 50% in the highest risk quintile in the validation cohort. Conclusions: This validated mortality index can be used to account for participant life expectancy in analyses using NHIS data.

Journal of general internal medicine · randomised controlled trial · 166 citationsread the source →

Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis.

Background: Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause of patient dissatisfaction and may lead to prolonged hospital stay and higher costs of care along with more severe complications. Many antiemetic drugs are available for prophylaxis. They have various mechanisms of action and side effects, but there is still uncertainty about which drugs are most effective with the fewest side effects. Objectives: • To compare the efficacy and safety of different prophylactic pharmacologic interventions (antiemetic drugs) against no treatment, against placebo, or against each other (as monotherapy or combination prophylaxis) for prevention of postoperative nausea and vomiting in adults undergoing any type of surgery under general anaesthesia • To generate a clinically useful ranking of antiemetic drugs (monotherapy and combination prophylaxis) based on efficacy and safety • To identify the best dose or dose range of antiemetic drugs in terms of efficacy and safety SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and reference lists of relevant systematic reviews. The first search was performed in November 2017 and was updated in April 2020. In the update of the search, 39 eligible studies were found that were not included in the analysis (listed as awaiting classification). Selection criteria: Randomized controlled trials (RCTs) comparing effectiveness or side effects of single antiemetic drugs in any dose or combination against each other or against an inactive control in adults undergoing any type of surgery under general anaesthesia. All antiemetic drugs belonged to one of the following substance classes: 5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, corticosteroids, antihistamines, and anticholinergics. No language restrictions were applied. Abstract publications were excluded. Data collection and analysis: A review team of 11 authors independently assessed trials for inclusion and risk of bias and subsequently extracted data. We performed pair-wise meta-analyses for drugs of direct interest (amisulpride, aprepitant, casopitant, dexamethasone, dimenhydrinate, dolasetron, droperidol, fosaprepitant, granisetron, haloperidol, meclizine, methylprednisolone, metoclopramide, ondansetron, palonosetron, perphenazine, promethazine, ramosetron, rolapitant, scopolamine, and tropisetron) compared to placebo (inactive control). We performed network meta-analyses (NMAs) to estimate the relative effects and ranking (with placebo as reference) of all available single drugs and combinations. Primary outcomes were vomiting within 24 hours postoperatively, serious adverse events (SAEs), and any adverse event (AE). Secondary outcomes were drug class-specific side effects (e.g. headache), mortality, early and late vomiting, nausea, and complete response. We performed subgroup network meta-analysis with dose of drugs as a moderator variable using dose ranges based on previous consensus recommendations. We assessed certainty of evidence of NMA treatment effects for all primary outcomes and drug class-specific side effects according to GRADE (CINeMA, Confidence in Network Meta-Analysis). We restricted GRADE assessment to single drugs of direct interest compared to placebo. Main results: We included 585 studies (97,516 randomized participants). Most of these studies were small (median sample size of 100); they were published between 1965 and 2017 and were primarily conducted in Asia (51%), Europe (25%), and North America (16%). Mean age of the overall population was 42 years. Most participants were women (83%), had American Society of Anesthesiologists (ASA) physical status I and II (70%), received perioperative opioids (88%), and underwent gynaecologic (32%) or gastrointestinal surgery (19%) under general anaesthesia using volatile anaesthetics (88%). In this review, 44 single drugs and 51 drug combinations were compared. Most studies investigated only single drugs (72%) and included an inactive control arm (66%). The three most investigated single drugs in this review were ondansetron (246 studies), dexamethasone (120 studies), and droperidol (97 studies). Almost all studies (89%) reported at least one efficacy outcome relevant for this review. However, only 56% reported at least one relevant safety outcome. Altogether, 157 studies (27%) were assessed as having overall low risk of bias, 101 studies (17%) overall high risk of bias, and 327 studies (56%) overall unclear risk of bias. Vomiting within 24 hours postoperatively Relative effects from NMA for vomiting within 24 hours (282 RCTs, 50,812 participants, 28 single drugs, and 36 drug combinations) suggest that 29 out of 36 drug combinations and 10 out of 28 single drugs showed a clinically important benefit (defined as the upper end of the 95% confidence interval (CI) below a risk ratio (RR) of 0.8) compared to placebo. Combinations of drugs were generally more effective than single drugs in preventing vomiting. However, single NK₁ receptor antagonists showed treatment effects similar to most of the drug combinations. High-certainty evidence suggests that the following single drugs reduce vomiting (ordered by decreasing efficacy): aprepitant (RR 0.26, 95% CI 0.18 to 0.38, high certainty, rank 3/28 of single drugs); ramosetron (RR 0.44, 95% CI 0.32 to 0.59, high certainty, rank 5/28); granisetron (RR 0.45, 95% CI 0.38 to 0.54, high certainty, rank 6/28); dexamethasone (RR 0.51, 95% CI 0.44 to 0.57, high certainty, rank 8/28); and ondansetron (RR 0.55, 95% CI 0.51 to 0.60, high certainty, rank 13/28). Moderate-certainty evidence suggests that the following single drugs probably reduce vomiting: fosaprepitant (RR 0.06, 95% CI 0.02 to 0.21, moderate certainty, rank 1/28) and droperidol (RR 0.61, 95% CI 0.54 to 0.69, moderate certainty, rank 20/28). Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol showed clinically important benefit, but low doses showed no clinically important benefit. Aprepitant was used mainly at high doses, ramosetron at recommended doses, and fosaprepitant at doses of 150 mg (with no dose recommendation available). Frequency of SAEs Twenty-eight RCTs were included in the NMA for SAEs (10,766 participants, 13 single drugs, and eight drug combinations). The certainty of evidence for SAEs when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to low. Droperidol (RR 0.88, 95% CI 0.08 to 9.71, low certainty, rank 6/13) may reduce SAEs. We are uncertain about the effects of aprepitant (RR 1.39, 95% CI 0.26 to 7.36, very low certainty, rank 11/13), ramosetron (RR 0.89, 95% CI 0.05 to 15.74, very low certainty, rank 7/13), granisetron (RR 1.21, 95% CI 0.11 to 13.15, very low certainty, rank 10/13), dexamethasone (RR 1.16, 95% CI 0.28 to 4.85, very low certainty, rank 9/13), and ondansetron (RR 1.62, 95% CI 0.32 to 8.10, very low certainty, rank 12/13). No studies reporting SAEs were available for fosaprepitant. Frequency of any AE Sixty-one RCTs were included in the NMA for any AE (19,423 participants, 15 single drugs, and 11 drug combinations). The certainty of evidence for any AE when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to moderate. Granisetron (RR 0.92, 95% CI 0.80 to 1.05, moderate certainty, rank 7/15) probably has no or little effect on any AE. Dexamethasone (RR 0.77, 95% CI 0.55 to 1.08, low certainty, rank 2/15) and droperidol (RR 0.89, 95% CI 0.81 to 0.98, low certainty, rank 6/15) may reduce any AE. Ondansetron (RR 0.95, 95% CI 0.88 to 1.01, low certainty, rank 9/15) may have little or no effect on any AE. We are uncertain about the effects of aprepitant (RR 0.87, 95% CI 0.78 to 0.97, very low certainty, rank 3/15) and ramosetron (RR 1.00, 95% CI 0.65 to 1.54, very low certainty, rank 11/15) on any AE. No studies reporting any AE were available for fosaprepitant. Class-specific side effects For class-specific side effects (headache, constipation, wound infection, extrapyramidal symptoms, sedation, arrhythmia, and QT prolongation) of relevant substances, the certainty of evidence for the best and most reliable anti-vomiting drugs mostly ranged from very low to low. Exceptions were that ondansetron probably increases headache (RR 1.16, 95% CI 1.06 to 1.28, moderate certainty, rank 18/23) and probably reduces sedation (RR 0.87, 95% CI 0.79 to 0.96, moderate certainty, rank 5/24) compared to placebo. The latter effect is limited to recommended and high doses of ondansetron. Droperidol probably reduces headache (RR 0.76, 95% CI 0.67 to 0.86, moderate certainty, rank 5/23) compared to placebo. We have high-certainty evidence that dexamethasone (RR 1.00, 95% CI 0.91 to 1.09, high certainty, rank 16/24) has no effect on sedation compared to placebo. No studies assessed substance class-specific side effects for fosaprepitant. Direction and magnitude of network effect estimates together with level of evidence certainty are graphically summarized for all pre-defined GRADE-relevant outcomes and all drugs of direct interest compared to placebo in http://doi.org/10.5281/zenodo.4066353. Authors' conclusions: We found high-certainty evidence that five single drugs (aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron) reduce vomiting, and moderate-certainty evidence that two other single drugs (fosaprepitant and droperidol) probably reduce vomiting, compared to placebo. Four of the six substance classes (5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, and corticosteroids) were thus represented by at least one drug with important benefit for prevention of vomiting. Combinations of drugs were generally more effective than the corresponding single drugs in preventing vomiting. NK₁ receptor antagonists were the most effective drug class and had comparable efficacy to most of the drug combinations. 5-HT₃ receptor antagonists were the best studied substance class. For most of the single drugs of direct interest, we found only very low to low certainty evidence for safety outcomes such as occurrence of SAEs, any AE, and substance class-specific side effects. Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol were more effective than low doses for prevention of vomiting. Dose dependency of side effects was rarely found due to the limited number of studies, except for the less sedating effect of recommended and high doses of ondansetron. The results of the review are transferable mainly to patients at higher risk of nausea and vomiting (i.e. healthy women undergoing inhalational anaesthesia and receiving perioperative opioids). Overall study quality was limited, but certainty assessments of effect estimates consider this limitation. No further efficacy studies are needed as there is evidence of moderate to high certainty for seven single drugs with relevant benefit for prevention of vomiting. However, additional studies are needed to investigate potential side effects of these drugs and to examine higher-risk patient populations (e.g. individuals with diabetes and heart disease).

The Cochrane database of systematic reviews · systematic review · 127 citationsread the source →

Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors.

Background: Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. Objectives: To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women. Search methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events. Selection criteria: Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine). Data collection and analysis: We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2+], CIN grade 3 and above [CIN3+], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets. Main results: We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation. Efficacy endpoints by initial HPV DNA statushrHPV negativeHPV vaccines reduce CIN2+, CIN3+, AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2+ from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3+ from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82).HPV vaccines reduce the risk of any CIN2+ from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison.HPV16/18 negativeIn those aged 15 to 26 years, vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes. Vaccines reduce any CIN2+ from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions. Regardless of HPV DNA statusIn younger women HPV vaccines reduce the risk of CIN2+ associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3+ associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty).HPV vaccines reduce any CIN2+ from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)).In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.Adverse effectsThe risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established. Pregnancy outcomesAmong those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively). Authors' conclusions: There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status. We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.

The Cochrane database of systematic reviews · systematic review · 290 citationsread the source →

Predictors of illicit drug/s use among university students in Northern Ireland, Wales and England.

Introduction: The use of illicit drug/s among university students is a public health concern. Nevertheless, many UK studies investigated a narrow spectrum of variables to explore their association/s with illicit drug/s use. Methods: We assessed the associations between a wide range of socio-demographic, health and wellbeing variables (independent variables) and having used illicit drug/s regularly, occasionally or never in life (dependent variables). Data (3706 students) were collected from seven universities in England, Wales, and Northern Ireland, using a self-administered questionnaire. Results: About 5% of the sample had regularly used illicit drug/s, 25% occasionally, and 70% never. Regular drug use (RDU) was significantly more likely among males aged 21-29 years, daily smokers, those with heavy episodic drinking or possible alcohol dependency (CAGE test), and those who perceived their academic performance better than their peers. RDU was less likely among students with high health awareness and those living with parents. The predictors of occasional drug use (ODU) were similar to those of RDU. However, in addition, students with higher perceived stress were less likely, and students who felt financial burden/s were more likely to report ODU, while no association with academic performance was found. Never use of illicit drug/s was inversely associated with most of the variables listed above, and was positively associated with religiosity. Illicit drug/s use goes along with other substance use (alcohol and smoking). The finding that illicit drug/s use was higher among students reporting good academic performance was surprising and raises the question of whether illicit drug/s may be used as performance enhancing drugs. Conclusion: The factors identified with illicit drug/s use in this study could be utilized to develop appropriate public health policies and preventive measures for the health of students. Multilevel, value based, comprehensive, and strategic long-term intervention plans are required. This could include social interventions aimed at generating recreations alternatives and opportunities for youth, and a critical review for current authorities' interventions and services. Suggestions for coping with problems of campus illicit drug use/abuse also need to be offered.

Global journal of health science · 36 citationsread the source →

Prevalence of autism spectrum disorder among children aged 8 Years - Autism and developmental disabilities monitoring network, 11 Sites, United States, 2014

Problem/Condition: Autism spectrum disorder (ASD). Period Covered: 2014. Description of System: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system that provides estimates of the prevalence of autism spectrum disorder (ASD) among children aged 8 years whose parents or guardians reside within 11 ADDM sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). ADDM surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by professional service providers in the community. Staff completing record review and abstraction receive extensive training and supervision and are evaluated according to strict reliability standards to certify effective initial training, identify ongoing training needs, and ensure adherence to the prescribed methodology. Record review and abstraction occurs in a variety of data sources ranging from general pediatric health clinics to specialized programs serving children with developmental disabilities. In addition, most of the ADDM sites also review records for children who have received special education services in public schools. In the second phase of the study, all abstracted information is reviewed systematically by experienced clinicians to determine ASD case status. A child is considered to meet the surveillance case definition for ASD if he or she displays behaviors, as described on one or more comprehensive evaluations completed by community-based professional providers, consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for autistic disorder; pervasive developmental disorder-not otherwise specified (PDD-NOS, including atypical autism); or Asperger disorder. This report provides updated ASD prevalence estimates for children aged 8 years during the 2014 surveillance year, on the basis of DSM-IV-TR criteria, and describes characteristics of the population of children with ASD. In 2013, the American Psychiatric Association published the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which made considerable changes to ASD diagnostic criteria. The change in ASD diagnostic criteria might influence ADDM ASD prevalence estimates; therefore, most (85%) of the records used to determine prevalence estimates based on DSM-IV-TR criteria underwent additional review under a newly operationalized surveillance case definition for ASD consistent with the DSM-5 diagnostic criteria. Children meeting this new surveillance case definition could qualify on the basis of one or both of the following criteria, as documented in abstracted comprehensive evaluations: 1) behaviors consistent with the DSM-5 diagnostic features; and/or 2) an ASD diagnosis, whether based on DSM-IV-TR or DSM-5 diagnostic criteria. Stratified comparisons of the number of children meeting either of these two case definitions also are reported. Results: For 2014, the overall prevalence of ASD among the 11 ADDM sites was 16.8 per 1,000 (one in 59) children aged 8 years. Overall ASD prevalence estimates varied among sites, from 13.1-29.3 per 1,000 children aged 8 years. ASD prevalence estimates also varied by sex and race/ethnicity. Males were four times more likely than females to be identified with ASD. Prevalence estimates were higher for non-Hispanic white (henceforth, white) children compared with non-Hispanic black (henceforth, black) children, and both groups were more likely to be identified with ASD compared with Hispanic children. Among the nine sites with sufficient data on intellectual ability, 31% of children with ASD were classified in the range of intellectual disability (intelligence quotient [IQ] ≤ 70), 25% were in the borderline range (IQ 71-85), and 44% had IQ scores in the average to above average range (i.e., IQ > 85). The distribution of intellectual ability varied by sex and race/ethnicity. Although mention of developmental concerns by age 36 months was documented for 85% of children with ASD, only 42% had a comprehensive evaluation on record by age 36 months. The median age of earliest known ASD diagnosis was 52 months and did not differ significantly by sex or race/ethnicity. For the targeted comparison of DSM-IV-TR and DSM-5 results, the number and characteristics of children meeting the newly operationalized DSM-5 case definition for ASD were similar to those meeting the DSM-IV-TR case definition, with DSM-IV-TR case counts exceeding DSM-5 counts by less than 5% and approximately 86% overlap between the two case definitions (kappa = 0.85). Interpretation: Findings from the ADDM Network, on the basis of 2014 data reported from 11 sites, provide updated populationbased estimates of the prevalence of ASD among children aged 8 years in multiple communities in the United States. The overall ASD prevalence estimate of 16.8 per 1,000 children aged 8 years in 2014 is higher than previously reported estimates from the ADDM Network. Because the ADDM sites do not provide a representative sample of the entire United States, the combined prevalence estimates presented in this report cannot be generalized to all children aged 8 years in the United States. Consistent with reports from previous ADDM surveillance years, findings from 2014 were marked by variation in ASD prevalence when stratified by geographic area, sex, and level of intellectual ability. Differences in prevalence estimates between black and white children have diminished in most sites, but remained notable for Hispanic children. For 2014, results from application of the DSM-IV-TR and DSM-5 case definitions were similar, overall and when stratified by sex, race/ethnicity, DSM-IV-TR diagnostic subtype, or level of intellectual ability. Public Health Action: Beginning with surveillance year 2016, the DSM-5 case definition will serve as the basis for ADDM estimates of ASD prevalence in future surveillance reports. Although the DSM-IV-TR case definition will eventually be phased out, it will be applied in a limited geographic area to offer additional data for comparison. Future analyses will examine trends in the continued use of DSM-IV-TR diagnoses, such as autistic disorder, PDD-NOS, and Asperger disorder in health and education records, documentation of symptoms consistent with DSM-5 terminology, and how these trends might influence estimates of ASD prevalence over time. The latest findings from the ADDM Network provide evidence that the prevalence of ASD is higher than previously reported estimates and continues to vary among certain racial/ethnic groups and communities. With prevalence of ASD ranging from 13.1 to 29.3 per 1,000 children aged 8 years in different communities throughout the United States, the need for behavioral, educational, residential, and occupational services remains high, as does the need for increased research on both genetic and nongenetic risk factors for ASD.

UNC Libraries · 1381 citationsread the source →

Adherence to physical activity guidelines in older adults, using objectively measured physical activity in a population-based study.

Background: Physical activity (PA) levels in older adults decline with age. The prevalence and correlates of adherence to current UK PA guidelines in older adults has not been studied using objectively measured PA, which can examine precisely whether PA is carried out in bouts of specified length and intensity. Methods: Free living men and women aged 70-93 years from 25 towns in the United Kingdom, participating in parallel on-going population based cohort studies were invited (by post) to wear a GT3x accelerometer over the hip for one week in 2010-12. Adherence to UK PA guidelines was defined as ≥150 minutes/week of moderate or vigorous PA (MVPA) in bouts of ≥10 minutes; the effect of different intensities and durations were examined. Results: 1593 men and 857 women participated (responses 51% and 29% respectively). 15% men and 10% women achieved ≥150 minutes/week of MVPA (defined as >1040 cpm) in bouts lasting ≥10 minutes. With MVPA defined as >1952 cpm, prevalences were 7% and 3% respectively. Those adhering to guidelines were younger, had fewer chronic health conditions, less depression, less severe mobility limitations, but higher exercise self-efficacy and exercise outcomes expectations. They rated their local environment more highly for social activities and leisure facilities, having somewhere nice to go for a walk and feeling safe after dark, They left the house on more days per week, were more likely to use active transport (cycle or walk) and to walk a dog regularly. Conclusions: Few older adults attain current PA guidelines. Health promotion to extend the duration of moderate-intensity activity episodes to 10 minutes or more could yield important health gains among older adults. However future studies will need to clarify whether attaining guideline amounts of PA in spells lasting 10 minutes or more is critical for reducing chronic disease risks as well as improving cardiometabolic risk factors.

BMC public health · 185 citationsread the source →

Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial.

Background: Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. Methods: In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab. Eligible patients were aged 18-80 years, had active Crohn's disease of the terminal ileum, and had not responded to at least 3 months of conventional therapy with glucocorticosteroids, thiopurines, or methotrexate. Patients with diseased terminal ileum longer than 40 cm or abdominal abscesses were excluded. The primary outcome was quality of life on the Inflammatory Bowel Disease Questionnaire (IBDQ) at 12 months. Secondary outcomes were general quality of life, measured by the Short Form-36 (SF-36) health survey and its physical and mental component subscales, days unable to participate in social life, days on sick leave, morbidity (additional procedures and hospital admissions), and body image and cosmesis. Analyses of the primary outcome were done in the intention-to-treat population, and safety analyses were done in the per-protocol population. This trial is registered at the Dutch Trial Registry (NTR1150). Findings: Between May 2, 2008, and October 14, 2015, 73 patients were allocated to have resection and 70 to receive infliximab. Corrected for baseline differences, the mean IBDQ score at 12 months was 178·1 (95% CI 171·1-185·0) in the resection group versus 172·0 (164·3-179·6) in the infliximab group (mean difference 6·1 points, 95% CI -4·2 to 16·4; p=0·25). At 12 months, the mean SF-36 total score was 112·1 (95% CI 108·0-116·2) in the resection group versus 106·5 (102·1-110·9) in the infliximab group (mean difference 5·6, 95% CI -0·4 to 11·6), the mean physical component score was 47·7 (45·7-49·7) versus 44·6 (42·5-46·8; mean difference 3·1, 4·2 to 6·0), and the mean mental component score was 49·5 (47·0-52·1) versus 46·1 (43·3-48·9; mean difference 3·5, -0·3 to 7·3). Mean numbers of days of sick leave were 3·4 days (SD 7·1) in the resection group versus 1·4 days (4·7) in the infliximab group (p<0·0001), days not able to take part in social life were 1·8 days (6·3) versus 1·1 days (4·5; p=0·20), days of scheduled hospital admission were 6·5 days (3·8) versus 6·8 days (3·2; p=0·84), and the number of patients who had unscheduled hospital admissions were 13 (18%) of 73 versus 15 (21%) of 70 (p=0·68). Body-image scale mean scores in the patients who had resection were 16·0 (95% CI 15·2-16·8) at baseline versus 17·8 (17·1-18·4) at 12 months, and cosmetic scale mean scores were 17·6 (16·6-18·6) versus 18·6 (17·6-19·6). Surgical intervention-related complications classified as IIIa or worse on the Clavien-Dindo scale occurred in four patients in the resection group. Treatment-related serious adverse events occurred in two patients in the infliximab group. During a median follow-up of 4 years (IQR 2-6), 26 (37%) of 70 patients in the infliximab group had resection, and 19 (26%) of 73 patients in the resection group received anti-TNF. Interpretation: Laparoscopic resection in patients with limited (diseased terminal ileum <40 cm), non-stricturing, ileocaecal Crohn's disease in whom conventional therapy has failed could be considered a reasonable alternative to infliximab therapy. Funding: Netherlands Organisation for Health Research and Development.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 228 citationsread the source →

Effect of Denosumab or Alendronic Acid on the Progression of Aortic Stenosis: A Double-Blind Randomized Controlled Trial.

Background: Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic differentiation of valvular interstitial cells are important contributory mechanisms. We aimed to establish whether inhibition of these pathways with denosumab or alendronic acid could reduce disease progression in aortic stenosis. Methods: In a single-center, parallel group, double-blind randomized controlled trial, patients >50 years of age with calcific aortic stenosis (peak aortic jet velocity >2.5 m/s) were randomized 2:1:2:1 to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly), or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and 18F-sodium fluoride positron emission tomography and computed tomography. The primary end point was the calculated 24-month change in aortic valve calcium score. Results: A total of 150 patients (mean age, 72±8 years; 21% women) with calcific aortic stenosis (peak aortic jet velocity, 3.36 m/s [2.93-3.82 m/s]; aortic valve calcium score, 1152 AU [655-2065 AU]) were randomized and received the allocated trial intervention: denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25; pooled for analysis). Serum C-terminal telopeptide, a measure of bone turnover, halved from baseline to 6 months with denosumab (0.23 [0.18-0.33 µg/L] to 0.11 µg/L [0.08-0.17 µg/L]) and alendronic acid (0.20 [0.14-0.28 µg/L] to 0.09 µg/L [0.08-0.13 µg/L]) but was unchanged with placebo (0.23 [0.17-0.30 µg/L] to 0.26 µg/L [0.16-0.31 µg/L]). There were no differences in 24-month change in aortic valve calcium score between denosumab and placebo (343 [198-804 AU] versus 354 AU [76-675 AU]; P=0.41) or alendronic acid and placebo (326 [138-813 AU] versus 354 AU [76-675 AU]; P=0.49). Similarly, there were no differences in change in peak aortic jet velocity or 18F-sodium fluoride aortic valve uptake. Conclusions: Neither denosumab nor alendronic acid affected progression of aortic valve calcification in patients with calcific aortic stenosis. Alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with this potentially fatal condition. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

Circulation · randomised controlled trial · 126 citationsread the source →

Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

Background: Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. Methods: We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Findings: Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroconversion to type 1 poliovirus were 166 (98·8%) of 168, 95% CI 95·8-99·7; 178 (100%), 97·9-100·0; and 175 (100%), 97·9-100·0. Proportions with seroconvsion to type 3 poliovirus were 163 (98·2%) of 166, 94·8-99·4; 177 (100%), 97·9-100·0, and 172 (98·9%) of 174, 95·9-99·7. Non-inferiority was thus shown for the bOPV-containing schedules compared with the all-IPV schedule, with no significant differences between groups. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroprotective antibody titres to type 1 poliovirus were 168 (98·8%) of 170, 95% CI 95·8-99·7; 181 (100%), 97·9-100·0; and 177 (100%), 97·9-100·0. Proportions to type 3 poliovirus were 166 (98·2%) of 169, 94·9-99·4; 180 (100%), 97·9-100·0; and 174 (98·9%) of 176, 96·0-99·7. Non-inferiority comparisons could not be done for this outcome because median titres for the groups receiving OPV were greater than the assay's upper limit of detection (log2 titres >10·5). The proportions of children seroconverting to type 2 poliovirus in the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, were 130 (77·4%) of 168, 95% CI 70·5-83·0; 169 (96·0%) of 176, 92·0-98·0; and 175 (100%), 97·8-100. IPV-bOPV schedules resulted in almost a 0·3 log reduction of type 2 faecal shedding compared with the IPV-only schedule. No participants died during the trial; 81 serious adverse events were reported, of which one was thought to be possibly vaccine-related (intestinal intussusception). Interpretation: Seroconversion rates against polioviruses types 1 and 3 were non-inferior in sequential schedules containing IPV and bOPV, compared with an all-IPV schedule, and proportions of infants with protective antibodies were high after all three schedules. One or two doses of bOPV after IPV boosted intestinal immunity for poliovirus type 2, suggesting possible cross protection. Additionally, there was evidence of humoral priming for type 2 from one dose of IPV. Our findings could give policy makers flexibility when choosing a vaccination schedule, especially when trying to eliminate vaccine-associated and vaccine-derived poliomyelitis. Funding: Bill & Melinda Gates Foundation.

The Lancet. Infectious diseases · randomised controlled trial · 60 citationsread the source →

Online positive-oriented counseling, taking vitamin D3 tablet, online lifestyle modification training on premenstrual syndrome: a 3-armed randomized clinical trial.

Lack of absolute treatment for premenstrual syndrome (PMS), its cyclic nature, considerable prevalence (70-90%), and its mental and physical burden imply necessity of effectiveness comparison of various treatments. Although antidepressant and hormonal drugs are well-known medications for PMS, in affected women who can't tolerate, or don't have compatibility or compliance with these drugs, other effective treatments have always been important concern. This study aimed to compare effectiveness of online positive-oriented counseling, taking vitamin D3 tablet, and online lifestyle modification training on alleviating PMS. 3-armed parallel randomized clinical trial was performed on 84 20-40-year-old eligible women with PMS. 84 women were randomly ( www.random.org/sequenc ) allocated into three groups, but data of 77 women (1, n = 25) online positive-oriented counseling group (6 sessions), (2, n = 27) vitamin D3 tablet group (one vitamin D3 tablet weekly for 6 weeks), and (3, n = 25) online lifestyle training group (6 sessions) were analyzed. Vitamin D3 was measured at baseline, week6 and fallow up week10. Primary outcome variable PMS was measured with Premenstrual Symptoms Screening Tool (PSST) at baseline, week 6, and follow-up week 10. Primary outcome satisfaction with intervention method was measured using satisfaction scale at week 6 and follow-up week 10. ANOVA, Repeated Measures, and Paired samples t-test were used for statistical analysis. There was no statistically significant difference in PMS at baseline between three groups respectively (33 ± 5.8, 34.1 ± 7.1, & 35.2 ± 6.4, P = 0.500). However, at follow-up week 10, there was statistically significant difference between three groups (22.3 ± 4.3, 25.4 ± 6.5, & 31.8 ± 6.5; P < 0.001), with greatest improvement in online positive-oriented counseling group (P < 0.001). Satisfaction differed significantly among three groups at week 6 (51 ± 6.8, 46.4 ± 12, & 42.3 ± 6.3, P = 0.001) and follow-up week 10 (55.7 ± 11.6, 51.4 ± 12; & 43 ± 3.3, P < 0.001), with most satisfaction in positive-oriented counseling group (P < 0.001). All three interventions alleviated PMS, but online positive-oriented counseling was more effective and satisfying. Superiority of positive-oriented counseling implies mechanism of adaptation, better relationships, forgiveness, self-mood-regulation, and feasibility of its skills that could be continued individually by women after counseling completion. It is recommended health providers, health policymakers and managers support use of these interventions in treatment program and clinical guidelines. Trial registration: RCT registration number: IRCT20191231045967N1, Registration date:11/02/2020, Registration timing: prospective (IRCT | Survey the effect of vitamin D3 tablet intake, positivism group consulting with changing in life style in the treatment of premenstrual syndrome in women).

Scientific reports · randomised controlled trial · 4 citationsread the source →

Effects of supervised exercise training during pregnancy on psychological well-being among overweight and obese women: secondary analyses of the ETIP-trial, a randomised controlled trial.

Objectives: Women with high body mass index (BMI) have increased risk for symptoms of anxiety and depression during pregnancy and postpartum. In this prespecified secondary analysis from the exercise training in pregnancy trial, our aim was to examine effects of supervised exercise during pregnancy on psychological well-being in late pregnancy and postpartum among women with a prepregnancy BMI ≥28 kg/m2. Design: Single-centre, parallel group, randomised controlled trial. Setting: University Hospital, Norway. Participants: Ninety-one women (age 31.2±4.1 years, BMI 34.5±4.2 kg/m2), 46 in the exercise group, 45 in the control group, were included in the trial. Intervention: The exercise group was offered 3 weekly supervised exercise sessions (35 min of moderate intensity walking/running and 25 min of resistance training), until delivery. Primary and secondary outcomes measures: Primary analyses were based on intention to treat, with secondary perprotocol analyses. To assess psychological well-being, we used the 'Psychological General Well-Being Index' (PGWBI) at inclusion (gestational week 12-18), late pregnancy (gestational week 34-37) and 3 months postpartum. We assessed postpartum depression using the 'Edinburgh Postnatal Depression Scale' (EPDS). Results: Numbers completed data collection: late pregnancy 72 (exercise 38, control 36), postpartum 70 (exercise 36, control 34). In the exercise group, 50% adhered to the exercise protocol. Baseline PGWBI for all women was 76.4±12.6. Late pregnancy PGWBI; exercise 76.6 (95% CI 72.2 to 81.0), control 74.0 (95% CI 69.4 to 78.5) (p=0.42). Postpartum PGWBI; exercise 85.4 (95% CI 81.9 to 88.8), control 84.6 (95% CI 80.8 to 88.4) (with no between-group difference, p=0.77). There was no between-group difference in EPDS; exercise 2.96 (95% CI 1.7 to 4.2), control 3.48 (95% CI 2.3 to 4.7) (p=0.55). Conclusions: We found no effect of supervised exercise during pregnancy on psychological well-being among women with high BMI. Our findings may be hampered by low adherence to the exercise protocol. Trial registration number: NCT01243554.

BMJ open · randomised controlled trial · 16 citationsread the source →

Cancer and aging: Reflections for elders- Expressive writing intervention: A pilot study.

Objectives: The Cancer and Aging: Reflections for Elders Expressive Writing Intervention (CARE-Express) was developed to enhance coping and minimize psychological distress in older adults with cancer. The aim of the current study is to evaluate the feasibility and initial efficacy of CARE-Express. Materials and methods: Seventy-one distressed older adults (≥70) with cancer were assigned to CARE-Express (n = 41) or the Enhanced Social Work Control (ESWC) arm (n = 30). Participants completed five telephone sessions over seven weeks and were assessed on psychosocial variables at baseline, post-intervention, and four months post study enrollment. Feasibility was assessed by examining rates of eligibility, acceptance, retention, assessment, and fidelity. Initial efficacy was evaluated using standardized effect sizes. Results: Adequate rates of acceptance (29%), eligibility (66%), retention (90%), assessment (70% at post-intervention, 63% at four month follow-up), and fidelity (97%) were observed. At post-intervention, participants receiving CARE-Express reported less depression compared to ESWC (d = 0.69, p = 0.01) and lower demoralization (d = 0.50, p = 0.06). A small/moderate effect was demonstrated for increased total spirituality scores (d = 0.41, p = 0.07), meaning/peace (d = 0.32, p = 0.20) and faith (d = 0.35, p = 0.07). The CARE-Express group reported greater reductions in behavioral disengagement (d = 0.44, p = 0.06), while ESWC demonstrated a small effect for active coping (d = 0.21, p = 0.31). At four months, differential effects of CARE-Express had attenuated, though small/moderate, effects in favor of CARE-Express remained. Conclusion: Results support the feasibility of CARE-Express and its potential positive impact on psychological well-being. Trial registration: Registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT00984321 on September 25, 2009.

Journal of geriatric oncology · randomised controlled trial · 7 citationsread the source →

A telehealth lifestyle intervention to reduce excess gestational weight gain in pregnant women with overweight or obesity (GLOW): a randomised, parallel-group, controlled trial.

Background: Excess gestational weight gain (GWG) among women with overweight or obesity synergistically increases their already elevated risk of having gestational diabetes, a caesarean delivery, a large for gestational age infant, and post-partum weight retention, and increases their child's risk of obesity. We investigated whether a primarily telehealth lifestyle intervention reduced excess GWG among women with overweight or obesity. Methods: We did a randomised controlled trial in five antenatal clinics of Kaiser Permanente; Oakland, San Leandro, Walnut Creek, Fremont, and Santa Clara, CA, USA. Women at 8-15 weeks' gestation with singletons, pre-pregnancy BMI 25·0-40·0 kg/m2, and aged 18 years or older were randomly assigned (1:1) to receive the telehealth lifestyle intervention or usual antenatal care. Randomisation was adaptively balanced for age, BMI, and race and ethnicity. Data collectors and investigators were masked to group assignments. The core lifestyle intervention consisted of two in-person and 11 telephone sessions on behavioural strategies to improve weight, diet, and physical activity, and stress management to help women meet a trial goal of gaining at the lower limit of the Institute of Medicine (IOM) guidelines range for total GWG: 7 kg for women with overweight and 5 kg for women with obesity. Usual antenatal care included an antenatal visit at 7-10 weeks' gestation, an additional seven antenatal visits, on average, and periodic health education newsletters, including the IOM GWG guidelines and information on healthy eating and physical activity in pregnancy. The primary outcome was weekly rate of GWG expressed as excess GWG, per Institute of Medicine guidelines and mean assessed in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT02130232. Findings: Between March 24, 2014, and Sept 26, 2017, 5329 women were assessed for eligibility and 200 were randomly assigned to the lifestyle intervention group and 198 to the usual care group. Analyses included 199 women in the lifestyle intervention group (one lost to follow-up) and 195 in the usual care group (three lost to follow-up). 96 (48%) women in the lifestyle intervention group and 134 (69%) women in the usual care group exceeded Institute of Medicine guidelines for rate of GWG per week (relative risk 0·70, 95% CI 0·59 to 0·83). Compared with usual care, women in the lifestyle intervention had reduced weekly rate of GWG (mean 0·26 kg per week [SD 0·15] vs 0·32 kg per week [0·13]; mean between-group difference -0·07 kg per week, 95% CI -0·09 to -0·04). No between-group differences in perinatal complications were observed. Interpretation: Our evidence-based programme showed that health-care delivery systems could further adapt to meet the needs of their clinical settings to prevent excess GWG and improve healthy behaviours and markers of insulin resistance among women with overweight or obesity by using telehealth lifestyle interventions. Funding: US National Institutes of Health.

The lancet. Diabetes & endocrinology · randomised controlled trial · 122 citationsread the source →

Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial.

Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing. Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014. Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32]). Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents. Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office.

Lancet (London, England) · randomised controlled trial · 121 citationsread the source →

Susceptibility of interstitial continuous glucose monitor performance to sleeping position.

Background: Developing a round-the-clock artificial pancreas requires accurate and stable continuous glucose monitoring. The most widely used continuous glucose monitors (CGMs) are percutaneous, with the sensor residing in the interstitial space. Inaccuracies in percutaneous CGM readings during periods of lying on the devices (e.g., in various sleeping positions) have been anecdotally reported but not systematically studied. Methods: In order to assess the impact of sleep and sleep position on CGM performance, we conducted a study in human subjects in which we measured the variability of interstitial CGM data at night as a function of sleeping position. Commercially available sensors were placed for 4 days in the abdominal subcutaneous tissue in healthy, nondiabetic volunteers (four sensors per person, two per side). Nocturnal sleeping position was determined from video recordings and correlated to sensor data. Results: We observed that, although the median of the four sensor readings was typically 70-110 mg/dl during sleep, individual sensors intermittently exhibited aberrant glucose readings (>25 mg/dl away from median) and that these aberrant readings were strongly correlated with subjects lying on the sensors. We expected and observed that most of these aberrant sleep-position-related CGM readings were sudden decreases in reported glucose values, presumably due to local blood-flow decreases caused by tissue compression. Curiously, in rare cases, the aberrant CGM readings were elevated values. Conclusions: These findings highlight limitations in our understanding of interstitial fluid physiology in the subcutaneous space and have significant implications for the utilization of sensors in the construction of an artificial pancreas.

Journal of diabetes science and technology · clinical trial · 65 citationsread the source →

Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial.

Background: Patients with advanced cancer have reduced quality of life, which tends to worsen towards the end of life. We assessed the effect of early palliative care in patients with advanced cancer on several aspects of quality of life. Methods: The study took place at the Princess Margaret Cancer Centre (Toronto, ON, Canada), between Dec 1, 2006, and Feb 28, 2011. 24 medical oncology clinics were cluster randomised (in a 1:1 ratio, using a computer-generated sequence, stratified by clinic size and tumour site [four lung, eight gastrointestinal, four genitourinary, six breast, two gynaecological]), to consultation and follow-up (at least monthly) by a palliative care team or to standard cancer care. Complete masking of interventions was not possible; however, patients provided written informed consent to participate in their own study group, without being informed of the existence of another group. Eligible patients had advanced cancer, European Cooperative Oncology Group performance status of 0-2, and a clinical prognosis of 6-24 months. Quality of life (Functional Assessment of Chronic Illness Therapy--Spiritual Well-Being [FACIT-Sp] scale and Quality of Life at the End of Life [QUAL-E] scale), symptom severity (Edmonton Symptom Assessment System [ESAS]), satisfaction with care (FAMCARE-P16), and problems with medical interactions (Cancer Rehabilitation Evaluation System Medical Interaction Subscale [CARES-MIS]) were measured at baseline and monthly for 4 months. The primary outcome was change score for FACIT-Sp at 3 months. Secondary endpoints included change score for FACIT-Sp at 4 months and change scores for other scales at 3 and 4 months. This trial is registered with ClinicalTrials.gov, number NCT01248624. Findings: 461 patients completed baseline measures (228 intervention, 233 control); 393 completed at least one follow-up assessment. At 3-months, there was a non-significant difference in change score for FACIT-Sp between intervention and control groups (3·56 points [95% CI -0·27 to 7·40], p=0·07), a significant difference in QUAL-E (2·25 [0·01 to 4·49], p=0·05) and FAMCARE-P16 (3·79 [1·74 to 5·85], p=0·0003), and no difference in ESAS (-1·70 [-5·26 to 1·87], p=0·33) or CARES-MIS (-0·66 [-2·25 to 0·94], p=0·40). At 4 months, there were significant differences in change scores for all outcomes except CARES-MIS. All differences favoured the intervention group. Interpretation: Although the difference in quality of life was non-significant at the primary endpoint, this trial shows promising findings that support early palliative care for patients with advanced cancer. Funding: Canadian Cancer Society, Ontario Ministry of Health and Long Term Care.

Lancet (London, England) · randomised controlled trial · 1215 citationsread the source →

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial.

Background: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option for oligometastatic prostate cancer. However, limited prospective evidence is available. Objective: To determine the safety and feasibility of single fraction SABR for patients with oligometastatic prostate cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity, quality of life (QoL), and prostate-specific antigen response. Design, setting, and participants: In a prospective clinical trial, patients were screened with computed tomography, bone scan, and sodium fluoride positron emission tomography scan and had one to three oligometastases. Kaplan-Meier methods were used to determine LPFS and DPFS. Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. QoL was assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-BM22 at 1, 3,12, and 24 mo. Intervention: A single fraction of 20-Gy SABR to each lesion. Results and limitations: Between 2013 and 2014, 33 consecutive patients received SABR to a total of 50 oligometastases and were followed for 2 yr. The median age was 70 yr. The Gleason score was ≥8 in 15 patients (45%). Twenty patients had bone only, 12 had node only, and one had mixed disease. SABR was feasible and delivered as planned in 97% of cases. There was one grade 3 adverse event (3.0%, vertebral fracture). No patient died. The 1 and 2-yr LPFS was 97% (95% confidence interval [CI]: 91-100) and 93% (95% CI: 84-100), and DPFS was 58% (95% CI: 43-77) and 39% (95% CI: 25-60), respectively. In those not on androgen deprivation therapy (ADT; n=22), the 2-yr freedom from ADT was 48%. There was no significant difference from baseline QoL observed. Limitations include small sample size, limited duration of follow-up, and lack of a control arm. Conclusions: A single SABR session was feasible and associated with low morbidity in this cohort. Over one-third of patients did not progress and were free from ADT at 2-yr. QoL measures were maintained with this treatment strategy. Patient summary: This clinical trial investigated single treatment stereotactic radiotherapy for low volume advanced prostate cancer. The approach was found to be safe with avoidance of hormone therapy in almost half of the participants at 2 yr.

European urology · clinical trial · 222 citationsread the source →

Annual high-dose vitamin D3 and mental well-being: randomised controlled trial.

Background: Epidemiological evidence supports a relationship between vitamin D and mental well-being, although evidence from large-scale placebo-controlled intervention trials is lacking. Aims: To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms; and if there is an association between serum 25-hydroxyvitamin D levels and mental health. Method: A double-blind, randomised, placebo-controlled trial of women aged 70 or older (the Vital D Study: ISRCTN83409867 and ACTR12605000658617). Participants were randomly assigned to receive 500 000 IU vitamin D(3) (cholecalciferol) orally or placebo every autumn/winter for 3-5 consecutive years. The tools utilised at various time points were the General Health Questionnaire, the 12-item Short Form Health Survey, the Patient Global Impression-Improvement scale and the WHO Well-Being Index. Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants. Results: In this non-clinical population, no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health. Serum 25-hydroxyvitamin D levels in the vitamin D group were 41% higher than the placebo group 12 months following their annual dose. Despite this difference, scores from the questionnaires did not differ. Furthermore, there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups. Conclusions: The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3) is a practical intervention to prevent depressive symptoms in older community-dwelling women.

The British journal of psychiatry : the journal of mental science · randomised controlled trial · 111 citationsread the source →

Virtual reality exposure therapy and standard (in vivo) exposure therapy in the treatment of fear of flying.

This controlled clinical trial tested virtual reality exposure (VRE) therapy for the fear of flying (FOF), a relatively new and innovative way to do exposure therapy, and compared it to standard (in vivo) exposure therapy (SE) and a wait list (WL) control with a 6- and 12-month follow-up. Eighty-three participants with FOF were randomly assigned to VRE, SE, or WL. Seventy-five participants, 25 per group, completed the study. Twenty-three WL participants completed randomly assigned treatment following the waiting period. Treatment consisted of 4 sessions of anxiety management training followed either by exposure to a virtual airplane (VRE) or an actual airplane at the airport (SE) conducted over 6 weeks. Results indicate that VRE was superior to WL on all measures, including willingness to fly on the posttreatment flight (76% for VRE and SE; 20% for WL). VRE and SE were essentially equivalent on standardized questionnaires, willingness to fly, anxiety ratings during the flight, self-ratings of improvement, and patient satisfaction with treatment. Follow-up assessments at 6 and 12 months indicated that treatment gains were maintained, with more than 70% of respondents from both groups reporting continued flying at follow-up. Based on these findings, the use of VRE in the treatment of FOF was supported in this controlled study, suggesting that experiences in the virtual world can change experiences in the real world.

Behavior therapy · randomised controlled trial · 90 citationsread the source →

Cost-effectiveness and safety of epidural steroids in the management of sciatica.

Objectives: To investigate the clinical effectiveness of epidural steroid injections (ESIs) in the treatment of sciatica with an adequately powered study and to identify potential predictors of response to ESIs. Also, to investigate the safety and cost-effectiveness of lumbar ESIs in patients with sciatica. Design: A pragmatic, prospective, multicentre, double-blind, randomised, placebo-controlled trial with 12-month follow-up was performed. Patients were stratified according to acute (<4 months since onset) versus chronic (4-18 months) presentation. All analyses were performed on an intention-to-treat basis with last observation carried forward used to impute missing data. Setting: Rheumatology, orthopaedic and pain clinics in four participating centres: three district hospitals and one teaching hospital in the south of England. Participants: Total of 228 patients listed for ESI with clinically diagnosed unilateral sciatica, aged between 18 and 70 years, who had a duration of symptoms between 4 weeks and 18 months. Interventions: Patients received up to three injections of epidural steroid and local anaesthetic (active), or an injection of normal saline into the interspinous ligament (placebo). Main outcome measures: The primary outcome measure was the Oswestry Disability Questionnaire (ODQ); measures of pain relief and psychological and physical function were collected. Health economic data on return to work, analgesia use and other interventions were also measured. Quality-adjusted life-years (QALYs) were calculated using the SF-6D, calculated from the Short Form (SF-36). Costs per patient were derived from figures supplied by the centres' finance departments and a costings exercise performed as part of the study. A cost-utility analysis was performed using the SF-36 to calculate costs per QALY. Results: ESI led to a transient benefit in ODQ and pain relief, compared with placebo at 3 weeks (p = 0.017, number needed to treat = 11.4). There was no benefit over placebo between weeks 6 and 52. Using incremental QALYs, this equates to and additional 2.2 days of full health. Acute sciatica seemed to respond no differently to chronic sciatica. There were no significant differences in any other indices, including objective tests of function, return to work or need for surgery at any time-points. There were no clinical predictors of response, although the trial lacked sufficient power to be confident of this. Adverse events were uncommon, with no difference between groups. Costs per QALY to providers under the trial protocol were 44,701 pounds sterling. Costs to the purchaser per QALY were 354,171 pounds sterling. If only one ESI was provided then costs per QALY fell to 25,745 pounds sterling to the provider and 167,145 pounds sterling to the purchaser. ESIs thus failed the QALY threshold recommended by the National Institute for Health and Clinical Excellence (NICE). Conclusions: Although ESIs appear relatively safe, it was found that they confer only transient benefit in symptoms and self-reported function in a small group of patients with sciatica at substantial costs. ESIs do not provide good value for money if NICE recommendations are followed. Additional research is suggested into the epidemiology of radicular pain, producing a register of all ESIs, possible subgroups who may benefit from ESIs, the use of radiological imaging, optimal early interventions, analgesic agents and nerve root injections, the use of cognitive behavioural therapy in rehabilitation, improved methods of assessment, a comparative cost-utility analysis between various treatment strategies, and methods to reduce the effect of scarring and inflammation.

Health technology assessment (Winchester, England) · randomised controlled trial · 72 citationsread the source →

Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer.

Purpose: For patients with small-cell lung cancer (SCLC), further chemotherapy is routinely considered at relapse after first-line therapy. However, proof of clinical benefit has not been documented. Patients and methods: This study randomly assigned patients with relapsed SCLC not considered as candidates for standard intravenous therapy to best supportive care (BSC) alone (n = 70) or oral topotecan (2.3 mg/m2/d, days 1 through 5, every 21 days) plus BSC (topotecan; n = 71). Results: In the intent-to-treat population, survival (primary end point) was prolonged in the topotecan group (log-rank P = .0104). Median survival with BSC was 13.9 weeks (95% CI, 11.1 to 18.6) and with topotecan, 25.9 weeks (95% CI, 18.3 to 31.6). Statistical significance for survival was maintained in a subgroup of patients with a short treatment-free interval (< or = 60 days). Response to topotecan was 7% partial and 44% stable disease. Patients on topotecan had slower quality of life deterioration and greater symptom control. Principal toxicities with topotecan were hematological: grade 4 neutropenia, 33%; grade 4 thrombocytopenia, 7%; and grade 3/4 anemia, 25%. Comparing topotecan with BSC, infection grade 2 was 14% versus 12% and sepsis 4% versus 1%; other grade 3/4 events included vomiting 3% versus 0, diarrhea 6% versus 0, dyspnea 3% versus 9%, and pain 3% versus 6%. Toxic deaths occurred in four patients (6%) in the topotecan arm. All cause mortality within 30 days of random assignment was 13% on BSC and 7% on topotecan. Conclusion: Chemotherapy with oral topotecan is associated with prolongation of survival and quality of life benefit in patients with relapsed SCLC.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 414 citationsread the source →

Tumor Patients´ Perceived Changes of Specific Attitudes, Perceptions, and Behaviors Due to the COVID-19 Pandemic and Its Relation to Reduced Wellbeing.

Background: During the COVID-19 pandemic, the Working Group "Prevention and Integrative Oncology" (PRIO) in the German Cancer Society has initiated flash interviews and surveys. One of these stated increasing rates of fears and mental stress of tumor patients. Now we aimed to analyze whether tumor patients did perceive changes in their attitudes and behaviors related to their relationships, awareness of nature and quietness, interest in spiritual issues, or feelings of worries and isolation. A further point of interest was how these perceived changes could be predicted, either by meaning in life, spirituality as a resource to cope, perceived fears and worries, or particularly by their wellbeing. Materials and methods: Online survey with standardized questionnaires (i.e., WHO-Five Well-being Index (WHO5), Meaning in Life Questionnaire (MLQ), Spiritual and Religious Attitudes to cope with illness (SpREUK-15), Gratitude/Awe scale (GrAw-7)) among 292 tumor patients (72% men; mean age 66.7 ± 10.8 years; 25% < 60 years, 33% 60-70 years, 41% > 70 years) from Germany between May 6 to June 10, 2020. Results: Patients´ wellbeing (WHO5) scores were in the lower range (14.7 ± 6.0); 35% scored < 13, indicating depressive states. Wellbeing was significantly higher in older persons and lower in younger ones (F=11.1, p<.0001). Most were irritated by different statements about the danger and the course of the corona infection in the public media (60%), and 57% were worrying to be infected and to have a complicated course of disease. Because of the restrictions, patients noticed changes in their attitudes and behaviors (measured with the 12-item Perceptions of Change Scale): 1) Perception of nature and silence (Cronbach´s alpha = .82), 2) Worrying reflections and loneliness (Cronbach´s alpha = .80), 3) Interest in spirituality (Cronbach´s alpha = .91), 4) Intense relationships (Cronbach´s alpha = .64). These perceptions of change were similar in women and men, age groups and also with respect to tumor stages. Regression analyses revealed that the factor Perception of nature and silence was predicted best by patients´ ability to value and experience the 'wonder' of the present moment (in terms of wondering awe and gratitude) and by patients´ search for meaning in life. The factor Worrying reflections and loneliness was predicted best by their search for meaning in life and by feelings of being under pressure because of the Corona pandemic. Interest in spirituality was predicted best by search for an access to a spiritual source and by frequency of praying. Intense relationships were explained with weak predictive power by patients´ ability to reflect life concerns. Patients´ wellbeing during the Corona pandemic was predicted (R2 =.57) by a mix of disease and pandemic related stressor, and by available resources (meaning in life and religious trust). Conclusion: In this study among tumor patients from a secular society the topics meaning in life, having (religious) trust, stable relationships, mindful encounter with nature, and times of reflection were found to be of importance. To overcome tumor patients´ feelings of isolation, depressive states, and insecurity about future perspectives, further support is needed, particularly in their socio-spatial surrounding. These are the domains of psychotherapy and spiritual care. The planned integration of structured access to spiritual care seems to be important, not only for the field of cancer care. As the findings refer to patients´ self-perceptions, longitudinal studies are required to substantiate these perceived changes.

Frontiers in psychiatry · 32 citationsread the source →

Silent loss and the clinical encounter: Parents' and physicians' experiences of stillbirth-a qualitative analysis.

Background: In the United States, an estimated 70 stillbirths occur each day, on average 25,000 each year. Research into the prevalence and causes of stillbirth is ongoing, but meanwhile, many parents suffer this devastating loss, largely in silence, due to persistent stigma and taboo; and many health providers report feeling ill equipped to support grieving parents. Interventions to address bereavement after neonatal death are increasingly common in U.S. hospitals, and there is growing data on the nature of parent bereavement after a stillbirth. However, further research is needed to evaluate supportive interventions and to investigate the parent-clinician encounter during hospitalization following a stillbirth. Qualitative inquiry offers opportunities to better understand the lived experience of parents against the backdrop of clinicians' beliefs, intentions, and well-meaning efforts to support grieving parents. Methods: We present a secondary qualitative analysis of transcript data from 3 semi-structured focus groups conducted with parents who had experienced a stillbirth and delivered in a hospital, and 2 focus groups with obstetrician-gynecologists. Participants were drawn from the greater Seattle region in Washington State. We examine parents' and physicians' experiences and beliefs surrounding stillbirth during the clinical encounter using iterative discourse analysis. Results: Women reported that the cheery, bustling environment of the labor and delivery setting was a painful place for parents who had had a stillbirth, and that the well-meaning attempts of physicians to offer comfort often had the opposite effect. Parents also reported that their grief is deeply felt but not socially recognized. While physicians recognized patients' grief, they did not grasp its depth or duration. Physicians viewed stillbirth as an unexpected clinical tragedy, though several considered stillbirth less traumatic than the death of a neonate. In the months and years following a stillbirth, these parents continue to memorialize their children as part of their family. Conclusions: Hospitals need to examine the physical environment for deliveries and, wherever possible, offer designated private areas with staff trained in stillbirth care. Training programs in obstetrics need to better address the bereavement needs of parents following a stillbirth, and research is needed to evaluate effective bereavement interventions, accounting for cultural variation. Critical improvements are also needed for mental health support beyond hospitalization. Finally, medical professionals and parents can play an important role in reversing the stigma that surrounds stillbirth.

BMC pregnancy and childbirth · 100 citationsread the source →

Association of hearing impairment and mortality in older adults.

Background: Hearing impairment (HI) is highly prevalent in older adults and is associated with social isolation, depression, and risk of dementia. Whether HI is associated with broader downstream outcomes is unclear. We undertook this study to determine whether audiometric HI is associated with mortality in older adults. Methods: Prospective observational data from 1,958 adults ≥70 years of age from the Health, Aging, and Body Composition Study were analyzed using Cox proportional hazards regression. Participants were followed for 8 years after audiometric examination. Mortality was adjudicated by obtaining death certificates. Hearing was defined as the pure-tone average of hearing thresholds in decibels re: hearing level (dB HL) at frequencies from 0.5 to 4kHz. HI was defined as pure-tone average >25 dB HL in the better ear. Results: Of the 1,146 participants with HI, 492 (42.9%) died compared with 255 (31.4%) of the 812 with normal hearing (odds ratio = 1.64, 95% CI: 1.36-1.98). After adjustment for demographics and cardiovascular risk factors, HI was associated with a 20% increased mortality risk compared with normal hearing (hazard ratio = 1.20, 95% CI: 1.03-1.41). Confirmatory analyses treating HI as a continuous predictor yielded similar results, demonstrating a nonlinear increase in mortality risk with increasing HI (hazard ratio = 1.14, 95% CI: 1.00-1.29 per 10 dB of threshold elevation up to 35 dB HL). Conclusions: HI in older adults is associated with increased mortality, independent of demographics and cardiovascular risk factors. Further research is necessary to understand the basis of this association and whether these pathways might be amenable to hearing rehabilitation.

The journals of gerontology. Series A, Biological sciences and medical sciences · cohort or longitudinal · 106 citationsread the source →

Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study.

Background: The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI. Methods: CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582). Findings: Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13-15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30-66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE <8) was found in 207 (30%) patients in the ER stratum, 665 (53%) in the admission stratum, and 1547 (84%) in the ICU stratum. Among patients with moderate-to-severe TBI in the ICU stratum, 623 (55%) patients had unfavourable outcome at 6 months (GOSE <5), similar to the proportion predicted by the IMPACT prognostic model (observed to expected ratio 1·06 [95% CI 0·97-1·14]), but mortality was lower than expected (0·70 [0·62-0·76]). Interpretation: Patients with TBI who presented to European centres in the core study were older than were those in previous observational studies and often had comorbidities. Overall, most patients presented with mild TBI. The incomplete recovery of many patients should motivate precision medicine research and the identification of best practices to improve these outcomes. Funding: European Union 7th Framework Programme, the Hannelore Kohl Stiftung, OneMind, and Integra LifeSciences Corporation.

The Lancet. Neurology · cohort or longitudinal · 381 citationsread the source →

The tinnitus functional index: development of a new clinical measure for chronic, intrusive tinnitus.

Objectives: Chronic subjective tinnitus is a prevalent condition that causes significant distress to millions of Americans. Effective tinnitus treatments are urgently needed, but evaluating them is hampered by the lack of standardized measures that are validated for both intake assessment and evaluation of treatment outcomes. This work was designed to develop a new self-report questionnaire, the Tinnitus Functional Index (TFI), that would have documented validity both for scaling the severity and negative impact of tinnitus for use in intake assessment and for measuring treatment-related changes in tinnitus (responsiveness) and that would provide comprehensive coverage of multiple tinnitus severity domains. Design: To use preexisting knowledge concerning tinnitus-related problems, an Item Selection Panel (17 expert judges) surveyed the content (175 items) of nine widely used tinnitus questionnaires. From those items, the Panel identified 13 separate domains of tinnitus distress and selected 70 items most likely to be responsive to treatment effects. Eliminating redundant items while retaining good content validity and adding new items to achieve the recommended minimum of 3 to 4 items per domain yielded 43 items, which were then used for constructing TFI Prototype 1.Prototype 1 was tested at five clinics. The 326 participants included consecutive patients receiving tinnitus treatment who provided informed consent-constituting a convenience sample. Construct validity of Prototype 1 as an outcome measure was evaluated by measuring responsiveness of the overall scale and its individual items at 3 and 6 mo follow-up with 65 and 42 participants, respectively. Using a predetermined list of criteria, the 30 best-functioning items were selected for constructing TFI Prototype 2.Prototype 2 was tested at four clinics with 347 participants, including 155 and 86 who provided 3 and 6 mo follow-up data, respectively. Analyses were the same as for Prototype 1. Results were used to select the 25 best-functioning items for the final TFI. Results: Both prototypes and the final TFI displayed strong measurement properties, with few missing data, high validity for scaling of tinnitus severity, and good reliability. All TFI versions exhibited the same eight factors characterizing tinnitus severity and negative impact. Responsiveness, evaluated by computing effect sizes for responses at follow-up, was satisfactory in all TFI versions. In the final TFI, Cronbach's alpha was 0.97 and test-retest reliability 0.78. Convergent validity (r = 0.86 with Tinnitus Handicap Inventory [THI]; r = 0.75 with Visual Analog Scale [VAS]) and discriminant validity (r = 0.56 with Beck Depression Inventory-Primary Care [BDI-PC]) were good. The final TFI was successful at detecting improvement from the initial clinic visit to 3 mo with moderate to large effect sizes and from initial to 6 mo with large effect sizes. Effect sizes for the TFI were generally larger than those obtained for the VAS and THI. After careful evaluation, a 13-point reduction was considered a preliminary criterion for meaningful reduction in TFI outcome scores. Conclusions: The TFI should be useful in both clinical and research settings because of its responsiveness to treatment-related change, validity for scaling the overall severity of tinnitus, and comprehensive coverage of multiple domains of tinnitus severity.

Ear and hearing · clinical trial · 564 citationsread the source →

Understanding Emotion Regulation Strategies Among Youths: A Qualitative Study

The period of youth encompasses a myriad of experiences that often elicit a range of emotions from the individual. This study was conducted to understand emotion regulation (ER) among youths, specifically to identify strategies employed by youths to regulate emotions, and to understand the perceived importance and impact of ER. Qualitative data were collected through one-to-one semi-structured interviews ( n = 25) and focus group discussions ( n = 11; total 70 participants) among youths aged between 15 and 24 years. Interviews were transcribed verbatim and inductive thematic analysis was used to analyze the data. ER strategies engaged by youths in this study were classified into the following themes: (1) developing emotional awareness and acceptance, (2) emotional catharsis, (3) calling for a timeout, and (4) positive thinking and reframing. Youths perceived the importance of regulating emotions as (1) ER contributes to rational thinking and decision-making, (2) poor ER worsens mental wellbeing, (3) ER provides stability in life, and has (4) relevance to current life stage and environment. Findings from this study illustrate the essential role of ER for youth’s healthy functioning and demonstrate the value of strengthening emotional regulatory capacities in them.

Journal of Adolescent Research · 18 citationsread the source →

A comparison between patients with dysfunctional breathing and patients with asthma.

Introduction: The term dysfunctional breathing (DB) has been introduced to describe patients who display a divergent breathing pattern and have breathing problems that cannot be attributed to a specific medical diagnosis such as asthma, chronic obstructive pulmonary disease or sensory hyper-reactivity. Objective: The objective of this study was to investigate similarities and differences in patients with DB, and patients with well-controlled asthma regarding health-related quality of life, anxiety, depression, sense of coherence (SOC), hyperventilation and effects on daily life. Methods: Twenty-five consecutive patients with DB, and 25 age- and sex-matched patients with asthma (ages 20-73 years) participated in the study. The diagnosis of DB was based on the presence of a dysfunctional breathing pattern and at least five symptoms associated with DB. Results: The group with DB had lower health-related quality of life (short form 36): vitality (mean) 47 vs 62, social functioning 70 vs 94 and role emotional 64 vs 94 (P < 0.05) than the asthmatic group. The DB group also had a higher prevalence of anxiety (56% vs 24%) and a lower SOC (134 vs 156) (P < 0.05). Hyperventilation, defined according to the Nijmegen symptoms questionnaire, was observed in 56% of patients with DB vs 20% in the asthma group (P = 0.02). Conclusions: The results of the study indicate that patients with DB are more disabled than patients with well-controlled asthma. There is a great need for more knowledge about breathing symptoms of a dysfunctional nature, to be able to identify and manage these patients adequately.

The clinical respiratory journal · cohort or longitudinal · 55 citationsread the source →

A review and content analysis of engagement, functionality, aesthetics, information quality, and change techniques in the most popular commercial apps for weight management.

Background: There are thousands of apps promoting dietary improvement, increased physical activity (PA) and weight management. Despite a growing number of reviews in this area, popular apps have not been comprehensively analysed in terms of features related to engagement, functionality, aesthetics, information quality, and content, including the types of change techniques employed. Methods: The databases containing information about all Health and Fitness apps on GP and iTunes (7,954 and 25,491 apps) were downloaded in April 2015. Database filters were applied to select the most popular apps available in both stores. Two researchers screened the descriptions selecting only weight management apps. Features, app quality and content were independently assessed using the Mobile App Rating Scale (MARS) and previously-defined categories of techniques relevant to behaviour change. Inter-coder reliabilities were calculated, and correlations between features explored. Results: Of the 23 popular apps included in the review 16 were free (70%), 15 (65%) addressed weight control, diet and PA combined; 19 (83%) allowed behavioural tracking. On 5-point MARS scales, apps were of average quality (Md = 3.2, IQR = 1.4); "functionality" (Md = 4.0, IQR = 1.1) was the highest and "information quality" (Md = 2.0, IQR = 1.1) was the lowest domain. On average, 10 techniques were identified per app (range: 1-17) and of the 34 categories applied, goal setting and self-monitoring techniques were most frequently identified. App quality was positively correlated with number of techniques included (rho = .58, p < .01) and number of "technical" features (rho = .48, p < .05), which was also associated with the number of techniques included (rho = .61, p < .01). Apps that provided tracking used significantly more techniques than those that did not. Apps with automated tracking scored significantly higher in engagement, aesthetics, and overall MARS scores. Those that used change techniques previously associated with effectiveness (i.e., goal setting, self-monitoring and feedback) also had better "information quality". Conclusions: Popular apps assessed have overall moderate quality and include behavioural tracking features and a range of change techniques associated with behaviour change. These apps may influence behaviour, although more attention to information quality and evidence-based content are warranted to improve their quality.

The international journal of behavioral nutrition and physical activity · review · 228 citationsread the source →

Therapy interventions for children with neurodisabilities: a qualitative scoping study.

Background: Therapy interventions emerged four times in the top 10 research priorities in a James Lind Alliance research prioritisation exercise for children with neurodisabilities (Morris C, Simkiss D, Busk M, Morris M, Allard A, Denness J, et al. Setting research priorities to improve the health of children and young people with neurodisability: a British Academy of Childhood Disability-James Lind Alliance Research Priority Setting Partnership. BMJ Open 2015;5:e006233). The National Institute for Health Research (NIHR) commissioned this study as part of an information-gathering exercise in response to this. Objectives: The objectives were to (1) describe the current practice, approaches and schools of thought in relation to physiotherapy, occupational therapy and speech and language therapy for children with neurodisability; (2) explore clinical decision-making; (3) investigate views on outcomes and their measurement, particularly participation as an outcome, that is, the child's ability to have the opportunity to be involved in life situations and activities (e.g. communication, mobility, interpersonal interactions, self-care, learning and applying knowledge); (4) seek views on the aspects of therapy interventions that have an impact on outcomes; and (5) elicit stakeholder views on research needs and priorities. Design, setting and participants: More than 70 professionals (therapists, service leads, paediatricians and education staff) and 25 parents participated in a qualitative interview (either individually or as part of a focus group). Results: Professional thinking and models of service delivery are in a state of flux and development. There is a move towards goals-focused, family-centred approaches. Work tends to be highly individualised, with few protocols. Parents are certain of the value of therapies, although they may experience difficulties with provision and may seek (additional) private provision. Therapy interventions are conceived as three components: the therapist, the procedures/equipment, etc., and the wider therapeutic environment. They are believed to be highly complex and poorly understood. Although participation is widely endorsed as a core intervention objective of therapy interventions, its suitability, or appropriateness, as an outcome measure was questioned. Other child and/or parent outcomes were identified as more or equally important. Notions of intermediate outcomes - in terms of body structure/function, and the achievement of activities - were regarded as important and not counter to participation-focused approaches. Among therapists, research on intervention effectiveness was (cautiously) welcomed. A number of methodological challenges were identified. A portfolio of study designs - quantitative and qualitative, experimental and observational - was called for, and which included economic evaluation and clear pathways to impact. Limitations: The study was not successful in recruiting children and young people. Further work is required to elucidate the views of this key stakeholder group. Conclusions: Therapy interventions are poorly understood. There was strong support, tempered a little by concerns among some about the feasibility of demonstrating impact, for investment in research. Future work: The identification of research priorities was a core study objective, and a wide-ranging research agenda was identified. It included 'foundational' research into neurodisability, the active components of therapy interventions and the concept of participation. Three areas of evaluation were identified: overall approaches to therapy, service organisation and delivery issues, and the evaluation of specific techniques. Parents regarded evaluations of approaches to therapy (e.g. goals-focused; supporting family-self management) as priorities, along with evaluations of models of service provision. Professionals' views were broadly similar, with an additional emphasis on methodological research. In terms of specific techniques, there was no shared agreement regarding priorities, with views informed by personal interests and experiences. Funding: The NIHR Health Technology Assessment programme.

Health technology assessment (Winchester, England) · 17 citationsread the source →

Shifting gender norms to improve HIV service uptake: Qualitative findings from a large-scale community mobilization intervention in rural South Africa.

Background: Interventions to improve HIV service uptake are increasingly addressing inequitable and restrictive gender norms. Yet comparatively little is known about which gender norms are most salient for HIV testing and treatment and how changing these specific norms translates into HIV service uptake. To explore these questions, we implemented a qualitative study during a community mobilization trial targeting social barriers to HIV service uptake in South Africa. Methods: We conducted 55 in-depth interviews in 2018, during the final months of a three-year intervention in rural Mpumalanga province. Participants included 25 intervention community members (48% women) and 30 intervention staff/community-opinion-leaders (70% women). Data were analyzed using an inductive-deductive approach. Results: We identified three avenues for gender norms change which, when coupled with other strategies, were described to support HIV service uptake: (1) Challenging norms around male toughness/avoidance of help-seeking, combined with information on the health and preventive benefits of early antiretroviral therapy (ART), eased men's fears of a positive diagnosis and facilitated HIV service uptake. (2) Challenging norms about men's expected control over women, combined with communication and conflict resolution skill-building, encouraged couple support around HIV service uptake. (3) Challenging norms around women being solely responsible for the family's health, combined with information about sero-discordance and why both members of the couple should be tested, encouraged men to test for HIV rather than relying on their partner's results. Facility-level barriers such as long wait times continued to prevent some men from accessing care. Conclusions: Despite continued facility-level barriers, we found that promoting critical reflection around several specific gender norms, coupled with information (e.g., benefits of ART) and skill-building (e.g., communication), were perceived to support men's and women's engagement in HIV services. There is a need to identify and tailor programming around specific gender norms that hinder HIV service uptake.

PloS one · 15 citationsread the source →

The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking.

Background: In almost 2 decades of naltrexone research for treating alcoholism, there have been 29 published randomized placebo-controlled trials of opioid antagonists, primarily naltrexone, for the treatment of alcohol dependence. The present review builds on prior systematic reviews while maximizing the number of included studies to date, for the purpose of resolving inconsistencies in naltrexone's reported efficacy across trials. Clinical trial results in this article are evaluated by the type of outcome measure used to determine naltrexone's treatment advantage, that is, measures related to reducing heavy drinking versus those related to increasing abstinence. Methods: We conducted a Medline search to identify double-blind studies from 1990 to the present (2006) that evaluated the use of anopiate antagonist for the treatment of alcohol dependence. There were 29 studies identified, representing 5997 alcohol-dependent patients, which met our study inclusion criteria for this review. Studies were evaluated in this review on 4 prespecified drinking outcomes-2 related to "any drinking" and 2 related to "heavy or excessive drinking." Results: In the treatment of alcohol dependence, we found that 19 (70%) of 27 clinical trials that measured reductions in "heavy or excessive drinking" demonstrated an advantage for prescribing naltrexone over placebo, whereas only 9 (36%) of 25 clinical trials that measured abstinence or "any drinking" found an advantage for medication over placebo. Conclusion: The majority of double-blind clinical trials in the literature favored prescribing naltrexone for alcohol dependence to reduce heavy drinking. This finding is consistent with our understanding of naltrexone's mechanism of action of decreasing excessive drinking by reducing the reward associated with drinking alcohol. Thus, we conclude that outcome measures related to heavy or excessive drinking are most relevant to defining naltrexone's therapeutic effects. Factors influencing naltrexone response (treatment adherence and distinct patient subgroups) are also discussed.

Journal of clinical psychopharmacology · review · 120 citationsread the source →

Fetal Alcohol Syndrome

Objectives After completing this article, readers should be able to:Alcohol is the most common human teratogen, but its significant physical and neurobehavioral effects are completely preventable. Fetal alcohol syndrome (FAS) was described initially in case reports by Lemoine in 1968 and Jones and Smith in 1973. It is a pattern of physical, behavioral, and cognitive abnormalities seen in individuals exposed to alcohol in utero. The association between these findings and maternal use of alcohol during pregnancy has been well documented, with studies in both animals and humans suggesting teratogenicity from as little as one binge drinking episode in early pregnancy. The diagnostic criteria are not a result of fetal physical dependence or addiction or the presence of alcohol in the neonate at delivery; rather, they are teratogenic effects caused by in utero exposure to alcohol in the mother’s blood. In 1996, following a congressional mandate that the Institute of Medicine and National Academy of Sciences study FAS and related birth defects, these institutions published a review of the current understanding of FAS and revised the diagnostic criteria. Despite increased awareness of this preventable birth defect,new cases continue to occur in significant numbers and are routinely under-recognized by medical personnel. It is imperative that maternal alcohol use and its sequelae be considered and addressed in daily pediatric practice. The purpose of this article is to review the diagnosis, epidemiology, management, prognosis, and prevention of FAS.FAS represents a specific pattern of findings associated with in utero exposure to alcohol(Table 1). These include: pre- and postnatal growth deficiency, minor facial anomalies(short palpebral fissures, ptosis, flat midface with upturned nose, smooth philtrum, thin upper lip), and central nervous system (CNS) neurodevelopmental findings(microcephaly, agenesis of the corpus callosum, tremors, hyperactivity, learning disabilities, cognitive impairments). Infants exposed to alcohol in utero also can have major malformations, including cardiac defects, cleft lip, cleft palate, and limb reduction deformities. Using the criteria established by the Institute of Medicine, the diagnosis of FAS requires a history of maternal alcohol use during the pregnancy (proven or presumed) and elements of the three primary diagnostic categories (Table 2). If maternal alcohol use is not confirmed, the diagnosis of FAS may still be used, but the missing history of in utero alcohol exposure should be noted. Fetal alcohol effects are minor findings that are not necessarily unique to alcohol,but that are proven to occur in association with in utero alcohol exposure. However, this term is imprecise. The Institute of Medicine uses the terms partial FAS with confirmed maternal alcohol exposure, alcohol-related birth defects (ARBD), and alcohol-related neurodevelopmental disorder (ARND) to describe alcohol-related effects not meeting the criteria for FAS.The incidence of FAS, ARBD, and ARND has been difficult to characterize because of significant variations in study populations and methods of data collection. Prospective studies and newborn discharge diagnosis data give lower incidence rates; retrospective studies and clinic-based studies tend to report higher incidence rates. The reported ranges of FAS, ARBD, and ARND are generally between 0.5 and 5 per 1,000 children, making alcohol exposure the most common cause of birth defects. Significant controversy surrounds the amount of alcohol ingestion that presents a risk to the fetus and whether a single exposure is of greater consequence than a pattern of exposure during fetal development. Initial studies of human alcohol teratogenicity examined the average amount of alcohol consumed per day during pregnancy. These studies did not demonstrate a difference between infants exposed to higher levels of alcohol or to binge drinking. However, the definitions of binge drinking were vague,and neurobehavioral and longitudinal effects were not addressed. This approach also failed to distinguish between infrequent binge drinkers who may have occasional high blood alcohol levels and mild-to-moderate regular drinkers who have lower peak blood alcohol levels but a more continuous fetal exposure. Subsequent animal studies have helped define the specific gestational timing and doses of alcohol needed to produce both structural and behavioral teratogenic effects. Specifically, animal studies suggest that: 1)third trimester alcohol exposure decreases brain weight and numbers of neurons, 2) peak blood alcohol concentration (affected by both dose and rate of consumption) is more critical than the same total dose with lower peak blood alcohol concentration, and 3)exposure early in the pregnancy can produce more severe and more consistent effects. An absolute threshold and critical time period for exposure is suspected, but has yet to be demonstrated. If this information is extrapolated to human alcohol teratogenicity, one can predict potential fetal effects from a single binge episode (five or more drinks in one sitting) during early development. However, the effects of low total alcohol consumption in a pattern that avoids high peak blood alcohol concentrations (ie, one to two drinks per week with no binge episodes) are unknown at this time. The prevalence of maternal alcohol consumption during pregnancy increased from 12.4% to 16.3% between 1991 and 1995. Frequent drinking during pregnancy, defined as more than seven drinks per week, increased from 0.8% to 3.5%. In the face of increasing maternal alcohol consumption,researchers still cannot define the threshold for alcohol toxicity in the fetus. Developing organisms are uniquely susceptible to external teratogenic influences. The clinical findings in FAS result from exposure of the developing fetus to toxic levels of alcohol and its metabolites at critical periods in development. The specific pathophysiology remains unknown, but may involve free radical formation that causes cellular damage in the developing tissues of the fetus. Exposure in the first trimester affects organogenesis and craniofacial development, leading to minor and major malformations, such as the characteristic facial features and ARBD (Table 1). Excessive cell death in the midline of the developing embryo may account for the development of these facial features. Continuing alcohol use by the mother in later pregnancy causes decreased fetal growth that results in low birthweight and affects postnatal growth. Alcohol use most likely affects CNS development throughout the pregnancy, as the brain is forming early in the first trimester and is undergoing a growth spurt with maturation of the neurons in the second and third trimesters. Thus,alcohol exposure at varying times in pregnancy can cause similar CNS neurodevelopmental effects. Alcohol use also affects fetal nutrition. Obviously,alcoholism may affect maternal dietary habits and health maintenance behaviors. In addition, alcohol affects the maternal metabolism of essential nutrients by decreasing intestinal absorption, increasing renal and hepatic metabolism, and decreasing placental uptake and availability to the fetus. Finally, the use of other drugs (marijuana, nicotine,caffeine) that commonly accompanies alcohol consumption can have detrimental effects on the fetus. Clear delineation of alcohol-related effects is difficult in many situations where polysubstance use is present. Differences in the severity and spectrum of FAS have been observed based on genetic background, but it is unclear whether confounding variables may have affected the data. For example, population-based studies document up to 10-fold higher prevalence rates of FAS among Native American tribes than in the overall American population. However, individual tribes have markedly differing prevalence rates of FAS. This may be due to confounding factors in the population-based approach, such as counting each sibling of an affected family as a separate case. If a family that included six affected children was counted as six individual cases, the local prevalence of FAS would be higher than if the same family was counted as a single case (one mother delivering multiple children who had FAS). The two methods of interpreting the data would result in different conclusions about the prevalence of FAS within a small, closely related community, resulting in different genetic implications. One of the issues under investigation is the possible genetic susceptibility within the Native American population to the teratogenic affects of alcohol. Further work is necessary to establish the cause of the varying prevalence rates. The concordance of FAS is higher in monozygotic twins than in dizygotic twins, supporting the concept of genetic factors in the fetal effects of alcohol. Mouse embryo studies show variation in CNS injury when the same dose of alcohol is given to different strains of mice,further demonstrating the variation in phenotype based on genetic background. One possible mechanism of heritable susceptibility to FAS may be genetically encoded differences in alcohol dehydrogenase, the enzyme responsible for metabolizing alcohol in the liver. In mothers of children who have FAS, the enzyme may be less functional, resulting in higher peak blood alcohol concentrations after the ingestion of alcohol. Alternatively, the fetus may be deficient in alcohol dehydrogenase activity and, thus,less able to tolerate elevated maternal alcohol levels. Clearly, the effect of genetic variation on susceptibility to in utero alcohol toxicity is an area for future research. Alcohol exposure can continue postnatally if the infant is breastfeeding. Alcohol is excreted in human milk at concentrations similar to blood levels, but acetaldehyde,an alcohol metabolite that may act as a teratogen, is not excreted into human milk. Although the resulting serum alcohol level in the infant may be low, the combined effect of alcohol on the physiologic and social aspects of the breastfeeding relationship are significant. Three points are of particular concern. First, infants’nursing behavior and total consumption of milk are adversely affected by maternal alcohol use immediately prior to a feeding. Second, suckling-induced prolactin and oxytocin release are inhibited by alcohol. Third,infants born to alcohol-abusing mothers have poor suck patterns and do not feed well at the breast. These findings are of significance to the nutritional and emotional aspects of the mother-infant relationship.FAS is a clinical diagnosis assigned in the setting of maternal alcohol use. The typical pattern of associated features should trigger an investigation into possible fetal alcohol exposure and evaluation for other aspects of the syndrome. In many situations, the diagnosis will not be clear, requiring further evaluation by clinical geneticists and neurodevelopmental specialists, with chromosomal analysis for other causes of facial dysmorphology and neurodevelopmental abnormalities. Neonatal diagnosis usually depends on characteristic facial features, suspected in utero alcohol exposure, low birthweight, poor growth, and microcephaly (Tables 1 and 3). The combination of congenital malformations and poor growth should prompt an investigation into prenatal alcohol exposure. The neonate who has FAS may manifest CNS signs, such as irritability and hypersensitivity,hypotonia, poor feeding, and difficulty bonding with caregivers. Congenital malformations and CNS signs are nonspecific, however; facial features are the most useful criteria in the newborn and infant. The diagnosis of FAS is easier between ages 2 and 11 years, when the facial features are still prominent and typical CNS dysfunction emerges clinically. As the child approaches school age, the behavioral and cognitive aspects of the syndrome may become more pronounced, often causing difficulty with developmental tasks. From school entry through adolescence, these aspects can affect school performance and social interactions with peers. Cognitive manifestations, such as memory deficits and slow information processing, are reflected in intelligence quotient (IQ) testing. Typical FAS neurobehavioral and adaptive manifestations in the school-age child include attention deficit disorder (which may be unresponsive to stimulant medication),impulsiveness, extreme mood changes, anxiety, aggressive behavior, resistance to change, frequent temper tantrums,and difficulties with social peer interactions. In addition, these children may have speech impairment as a result of anatomic differences of the jaw, fine motor dysfunction of the oropharyngeal muscles, or hearing deficits. Cognitive and behavioral difficulties also affect communication skills. A recent study estimated that the social abilities of a child who has FAS plateau at the 6-year-old level and may not progress beyond this point (see Thomas et al in Suggested Reading). The authors also showed that the interpersonal relationship skills of children who had FAS were below the level of verbal IQ-matched controls. It is easy to see how these issues will affect social interactions and classroom skills negatively. Diagnosis in the school-age child can be made clinically if the facial features are classic, CNS abnormalities are present, and maternal alcohol use during pregnancy is established. Chromosomal analysis,genetic evaluation, and neurodevelopmental evaluation are important in confirming the diagnosis. As a child ages, the facial features (especially the smooth philtrum, thin upper lip, and flat midface) may become harder to distinguish, making clinical diagnosis more difficult (Figs. 1 and 2). “Catch-up” growth may occur in adolescence, particularly in females. The CNS manifestations of the syndrome and the resulting impact on cognitive skills become more prominent in adolescence. Problem-solving abilities, abstract reasoning, and time and money management skills are deficient. These teenagers can be impulsive, use poor judgment, and fail to understand the consequences of their actions. In adulthood, these individuals can be isolated and withdrawn, with poor adaptive living skills. Some are unable to work or manage money and often require structured living arrangements. Cognitive abilities vary considerably within the group of children affected with FAS. Some can function successfully in a regular classroom and attain meaningful employment and even college. More severely affected children may have significant developmental delay and learning disabilities that require special programming at school and lifelong supportive services. IQ scores of children who have FAS range from 16 to 105, with an average of 66. In comparison, IQ scores of male patients who have fragile X syndrome range from 30 to 55, and those of children who have Down syndrome range from 25 to 50, with only a few testing in the 60s. FAS is among the most common causes of mental retardation, but as demonstrated by the average score, most children have only mild retardation (IQ scores below 70 are consistent with mental retardation). Even children who have FAS and normal IQ scores may have significant neurobehavioral deficits and adaptive problems that affect their independence, and they are at higher risk for severe behavioral problems and psychiatric disorders. Approximately 62% of patients who have FAS have severe behavioral problems compared with 15% to 32% of those who have Down syndrome. Individuals who have FAS may face more difficulties holding a job, maintaining social relationships, and living independently than people who have Down syndrome and similar or even lower IQs.For example, consider John, a 7-year-old boy who was exposed to alcohol in utero and has facial features consistent with FAS, height at the 10th percentile,weight less than the 5th percentile, and head circumference less than the 5th percentile for age. FAS was diagnosed clinically in his first year of life based on the in utero alcohol exposure, growth retardation,microcephaly, and facial features in conjunction with a negative evaluation for genetic and other known disorders. His home environment was evaluated, support services were arranged for his mother, and evaluation for alcohol-related disability was arranged for his older sister. John’s IQ is 75. Speech delay affects his school performance and social interactions. He is having increasing difficulties with attention during the school day, aggressiveness toward peers, mood swings, and temper tantrums. These further impair his school performance and peer interactions. John also has specific difficulties with math and organizational skills. He will require evaluation for supportive behavioral and educational services, despite his normal IQ, and for hearing impairment and will need close monitoring for other problems that may develop in the future. Other social and pathologic processes affect children who are exposed to alcohol in utero. Labeling affected children as having ARND may overlook additional negative influences on their cognition and behavior. For example,many children who have FAS and ARND also live with poverty, unstable home situations, lack of emotional support systems, and inappropriate educational resources. These situations can cause fear, depression, and frustration that may be misinterpreted as alcohol-related behavioral problems. It can be easy to blame all of a child’s difficulties on prenatal alcohol exposure,when part of the problem may be ongoing exposure to external influences. The differential diagnosis of FAS is important because the FAS phenotype is variable and may be difficult to distinguish from other conditions. The physical features can be confused with those of Aarskog syndrome, Williams syndrome, Noonan syndrome, Dubowitz syndrome, Bloom syndrome, fetal hydantoin syndrome, and maternal phenylketonuria fetal effects (Table 4). The neurobehavioral features may be similar to those seen in fragile X syndrome, the 22q11 deletion syndromes, Turner syndrome, or Opitz syndrome (Table 5). When contemplating the diagnosis of FAS, it is important to consider these and other genetic, metabolic,toxicologic, and neurodevelopmental syndromes and to seek consultation as necessary. The early diagnosis of FAS benefits infants and children. Medical intervention, including evaluation of growth and nutrition, management of medical issues related to birth defects, and identification of other medical issues specific to the child in question, is crucial to the care of the child who has FAS. Other appropriate interventions, in the form of educational evaluation and support and community resources, can be accessed and put into place early, allowing the child to reach his or her maximum potential. Developmental delay,functional abilities, speech abilities, and social/behavioral interactions may improve with timely of it is yet to be demonstrated that IQ can with appropriate in FAS). diagnosis may result in of the maternal problem and to community for many of these children live in resulting from alcohol use by the additional support of the family may improve the social the abilities of the addition, other may be diagnosed with or The child in a family may be the most severely affected a result of maternal addiction and maternal and, the most Diagnosis and appropriate may be in affected older the child has been It important to all of a child who has FAS.The National on Fetal Alcohol is a group that educational and supportive for affected by FAS and is in medical and the about the effects of alcohol during pregnancy. has information on support and about FAS that may be useful to and medical also can be at has a in the care of the child who has FAS. the diagnosis is and possible the child should be in early This requires a high of and a who is to the with the family in a but supportive The also consider FAS during evaluation of the older child or who behavioral poor school and Although the differential diagnosis for these findings is it is important to the family and social history that may suggest FAS, ARBD, or If a diagnosis is not clear, the should appropriate for further genetic and neurodevelopmental The to be with the social and educational in the community that can support need to to such resources, development of the potential of the affected and ongoing medical is preventable. The of this in to the medical resources, and human potential is Although diagnosis and to the appropriate is more can be In the American Academy of published for within the community and setting alcohol use in The by because is no established level of alcohol consumption during pregnancy. In addition, the of about the effects of alcohol on the fetus and to of the effects of prenatal alcohol in prominent as in for alcohol and at The is an part of this community to FAS.

Pediatrics in Review · review · 57 citationsread the source →

Developmental Coordination Disorder

For the last 100 years, poor motor coordination in children has been recognized as a developmental problem.1 As early as 1937, these children were classified as “clumsy.”1 Since then, other terms such as “motorically awkward,” “motor impaired,” and “physically awkward” have been used to describe these children, and the terms “developmental apraxia” and “perceptual motor difficulties” have been used to characterize this developmental problem.2,3 Since the 1994 International Consensus Conference on Children and Clumsiness, the term “developmental coordination disorder” (DCD) has been used to describe the condition of children with motor incoordination.1,4 The purpose of this article is to provide the following information about DCD: (1) definition, (2) prevalence, (3) etiology, (4) discussion regarding the difficulties in classifying these children, (5) common characteristics, (6) long-term prognosis, and (7) brief review of treatment approaches. Developmental coordination disorder, a chronic and usually permanent condition found in children, is characterized by motor impairment that interferes with the child's activities of daily living and academic achievement.3,5 In order for a child to be diagnosed with DCD, these motor impairments must negatively affect some other aspect of his or her life.6 Impairment alone, however, does not qualify a child for the diagnosis of DCD; the motor impairment must not be caused by or have the symptoms of an identifiable neurological problem.2,5 That is, the child must not have any disturbances of muscle tone (ataxia or spasticity), sensory loss, or involuntary movements. If mental retardation is present, the testable IQ of the child must be greater than 70 and the motor impairments must be greater than what would normally be expected for children with mental retardation.5 Finally, a child diagnosed with DCD must not meet the criteria for a diagnosis of pervasive developmental disorder.6 Developmental coordination disorder appears to be a fairly common disorder of childhood and is usually identified in children between 6 and 12 years of age. Ten years ago, researchers7,8 estimated that DCD occurred in 10% to 19% of school-aged children. With a more precise definition of DCD, the current prevalence is estimated to be between 5% and 8% of all school-aged children,5,9–11 with more boys than girls (2:1) being diagnosed with DCD.12 This difference may reflect higher referral rates for boys, because the behavior of boys with motor incoordination may be more difficult to manage at home and in the classroom.8 In addition, a higher incidence of DCD may be found among children with a history of prenatal or perinatal difficulties.3 Due to the heterogeneity of DCD, finding its cause has been difficult.3 Several theories speculate that the etiology of DCD is part of the continuum of cerebral palsy5,13; is secondary to prenatal, perinatal, or neonatal insult3; or is secondary to neuronal damage at the cellular level in the neurotransmitter or receptor systems.14 Hadders-Algra14 based her view that DCD is a result of damage at the cellular level on evidence that cerebral palsy is often caused by prenatal damage that cannot be identified by current diagnostic techniques. Developmental coordination disorder, a chronic and usually permanent condition found in children, is characterized by motor impairment that interferes with the child’s activities of daily living. Although both standard and nonstandard functional tests are available to identify the specific disabilities experienced by a child with DCD, relating the observed disabilities to the primary impairment(s) or any possible neuropathology is not easily accomplished. The problems experienced by children with DCD are believed to emanate from abnormalities in neurotransmitter or receptor systems rather than from damage to specific groups of neurons or brain regions.15 Children's difficulties with coordination can result from a combination of one or more impairments in proprioception, motor programming, timing, or sequencing of muscle activity. A number of theories have evolved in an attempt to shed light on the specific neuronal processing deficits that contribute to DCD. Current models used to explain the neural regulation of posture and movement during development can serve as a basis for the examination and management of individuals with DCD. Using these models, many of the deficits of motor control observed in these children can be described. A variety of theoretical models exist to explain the role of the nervous system in motor development. Forty years ago, the primitive reflex model was a generally accepted theory used to explain how the brain regulates early motor behavior.16 As development proceeded, the higher centers exerted increasing control over the lower reflexes.16 These earlier models were based on a hierarchy of motor control in which higher centers were capable of planning and executing a motor plan without external or internal feedback from lower centers of the central nervous system (CNS). The more recently proposed systems model suggests a more complex interaction among various levels of the CNS. In the systems model, sensory feedback is interpreted by the CNS, and the appropriate movement strategy is selected based on current experience, the state of the internal and external environment, and memory of similar movements. Edelman's neuronal group selection theory includes aspects of both of these models and proposes that functional groups of neurons exist at all levels of the CNS.17 These neuronal groups are determined by evolution, but their functional integrity is dependent on afferent information produced by movement and experience.17 In this regard, these genetically determined collections of interconnected neurons (neuronal groups) in both cortical and subcortical structures serve as an early repertoire for motor behavior or receipt of specific sensory information.14,17,18 According to neuronal group selection theory, motor development proceeds in 2 phases.15 The first, the phase of primary variability, is characterized by crude and erratic motor activity that does not require sensory information for its initiation or guidance. These self-generated movements give rise to afferent (visual, kinesthetic) inputs that reinforce more specific synaptic connections within each group. An intermediate period in which effective patterns are selected is followed by the secondary variability phase. In this phase, sensory and motor factors interact to establish the intercellular connections that produce the specific and complex muscle contraction patterns that characterize coordinated, goal-directed movement. Reciprocal connections between groups subserving movements in various body parts and representing different parts of visual space are reinforced with each repetition of a particular function. As the more efficient movement patterns are practiced, the appropriate synaptic circuits are reinforced and subsequently established.14,17,19,20 The literature includes a wide variation in terminology and criteria to describe DCD. This variation has made studying the causes of DCD and developing treatment approaches for the child with DCD difficult. In their analysis of clinical trial data, Macnab et al21 identified 5 different subtype profiles of DCD. The first subtype included children with better gross motor than fine motor skills, although both were still below normal while standing balance and visual-perceptual skills were both within normal ranges. Compared with children of the same age with DCD, children in the second subtype scored high on measures of upper-limb speed and dexterity, visuomotor integration, and visual-perception skills, but they demonstrated poor performance on measures of kinesthetic ability (accuracy in discriminating movement and position of the upper limbs) and balance. Children in subtype 3 demonstrated the greatest overall motor involvement and were the only subtype to have difficulty with both kinesthetic and visual skills. Compared with their peers with DCD, children in subtype 4 performed well on kinesthetic tasks but demonstrated poor performance on tasks requiring visual and dexterity skills. Children in subtype 5 demonstrated poor performance on measurements of running speed and agility compared with their peers with DCD; however, they performed well relative to their peers with DCD in the tasks involving visual-perception skills. The development of different classification systems for DCD may have been influenced by the design of motor tests.21 For example, items testing one motor skill may be influenced by a related motor skill (eg, ball-throwing skills cannot be separated from visuomotor skills). In addition, a test may have an over-representation of one skill that could unduly influence the child's performance on the test. For example, having a greater number of items testing gross motor rather than fine motor skills could either positively or negatively influence a child's score, depending on the child's specific strengths and weaknesses. Another difficulty in interpreting the literature on DCD is the lack of inclusion criteria. Geuze et al22 reviewed 164 publications on the study of DCD and found that only 60% of the studies had objective inclusion criteria. Because of this lack of inclusion criteria, Geuze et al recommended that a child scoring below the 15th percentile on standardized tests of motor skills and having an IQ score above 69 would qualify for a diagnosis of DCD. The inconsistency among standardized motor tests used to identify children with DCD is another problem. In one study,5 the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP) and the Movement Assessment Battery for Children (M-ABC) were administered to 157 children with DCD and 155 children with no motor difficulties; the test results were in agreement 82% (kappa=.62) of the time in distinguishing children who had DCD from children who did not have DCD. This is considered a substantial level of agreement.23 In a study of 202 children (101 with DCD and 101 without DCD), the BOTMP and M-ABC agreed only 67% of the time (kappa=.41), which was considered a moderate level of agreement.24 Because the BOTMP and the M-ABC are 2 of the most commonly used tests for identifying children with DCD, the potential lack of agreement by these tests in identifying children who have DCD is a concern. Two primary factors may explain the difference in outcomes between the BOTMP and M-ABC when used to identify children with DCD.24 First, the BOTMP allows the tester to verbally prompt and correct the child during the testing procedure, allowing the child who is dependent on more external controls to do better on the BOTMP. The BOTMP tends to under-identify children with DCD. Second, the M-ABC requires more careful instruction on the part of the examiner and allows more opportunities for the examinee to practice, but does not allow any verbal or physical prompting by the examiner. Children with attention problems may have more difficulty with the careful instructions for the M-ABC. Another difficulty in classifying children with DCD is the overlap with other disorders. Approximately 41% of children with attention-deficit/hyperactivity disorder (ADHD) and 56% of children with learning disabilities also have DCD.5,21 Further confusing the classification scheme is that the terms “developmental coordination disorder,” for which no identifiable organic brain damage is present, and “apraxia,” which is caused by identifiable brain damage, have been used interchangeably.3 Children with DCD may have a wide range of dysfunctions. These dysfunctions can be grouped into 3 areas: gross motor, fine motor, and psychosocial. Many children with DCD have neurological soft signs such as hypotonia, persistence of primitive reflexes, and immature balance reactions that interfere with gross motor development.5,25 These children also may demonstrate an awkward running pattern, fall frequently, drop items, and have difficulty imitating body positions and following 2- to 3-step motor commands.8 Because of their gross motor problems, children with DCD also perform poorly in sporting events,2 possibly due, in part, to their slow reaction and movement times.7 Their decreased participation in sports may result in decreased muscle force.8 Difficulty with handwriting or drawing often is the first identifiable sign of a fine motor problem and is the most frequently mentioned motor problem experienced by children with DCD. Children with DCD frequently have difficulty planning and executing other fine motor skills such as gripping and dressing.26–29 Unfortunately, children with DCD may experience problems not limited to fine or gross motor areas. These children also may experience psychosocial problems at school. Children with DCD may have learning disabilities or reading problems and may be at increased risk for lower intelligence.5,8 They may act out in class more than other children,13 may be the class clown, and may exhibit less socially desirable means of gaining recognition and friends.8 Adolescents with DCD have been found to have fewer friends, and they have more feelings of low self-worth and more anxiety than peers without DCD and younger children with DCD.30 Historically, parents have been told not to worry about their child's clumsiness because the child will outgrow the problem.31 However, current researchers in the area of DCD report that the children do not outgrow clumsiness and that, without intervention, they will not improve.1,8,12,27,31 Losse et al31 tested 17 children aged 6 years and retested them at age 16 years. The children with motor difficulties at 6 years of age continued to exhibit problems at 16 years of age. In another study,32 818 children with DCD were tested for reading comprehension at age 7 years and then again at age 10 years. A positive correlation in poor reading comprehension existed for children with DCD at 7 and 10 years of age. A follow-up study was conducted on 22-year-old individuals (N=55) who at age 7 years had either DCD or attention-deficit/hyperactivity disorder (ADHD), or both.33 The children with DCD and those with both DCD and ADHD had poorer outcomes than their similarly aged peers without DCD and children with ADHD only. The children with DCD and those with both DCD and ADHD were found to have had more criminal offenses, more incidences of substance abuse and other psychiatric disorders, and lower levels of schooling. Treatment approaches used by occupational therapists and physical therapists can be broadly categorized into either bottom-up or top-down approaches (Tab. 1).10,12,34–36 Bottom-up approaches are based on hierarchical theories of motor control. These theories tend to explain the remediation of motor dysfunction through activation of higher levels of neuronal functioning in a child. The bottom-up approaches frequently used in managing children with DCD are sensory integration, the process-oriented treatment approach, and perceptual motor training.34 Summary of Bottom-Up Versus Top-Down Approaches Summary of Bottom-Up Versus Top-Down Approaches In sensory integration therapy, the child is provided sensory stimulation designed to promote motor development and higher cortical learning. A child undergoing sensory integration therapy may show some gains in motor development, but these gains often do not generalize to functional skills.34 Kinesthesia (the perception of one's own body parts, weight, and movement) is integral to the acquisition of motor skills in process-oriented treatment approaches. Therapeutic intervention with process-oriented treatment is based on specifically designed kinesthetic training activities. As described by Laszlo and Bairstow,37 this approach has an inherent reward system built into it through its use of positive reinforcement, presentation of desirable activities within the capabilities of the child, and judicious progression of the level of difficulty. The usefulness of the process-oriented treatment approach has been the subject of considerable study.9,10,37,38 Sims and colleagues35 suggested that much of the success of this approach can be attributed to a strong motivation effect, fostered by positive feedback and a sense of self-competence. Perceptual motor training, an eclectic approach, offers the child with DCD a wide range of motor experiences along with ample opportunities to practice these skills. Often, in outcome studies, children who receive perceptual motor training are compared with children who receive either sensory integration therapy or process-oriented treatment. Children perceptual motor training have been found to demonstrate motor to or greater than those of children either sensory integration therapy or process-oriented perceptual motor training, process-oriented may promote learning through positive feedback and reinforcement, these do not and to the that top-down approaches approaches use a approach to motor skill development and have been influenced by the systems approach to motor learning and control. This approach suggests that motor skills from an interaction of many both internal and external to the approaches also the in which motor behavior intervention and approaches or are the 2 most commonly intervention on of a The theoretical for intervention in a child's motor performance is the result of learning on a specific Motor tasks are into with each and then to the Children with this approach have demonstrated gains in motor skills.34 approaches to motor development problem The approach strategy the to to the and perform the well did plan The child verbal to the to motor learning. In this approach, the as a by the child out how to his or her motor performance on various motor intervention, the results of studies of approaches are In one 10 children with DCD who were with a approach to motor development were compared with 10 children who were with a bottom-up The children were for and groups on various standardized motor tests 10 treatment However, children in the approach group motor skill and to better than children who were the bottom-up and the approach both provide repetition and practice of specific motor skills, and the approach has the of problem The greater success of top-down when compared with bottom-up be a result of the top-down inclusion of both and motor learning with for attention to and memory as the child in activities. The results of these studies, in to outcome measures of the different approaches in children with DCD, would that approaches that systems theory on sensory information being only part of the and motor learning theory be most effective for these 2 a brief of clinical the of various treatment approaches used with children with of Treatment Approaches for Children With Developmental approach to daily occupational performance treatment approach treatment group integration, perceptual motor, gross and fine motor integration Assessment Battery for Test of Motor Test of for of Motor and of of Treatment Approaches for Children With Developmental approach to daily occupational performance treatment approach treatment group integration, perceptual motor, gross and fine motor integration Assessment Battery for Test of Motor Test of for of Motor and of The neuronal group selection theory can provide a for interpreting the in outcomes among the various approaches. children with moderate to cerebral palsy have a limited repertoire of primary neuronal which children with DCD are believed to experience difficulty at the level of secondary variability, that is, in and the most efficient and effective for a normal development, experience a primary role in the neuronal group selection that the for and According to the neuronal group selection theory, this of motor skill during the of secondary variability as a result of of neuronal selection of specific neurons within each repetition of synaptic within and among neuronal and sensory synaptic which act in and cortical and subcortical and following to a variety of motor of these connections is dependent on sensory Bottom-up approaches such as sensory integration, process-oriented and perceptual motor training sensory experience, with less on processing and motor Although an intervention based on information processing may provide the experience to the most effective neuronal bottom-up approaches may not provide for motor practice of and goal-directed tasks in order to reinforce and establish these approaches less on the specific impairments to decreased coordination and more on the of that is, the among a number of structures and systems and the within which the is Treatment based on a top-down approach that provide the child the to in problem while afferent subcortical structures the feedback and to identify and the most efficient movement for the Because integration, internal of motor and appropriate motor at the level of secondary the on sensory rather than factors by the bottom-up approaches in part, be for the observed in outcomes following treatment. A number of motor learning theories have been proposed in an attempt to explain the through which are into more complex According to the motor control and learning theory proposed by and motor circuits that the and following long-term these and functioning neuronal circuits through practice, the child is to motor into more complex movements. and proposed 2 to such the first of which on sensory to neuronal is during the second that the to the specific motor tasks through the and involving the and in the first of learning requires attention and The motor then in the of learning through repetition and top-down approaches meet both of these bottom-up approaches information processing only. the and of the neural in children with DCD is a not Motor control are complex and on functioning of and motor only are children with DCD a group in terms of functional disabilities the specific of the problems observed can from one child to the Because of these an approach to the management of children with DCD is Developmental coordination disorder is a complex disorder 5% to of school-aged children. intervention, these children will to exhibit poor motor skills and show deficits in other as for may (1) the most appropriate level of intervention (2) which produce results that generalize to the and provide long-term in motor (3) what have on the child's motor and (4) motor skills to the that to the

Physical Therapy · review · 472 citationsread the source →

The Pediatric Role in the Care of Children in Foster and Kinship Care

In September 2010, 408,425 children and adolescents resided in foster care. Recent legislation highlights an increasing focus on involving pediatricians in supporting children in foster care and defines specific requirements relevant to the role of pediatricians. After completing this article, readers should be able to: Foster care is intended to provide a temporary haven for children during a time of family crisis when children are at imminent risk for harm. The goals of foster care are to promote child health, safety, permanency, and well-being. Foster care also has the mission of building on family strengths and providing birth parents with the services they need to reconnect (reunify) with their children. Because children fare best in stable and nurturing families, there has been an increased emphasis in the past decade on shortening the time to permanency through reunification, placement with relatives, and adoption. Foster care also has the obligation to prepare youth for independent living when none of these permanency options is possible. In some states, more than one third of children in foster care are in court-ordered (formal) kinship placements, arrangements in which the related (kin) caregiver may or may not be a certified foster parent. Even outside the child welfare system, somewhere between 4% and 8% of children reside with members of their extended family, neighbors, or friends for a variety of reasons. During the past decade, several studies were published reporting that children experience greater placement stability in kinship care than in nonrelative foster care, and that kin caregivers report fewer child behavior problems. Other data indicate that children in kinship care have as many issues as children in foster care, and that kinship caregivers are older, are less healthy, and have less access to services than nonrelative foster parents. However, recognizing that maintaining a child’s ties to his or her family of origin holds advantages for the child, relatively more children are being placed in kinship care as a result of child protective investigation. Other children are spending brief amounts of time in foster care while child welfare attempts to identify and investigate kinship resources. The definition of kin has expanded to include nonrelatives, such as family friends, acquaintances, and neighbors. There is little information about the outcomes of reunification with parents or kinship care, including child health and mental health outcomes and the percentage of kinship homes that undergo disruption. The vast majority of kinship placements are without oversight or subsidy, although recent federal legislation was intended to improve financial support for this group of caregivers. Children in foster care are classified as children who have special health-care needs by the American Academy of Pediatrics (AAP) because of their high prevalence of medical, emotional, behavioral, developmental, educational, and dental health-care problems. Most pediatric practitioners will encounter children and adolescents in foster or kinship care in their practices. It is important that pediatricians be familiar with the effects of childhood trauma and adversity, separation from family, and ongoing uncertainty on child behavior, mental health, and development. Pediatricians are in a unique position to identify problems, make appropriate referrals, and offer support and advice to caregivers. Foster care ideally should be developmentally appropriate and child-centered, and pediatricians can play a crucial role in offering developmentally sound advice and emotional support to caregivers about parenting traumatized children and children who have significant behavior problems. Pediatricians also should suggest ways to promote placement stability and successful permanency. Most maltreated children are not removed from their birth parents, but they appear to have the same health issues as children in foster and kinship care. The knowledge and skills that pediatricians bring to the care of children in foster and kinship care also apply to the larger population of children whose families are involved with child welfare agencies. Of 3.3 million child abuse and neglect reports in 2010, 436,321 (22%) were substantiated, and 254,000 children were removed to foster care. Over the past decade, the increasing trend toward keeping children with their birth parents or with kin caregivers after child protective investigation has reduced the total number of children in foster care. In the United States, on September 30, 2010, 408,425 children and adolescents resided in foster care, 26% in a relative (kinship) foster home, 48% in a nonrelative foster home, and 9% in either a group home or residential care setting. Of the remainder, 4% lived with a preadoptive family, 5% were on a trial discharge with their parents, and 2% were listed as “run-away.”Estimates suggest that more than 700,000 individual children have spent some time in foster care during the preceding 12 months. Census data indicate that approximately four to eight times as many children and teenagers live in informal, unregulated kinship care without child welfare involvement. Approximately 40% of those in foster care are teenagers, whereas 30% are children under age 5 years. Children in foster care range in age from birth to 21 years, although 47 states still emancipate adolescents at age 18 years. Minorities are represented prominently in foster care. In 2010, 29% of children were of African American heritage, 21% Hispanic, 41% white, and 5% of two or more races. Significant concern exists that the overrepresentation of minority children reflects bias in child protective referrals, investigation, and removal, as well as a lower likelihood of reunification after removal. Discrete subpopulations in foster care that present with unique health needs include children who have multiple handicaps, teenagers involved with juvenile justice, pregnant and parenting teenagers, and unaccompanied refugee minors from countries ravaged by war or severe internal strife. The average length of stay in foster care in 2010 was 25 months, with a median of 14.5 months. The lower median is attributed to more intensive permanency planning, resulting in shorter times to reunification or placement with extended family. However, the higher mean is affected by the 25% of children who remain in care for years. Length of stay is affected by several factors: the biological family’s cooperation with the individualized case plan for their family; the availability of appropriate extended family to care for the child; diligence in permanency planning by child welfare; and the challenges of finding adoptive resources for older children, minority children, large sibling groups, and children who have significant behavioral and developmental problems. Longer stays in foster care are associated with a reduced likelihood of reunification and an increased number of placements. Approximately 50% of children and teenagers will experience more than one foster care placement, with approximately 25% having three or more placements. In 2010, of the 254,114 children who exited foster care, 51% returned to their parents and 14% went to a relative or guardian, whereas 21% were adopted and 11% aged out of foster care. The vast majority of the 27,854 individuals who aged out were emancipated at age 18 years. Because the long-term benefit of foster care placement is uncertain, admission to foster care is and should be difficult. Almost all children entering foster care are placed involuntarily by court order after child protective investigation. Child neglect, including lack of supervision or neglect of basic nutritional, educational, and medical needs, is the most commonly cited reason for placement. Overall, approximately 70% of admissions are for maltreatment. Teenagers tend to be placed for disruptive behaviors through either the juvenile justice system or as persons in need of supervision. Voluntary placements constitute less than 1% of admissions and often are made by families as a means of accessing treatment services for a child or teenager who has complex mental health or medical problems. Families whose children reside in foster care come from all walks of life, but financial poverty remains a pervasive common factor underlying foster care placement (>50% of children live with impoverished families before foster care). Poverty, however, extends beyond the financial to the lack of the normal, predictable, nurturing environment that promotes good developmental and emotional health. Most children have experienced childhood adversities beyond maltreatment, including exposure to significant violence in their homes (84%) or communities placement, report that of caregivers have parenting with mental health abuse or often lack have and high and are one third of birth parents to being or as children, and about the same percentage spent time in foster care. Children often have multiple caregivers before placement in foster care. of a child often with child welfare with the after have been when the child’s health and are at imminent that childhood trauma or multiple childhood and are associated with and long-term mental health, developmental, and health exposure and in the of protective the of the in a those of the involved in emotional and children entering foster care with their and adversities are children who have emotional, developmental, and health on and are but data indicate that stability in a nurturing and family promotes after childhood foster care is with and for children. high of family from the family of origin and all that is familiar is experience for many children, for children, placement in foster care may be the time they have stable placement in a foster home can promote the ongoing and to foster care may a child’s of highlights an increasing focus on involving pediatricians in supporting children in foster care. The to and of foster care to identify kinship resources at to foster care, promote and support kinship care, children in their of support American in keeping children foster care and resources for with a of independent for pediatric health states to health for children in foster care, pediatricians in the of such health improve health-care promote the of medical and health foster care system is in of providing children with nurturing families, but also complex in legislation of and but for the of foster care with which in to or child welfare by the foster care system remains by birth parents who have multiple problems, and and that appear to be in with child welfare is for and for is a complex multiple skills with Most however, more than of in many case for the biological family, parents the care of their children while to with or resources are mental health, parenting medical care, and and to promote also educational, developmental, medical, and mental health services for children, and support the foster parents in their care. birth parents are or to the for reunification, have the of supporting through the of permanency also are to children and a of to a family than their family of also and foster parents. have a with the system in their family court and the juvenile justice of a child from a family, the prepare a court the for the child or in foster care, the to court at to provide ongoing for the of placement and to their on of parents and children toward child in foster care is represented in court by a who may or may not be an on the In some states, in the court also may a special on of the who are not special many to the child’s for to the oversight with the court have the of on information to in a child remains in placement after or services for biological and at the case for a child in care to placement or an permanency is the court the permanency with the that such a is on the from all child welfare mental health and and the youth who is of age and developmental to on his or her for the child and childhood trauma remains parents are the and of the foster care system, and foster parenting is the Foster parents come from all walks of life, on tend to be be of lower have at a high be and have children of their have and most are by a to for children. foster parents with the of percentage of foster parents are and are to that can foster and 5% of foster families undergo to as resources for or children. However, most foster parents little about parenting children who have significant trauma and There are some studies that specific and for foster parents and birth parents as Foster and parenting for foster improve outcomes for children, but these have not for foster parenting are a for child in their care that is by individual The is by the child’s health needs, and the of the parenting The is to needs, and most and recent that approximately two of the of parenting a child in foster and of foster families are some of the most child welfare are in the foster care system in of and Foster families the of the for children and teenagers, but are to the system, and the birth family for the child’s care. remains with the birth a child is for but the foster care is for that a child’s needs are and the child is well of youth in foster care, reside in residential or group home placements, which can of child health services are but is The outcomes of group care have not been well and there to be in the of such of a child with his or her biological is the best for reunification, may be for the parents and The of the is Children who have been or by their parents may not in a setting. parents may not the need to focus on the child during and focus on their issues or with child parents may to the of the child with the and may which is and for children, and and the the with separation that may be for and through with by in a setting. to a or the home, the is before placement may for more with the birth but kin caregivers also may unique challenges they toward the birth are about or have to court-ordered to which the and is for of in which a mental health parents identify their child’s their child’s developmental parenting skills in parenting and to their child in an appropriate such as or still are not because such are and and is in which prepare birth parents for the stay on during the and with to the challenges associated with children may encounter adversities in foster care. in foster care placement, in or child care placement, separation from the of children entering or their foster home, by birth parents, a with their foster being or and court are but some of the children may an child, one can be to is as the of a child to foster care after reunification, placement with extended family or guardian, or adoption. on the to 30% of children to foster care, as a result of a of reunification with their birth parents. but percentage of undergo during an parents of their children in the care and of the or of can be as of a in which the the child’s the child either the age of majority or is parents to their children for more of involuntarily after at reunification have The can years, during which time but at reunification and permanency planning by federal legislation in states to a child has been in foster care for of the past and when there is reason not to the and in the with which they this federal child as a result of the of studies on childhood and placement has toward a to foster care, the is not to permanency on the of the out of foster care several Over of children adopted out of care are adopted by their foster parents, and 30% are adopted by kinship caregivers. to the most recent there were children out of foster care in 2010, of were for and resided in preadoptive children without an adoptive tend to be older, minority children, to be of large sibling groups, or to have significant emotional and behavioral problems, that to be to parents most often child welfare as an their and the reason for the of their family. some parents with child welfare either to remain with a or in that the child for the removal, whereas the of their family and for the resources that child welfare birth parents have trauma and their that have and lack the most basic of parenting and of their children may their of and welfare may children in a an foster home, or the home of a the of the court after child protective investigation. with kin caregivers is to be less the child has a with The in foster care may be with a of from child protective to health and members of the foster to foster care often are for the several a by most child welfare as a time of emotional for the and Children who have severe trauma may to behaviors that were in their but in the setting. The majority of children are by they not and or in in foster care often about they are in foster care, and children may for the of their about the of their parents and and their they will be in care, or when their parents will come for or when a will out of or parents may make they not or Other children about being in foster care, to their and of children and to foster parents and may their less birth as a in parenting or between for children and Children may not be for discharge from foster care or to a in foster care placement are for children, that a that of and for placements but include child behavior problems, foster between birth and foster parents, and a foster home may be or neglect a child’s needs, resulting in foster care is because the care is and nurturing foster a of and for the child, the child to the of family and to the The foster care placement is stable during the child’s time in care. The foster and birth and on of the The birth for at and of the services by child Child welfare the birth identify and on the family’s and the crisis that to the family’s is Children appropriate mental health and their parents in those services as the foster care experience not this in foster care are a have in foster care, whereas foster care through the juvenile justice system or are placed by a to their behaviors or to access appropriate mental health-care tend to have the placement they experience a variety of foster care time family group residential or and between foster care, home, juvenile percentage of teenagers are and have significant behavior teenagers may lack the to in or parenting teenagers are group who may be living with their children or placed from they have significant mental health issues or constitute a risk to their teenagers foster care as unaccompanied refugee having to the United from a variety of countries after or the of their majority of adolescents in foster care reside in their are is and they mental health services and adolescents in foster care have experienced childhood including maltreatment, as children in foster care. have and but their including and may be that the underlying remain in foster care are less to permanency, either through reunification or adoption. to parents or relatives, but many age out at age 18 years, or are to or placement care or group home care). to and for independent living is resources are Foster or kin families who remain in youth are their best and youth who identify and remain to foster parents, or appear to fare is about the outcomes of youth who have aged out is a of most youth have spent at one and many have an who are a decade removed from foster care are have with in and have high of mental health problems, including and studies indicate that with a of foster care are the and is the time during which the individual is to a stable in a of in and a larger of and in to in foster care, minority lack of and a lack of are outcomes of the of multiple and a of is from living in the of foster abuse and neglect, with separation and and a lack of role for result in a high prevalence of who are and to well are those foster youth who are and a multiple childhood health issues of children in foster care are in their of neglect, and and multiple childhood and childhood with the lack of protective the health of children in foster care. The defines children in foster care as children with special health-care needs because of their high prevalence of medical developmental dental problems, and behavioral, emotional, and mental health In of children in foster care have issues related to family about the health of the foster care population have to care, 30% to have at one medical and approximately have complex health problems. The for the high prevalence of health include medical neglect or lack of access to health services before foster of the to with child’s health needs, resulting in and the of childhood adversities on health. and developmental are and may be the result of the of and childhood or the result of studies report that the ongoing health of children in foster care are mental health and developmental problems. of children under age foster care with developmental in at one and to 70% of children age 5 have a mental health or behavioral are in the adversities and trauma children have experienced before foster care. that may have been in a or environment in a more setting. that significant behavioral of by developmental problems, to placement in emotional and mental health children foster care, their health not appear to improve The of the population the likelihood that they will to have access to information on admission foster care is foster parents have the of knowledge to as the health-care the foster system on to this complex most children in foster care have health in the of this also access to health-care because of in and of medical to in care may access to medical care, but mental health access for children in foster care. to support and foster parents about a child’s medical, developmental, and mental health needs and to appropriate treatment can to in placement when foster parents and requirements may and treatment and care can be is not However, has specific about who can for health-care on of a child in foster care. states, for of the guardian, who is the birth for including of In child welfare have in for and health-care should issues with their child welfare the health of the legislation states to health for children in foster care, is in in most with intensive care are because health-care the of care children children in foster care will their health-care as children who have special health-care needs in the of a pediatric medical The has a number of resources to pediatric but the of the medical home for the child in foster care are as The medical home should the health-care for children and teenagers in foster care by the on Foster from for Children and in Foster The are on the Foster was for by child mental health, and and youth in foster care. resources and may also be to pediatricians in with states and foster care for health brief of the health-care for children in foster care are listed in and should children and after to care, because often more health needs than one and they a between the and The admission health-care for all children, but for those with special health-care Children in foster care should have health-care and those for all children to all of their health developmental, educational, emotional and behavioral, and health-care encounter should include for child abuse and neglect in the placement. Foster that should be in to the children who have complex medical, developmental, or mental health problems, the may more health health is the most important health-care need of children in foster care. Children need and of mental health and to pediatric mental health of mental health-care basic should be in when and are two health needs of children in foster care. and may result in and multiple and are the most to be developmental for all children in foster care is not the pediatric should at a developmental to identify children in need of a some children developmental skills and in foster care, child who has behavioral or in should an It is that the with the child’s to that needs are and parents in most communities report that children in foster care have access to dental care, a high prevalence of significant dental are to with their health and dental to access issues for children in foster is a and in foster care. foster families have a of but the should not that they have in parenting children and teenagers who have past and ongoing In to the should issues specific to foster care, such as on the child’s parenting the of trauma on child supporting children through permanency planning, in placement, significant the need for and with birth parents to and and children should be about planning for their and with teenagers in foster care, have their to to a pediatric can foster parents the emotional while supporting an parenting for foster families and youth in foster care and can a foster care placement for a the also the birth and the child’s in these is the of the foster care with the as the case However, the pediatric medical home has an important role to play in that a child in foster care all health-care in a and that and youth in care all and in the health-care that health with child welfare to and information health-care are in are in a unique position to for in of care for children in foster care, in of the health in the can with their the and a and on in the of Children in Foster and the children and families for their and her at Pediatrics and the of for their and

Pediatrics in Review · review · 19 citationsread the source →

Clinical Presentation of Left Atrial Cardiac Myxoma

Introduction Cardiac myxoma is the most frequent “benign” tumor of the heart and presents an important diagnostic challenge (4,43,47). Myxomas may resemble many cardiovascular or systemic diseases, and can arise in any of the cardiac chambers, although 75% occur in the left atrium. Most cases of atrial myxomas are now diagnosed in living patients, allowing successful surgical extirpation (1,3,30,44,53). Before the introduction of angiocardiography in 1951, cardiac myxoma diagnosis was made only at autopsy (22). The first successful surgical removal of an atrial myxoma was performed in 1954 (35,47). In 1959, the first M-mode echocardiogram of a left atrial myxoma was reported (16). Indeed, the introduction of echocardiography has provided an important noninvasive means of diagnosis for cardiac myxomas (55). Thus, the diagnosis of small myxomas (less than 5 cm in size and asymptomatic) is becoming easier. We report here the experience of a French cardiovascular center in the clinical presentation of left atrial myxomas. The large number of patients in this series allowed us to perform an analytic, clinicopathologic study. Patients and Methods We reviewed the 112 cases of left atrial myxoma seen at 1 institution (Hôpital Louis Pradel, Lyons, France) over a 40-year period (1959–1998). In all cases the diagnosis was established before surgical removal. The patients’ medical records were reviewed, and data concerning clinical presentation, diagnostic methods, and postoperative course were collected. Histopathologic slides were reviewed for all cases by the same pathologist (RL). Other locations where cardiac myxoma occurred during that time period were the right atrium (15 cases), left ventricle (2 cases), and right ventricle (1 case). Follow-up information was obtained by contacting either the patients or the attending physicians, and a standardized questionnaire was completed for each case. Statistical analysis A chi-square test, or the Fisher exact test when required, was performed for all qualitative variables, and odds ratios (OR) with 95% confidence intervals (95% CI) were computed. For ordinal variables a Wilcoxon rank sum test was used. Data analysis was performed using SAS (Statistical Analysis System, SAS Institute Inc., Cary, NC). The variables studied in the statistical analysis were 1) sex and age, period of diagnosis (before or after echocardiography was available), delay to diagnosis (delay between the first symptoms and diagnosis), possible systematic (serendipitous) discovery; 2) size of the tumor (> or < 5 cm), tumor surface appearance (smooth or villous); 3) the main symptoms: cardiac (cardiac failure, malaise or syncope, chest pain or palpitations), embolic (cerebral, coronary, or peripheral artery), systemic (fever, weight loss, or pseudo-connective tissue disease signs), or neurologic (stroke, vertigo, epilepsy, coma, or other signs); 4) cardiac auscultation modifications (pseudo-mitral signs, “tumor plop”, nonspecific other signs); 5) possible chest X-ray abnormalities (left cardiac failure signs, cardiomegaly, pleural effusion, left atrium enlargement, visible myxoma when calcified), electrocardiogram (ECG) alterations (arrhythmias or conduction disturbances, ST-segment and T-wave shifts, left atrial hypertrophy, and nonspecific signs), or serologic test abnormalities (elevated erythrocyte sedimentation rate [ESR], anemia). Results Patient characteristics The study group included 72 women, (64% of the whole sample; median age, 53 yr; range, 23–84 yr) and 40 men (36% of the sample; median age, 58 yr, range, 5–77 yr). Forty-six patients (41% of the sample, 31 women, 15 men) were less than 50 years old, 47 (42%, 31 women, 16 men) were between 50 and 70 years, and 19 (17%, 10 women, 9 men) were older than 70. Age distribution was homogenous in men, but most female patients were between 40 and 60 years old (Figure 1).Fig. 1: Age distribution of 112 patients with left atrial myxoma. The clinical and laboratory features of left atrial myxoma in our series are presented in Table 1. The different frequencies of clinical and laboratory signs according to sex and age are detailed in Table 2. Male patients were more at risk than females for embolic complications and for neurologic symptoms; females were more at risk than males to develop systemic symptoms such as fever; younger patients (age <50 yr) had more neurologic symptoms and cardiac auscultation abnormalities than older patients (age >50 yr).TABLE 1: Clinical and laboratory features of left atrial myxoma (112 cases)TABLE 2: Frequencies of clinical and laboratory signs by sex and age*We divided the patients into 2 groups according to the pre-and post-echocardiography periods: 1) between 1959 and 1977, when the only diagnostic methods were angiocardiography and cardiac cathe-terization, only 14 patients (12.5%) underwent surgery; 2) since 1977, with 2-dimensional echocardiography use (transthoracic, then transesophageal), about 5 patients per year have undergone surgery for left atrial myxoma (98 patients, 87.5%). The sex ratio and age ranges are similar in these 2 patient groups, but other differences can be identified (Table 3). Before 1977, most patients were diagnosed on the basis of serologic or blood test abnormalities (particularly elevated ESR) and radiologic abnormalities; chest X-ray evidence of cardiac failure or left atrium enlargement was particularly prevalent in patients diagnosed before 1977 compared with those diagnosed after 1977 (p = 0.006 and p = 0.02, respectively).TABLE 3: Symptoms by year of diagnosis*Delay before surgery In our series, the time interval between symptoms onset and diagnosis (surgical removal) varied from 0 to 126 months (median, 4 mo). The median delay before surgery was 5.5 months before 1977, and 3 months after 1977; the difference is not significant. The median delay to diagnosis increased significantly when cardiac symptoms were present; there was no significant difference for the other symptoms (Table 4).TABLE 4: Delay to diagnosis by year and by principal clinical symptoms*Initial symptoms ( Figure 2) For 11 patients, the left atrial myxoma diagnosis was a mere chance, or serendipitous, discovery (“systematic findings” in Figure 2). Among these patients, in 9 cases echocardiography (8 cases) or computed tomography (CT) (1 case) was performed for another indication and allowed a diagnosis of myxoma. For 2 patients, echocardiography had been systematically performed during follow-up for surgery on a right atrial myxoma. Fig. 2: Initial symptoms of left atrial myxoma (112 cases).The most common initial symptoms of left atrial myxoma in our series were related to mitral valve obstruction: dizziness and occasionally syncope, palpitations, dyspnea, cough, pulmonary edema, or congestive heart failure were observed in 58 patients. Eight patients showed atypical paroxysmal clinical manifestations: chest pain, hemoptysis, limb claudication, thoracic noise, shortness of breath, or syncope when reclining. Embolic manifestations suggested myxoma in 18 patients. Constitutional or general systemic signs appeared as initial manifestations for 17 patients: myalgia, muscle weakness, arthralgia, fever, weight loss, fatigue, and Raynaud syndrome. Clinical features at diagnosis All patients presented with at least 1 or more symptoms of the classic triad: 1) obstructive cardiac signs; 2) embolic signs; and 3) constitutional or systemic manifestations (See Table 1). 1) Intracardiac obstruction signs occurred in 75 patients. Pulmonary edema or progressive congestive cardiac failure (dyspnea, orthopnea) were the most common symptoms (n = 48). Malaise or syncope occurred in 16 cases. Two patients experienced cardiac arrest before surgery and fully recovered after resuscitation. Other nonspecific cardiac symptoms were present in 34 patients: cough, thoracic pain, palpi-tations, myocardial infarction due to coronary embolism. Malaise, palpitations, or thoracic pain could vary with body postural changes. 2) Signs of embolism were present in 33 patients, either with 1 (n = 25) or several (n = 8) locations. Embolic locations were the central nervous system (n = 24), in 1 case in the retinal artery, the upper and lower extremities (n = 15), and the coronary arteries (n = 4). 3) Thirty-eight patients presented with systemic or constitutional symptoms. These symptoms were obviously nonspecific, including fever (n = 22), weight loss or fatigue (n = 20), and immunologic diseases mimicking symptoms such as myalgia, muscle weakness, arthralgia, or Raynaud syndrome (n = 6). 4) Other clinical presentations 4.1) Twenty-nine patients had neurologic symptoms, particularly transient or permanent motor or sensory neurologic deficiencies (n = 23), when cerebral emboli were present (stroke). Three of these patients developed multiple cerebral aneurysms, induced by cerebral emboli. Three patients had epileptic fits, or multilocular sclerosis mimicking symptoms. Six patients also suffered from other neurologic manifestations, such as vertigo or coma. One patient with streptococcal meningitis underwent surgery for a supposed antibiotic-resistant endocarditis suggested by echocardiographic findings, but surgery uncovered an incidental noninfected myxoma. 4.2) One patient had fever and positive blood cultures for Streptococcus viridans. 4.3) Three patients were investigated for liver abnormalities connected in fact with right cardiac failure. 4.4) For 3 patients, the main symptoms were abdominal pain or hemoptysis. Physical examination (cardiac auscultation) On cardiac auscultation 72 patients (64%) had abnormal findings, 18 (16%) of them with postural changes or with time examination modifications. These murmurs looked like significant mitral stenosis findings: apical diastolic or presystolic murmur (n = 60, 53%). A tumor plop was heard in 17 patients (15%), all before 1989. Other auscultatory features were changes in preexisting murmurs, gallops, or modification of the first (split) or second heart sound (n = 12, 11%). A significant was observed between cardiac auscultation abnormalities and 1) systemic symptoms (fever, weight loss or and 2) cardiac symptoms and signs (cardiac failure, (Table no between auscultatory signs and embolic or neurologic symptoms was between clinical The most frequent laboratory was in patients Table 1). in men, in was observed in 15 patients. blood or was present in patients. The between these serologic abnormalities and systemic manifestations was significant Table there was no significant between serologic signs and or neurologic symptoms. abnormalities of the patients (n = had abnormal Table 1). atrial was the most frequent (n = or or conduction were Other were ST-segment abnormalities (n = or nonspecific abnormalities (n = hypertrophy, The of abnormalities with systemic manifestations and cardiac signs was significant Table was no significant with embolic or neurologic symptoms. were abnormal in patients Table 1). included pulmonary or congestive heart failure signs (n = and nonspecific (n = atrial enlargement (n = that made the tumor visible (n = and pleural were (n = The of radiologic abnormalities with systemic and cardiac manifestations was significant Table X-ray abnormalities were significantly less frequent in patients with embolic or neurologic methods Before 1977, all cases were diagnosed by angiocardiography with left heart (n = 1977, echocardiography was the diagnostic (n = only M-mode echocardiography was (Figure 3). 2-dimensional and particularly echocardiography the methods in many cases. For 2 patients the diagnosis was established by or 3: A myxoma is seen in the left The diagnosis of myxoma was obtained after surgical tumor for all cases. On the tumor from 1 cm to 15 The size was for was than 5 cm in and in cases had been during The weight of the from 15 to In our series of the myxomas were with a cm), and were the left atrial myxomas in our series, the and from the left atrial with only a other left and small mitral valve The myxoma surface was studied in was or in of these (n = and (Figure 4) in the other cases (n = The less common or (Figure 5) myxomas had a surface that of multiple or and with a to (Figure 4: left atrial myxoma after left atrial were on the of myxoma in an of an The myxoma had a or an and a were the The surface of the tumor was by a of was observed in of the cases. We with a myxoma from with a and or different of 1) (Figure with or by then by 2) (Figure with many or in the of the cases were left atrial of them with and with were myxomas with All were observed in patients with myxoma and atrial myxoma with with myxoma in atrial myxoma with or myxoma in significant could be between myxoma size or 5 and diagnosis or or of or serologic symptoms or signs (Table 6). a myxoma size cm was significantly with cardiac symptoms, auscultatory signs, and and chest X-ray of myxomas appeared to be more and the delay to diagnosis was for small than for large Table of clinical features to myxoma size was significantly with neurologic symptoms, embolic and cardiac auscultation there was no significant between and or X-ray signs or symptoms; discovery; or delay in diagnosis (Table of clinical features to myxoma surface course All patients had patients during the 1 patient in during a second surgical for a of myxoma years after the first surgical a on in with cardiac and on the second postoperative from a in from mitral by a mitral and a in from meningitis with the the incidental tumor had been 1 patient a mitral valve endocarditis was with the myxoma. The most frequent postoperative was transient or atrial in patients A permanent cardiac for was for only 2 patients. Follow-up the postoperative patients were to patients to and not our Among the other patients, 4 and were during the follow-up Patients presented with peripheral fully The follow-up for patients with multiple cerebral is 14 years a In the present series, were for a median of 3 years 1 yr). Six patients had a of myxoma. Three patients with myxoma in the left and 17 years Three other patients had One of them suffered 2 in the left 16 and months The other 2 patients with had an initial myxoma in the right for 1 of them the was in the left atrium 3 years and for the other the were multiple in the left atrium and years and then in the right atrium years We report here the series of patients with left atrial myxoma diagnosed in a to our The patients presented over a 40-year ratio is with other in this ratio from to Myxomas can occur in all but are most frequent between the and of occur in although there is no for this female due in to In our series, younger age is significantly with neurologic signs or cardiac auscultation and is with neurologic or embolic symptoms in men and systemic symptoms in Clinical features The clinical features of these are by and there are no signs and symptoms that the of a myxoma In a of there are no symptoms at all in our there is no significant between the size of the tumor or 5 and the of discovery or atrial myxomas when the mitral or systemic 1) symptoms occur in of patients in our cases as mitral valve in mitral atrial and of fever are only of patients had in our study. Cardiac obstruction can be by progressive congestive cardiac failure on or or by syncope, or to mitral valve obstruction by the myxoma or coronary arteries The of obstruction may vary with body and these postural changes are particularly of myxoma (35,47). Cardiac failure the most frequent in our In our the of cardiac signs increased the diagnosis to that clinical symptoms are by another more common disease due to 2) emboli are the second of the classic in of myxoma patients in our study. than of emboli to the central nervous system in our but any may be to a of symptoms and cases emboli in the upper and lower coronary and more emboli may to aneurysms, as of cardiac myxomas as in 3 patients in our was 12, yr, We that the of an or surface is significantly with cerebral and peripheral 3) Constitutional signs are the of the classic these symptoms are may occur in to of cases The is lower in our series studied a at a cardiovascular These signs and symptoms myalgia, muscle weakness, arthralgia, fever, weight loss, and are obviously nonspecific and may occur in a of or or immunologic diseases tissue manifestations have also been reported in myxoma patients Cardiac auscultation Cardiac auscultatory may vary between and may on body presystolic or diastolic murmurs, significant mitral may be heard in more than of the patients in our The auscultatory of myxoma is “tumor is a heart sound of heard after the second heart sound may be with a heart sound or a mitral The tumor plop is in only of patients in our We established a significant between cardiac auscultation abnormalities and cardiac or systemic symptoms. and are abnormal in only of the patients those with systemic symptoms significant was in our The main but nonspecific laboratory abnormalities are and elevated or is or may occur by on the has also been common are and that the and of a by the tumor may be for systemic and manifestations has been with of in patients with myxoma that to after surgical removal A between the size of the tumor and the of has also been suggested have also been in myxoma tissue myxoma tissue in cases by and are nonspecific but observed in our atrial in of patients, the alterations by the is (less than of cases) in to the in mitral valve We observed a significant between signs and the of cardiac or systemic symptoms. also nonspecific features in the patients and are not for when the tumor is in our a left atrium enlargement and signs of pulmonary may be In our series, chest X-ray abnormalities were significantly with cardiac or systemic symptoms, but there were radiologic signs when the myxoma was by embolic or neurologic In cardiac signs or symptoms are more prevalent with large and may that embolic becoming are diagnosed before the the size 5 that to cardiac and radiologic data a positive between small tumor size and embolic Table 6). methods is the and diagnostic of is and not any risk of tumor and and cardiac examination may be by the echocardiography is less with an to but echocardiography the for surgery is only on echocardiographic evidence of the in our series angiocardiography has not been since coronary in patients over 40 years old is in to coronary disease Other diagnostic methods and The of and over echocardiography is that of and thoracic are also more in tumor and tumor and size data that most left atrial myxomas arise from the atrial or the on the of and on the appearance is or with a or or is and the surface is either or and in our myxomas with constitutional symptoms, or In the such as and surface are seen in older that In our series, there was no significant between and The size and weight of myxomas but in our the of symptoms was in patients with on could or myxomas and or myxomas according to the of the that all occurred in patients with and myxomas. the of cardiac myxomas have been The of most is that myxomas are of is no that myxomas are myxomas may have a of that at first may be the of multiple surface or is not with or any of presentation, and is important not to an on the basis of these atypical are cardiac not be with myxomas The to the tumor are to be and analysis has that myxoma as tumor = and are and may be for and cases with is as is the showed that was by is also a for the that myxomas arise from the to A study that myxomas with a between tumor size and the of this a in Myxomas may to the but these not have any The myxoma tissue emboli may may the and may or may but any cerebral tissue years the may to Three patients in our series had embolic that into the with of multiple aneurysms, any or during and follow-up The of for myxomas is surgical removal the diagnosis is of the tumor is Embolic complications or are in patients: of patients in the time of our series, not due to cardiac but 2 patients had cardiac arrest in the before surgery with successful resuscitation. surgery is a as most are can be The may according to In our series, was 3 patients during the postoperative period before and another patient in of meningitis not to myxoma. The most frequent postoperative was transient or with an of Cardiac myxomas occur but or cases have been The reported rate ranges from to in the in our are reported from as as a months to as as years after of the myxoma in our The of is not but risk or of tumor of the a of tumor in the In most cases of of the to be the of Patients with abnormalities are at risk of and from 2 or more of the cardiac and myxomas or of the with and are as or The risk of for and myxomas is about and is only for In our series, 3 cases the cardiac myxoma the time of myxoma patients are younger than myxoma patients. myxomas of the 2 patient groups are not A to has been identified The is In the the rate is and after of myxomas ranges from 0 to in our may surgical removal in our A patients may permanent cardiac for conduction 2 patients in our In of the of a tumor that with mitral valve to in heart failure, the mitral valve is In our only 1 patient mitral valve for endocarditis with left atrial myxoma. the myxoma patients to be and cases. echocardiogram is over the period at diagnosis The mitral valve other and heart more common than and occur in patients with myocardial infarction or systemic symptoms are present (fever, weight loss, the diagnosis heart and tissue disease or The of embolic and constitutional symptoms is due more to but may also myxoma. The of or syndrome to the 2 diseases, as these are in myxoma. myxomas are occasionally the clinical of myxoma and endocarditis more of cardiac myxomas reported 40 cases with a presentation similar to is no clinical between and noninfected myxoma cardiac symptoms and the rate of systemic or cerebral constitutional symptoms significantly in patients with myxoma (fever, elevated and men are more than series of 112 cases of left atrial myxoma clinical that this tumor may a of clinical symptoms not only such as cardiac but also or neurologic is made only on clinical there are no signs or symptoms. but or cases have been that and of the by the tumor may be for or including the is the of for diagnosis and follow-up of this myxomas are be in the diagnosis of mitral valve disease and congestive heart failure, in patients with is also for any patient with embolic embolic in in the of signs or symptoms of endocarditis or to a of myxoma as the embolic The obtained by be are to the clinical features of in in myxoma or be studied for embolic myxomas with of could be performed to for the ratio and age We a series of 112 cases of left atrial myxoma diagnosed in a French and 40 age range, yr) over 40 years, from 1959 to Symptoms of mitral valve the first of the classic of myxoma presentation, were present in 75 patients with cardiac failure or Symptoms of the second frequent presentation in the classic were observed in 33 cases with 1 or several cerebral emboli with are at risk than females of embolic The of the classic of constitutional symptoms with fever, weight loss, or symptoms tissue due to and patients have more neurologic symptoms, and female patients have more systemic symptoms. patients (64%) had cardiac auscultation valve disease and more the tumor plop The most frequent was left atrial were The number of myxoma patients diagnosed after 1977 the introduction of echocardiography as a noninvasive diagnostic there was no significant in the time from onset of symptoms to between patients seen in the before and after The tumor from 1 to 15 cm with a weight of between 15 and The myxoma surface was or in of the and in the other cases. Myxomas in patients with embolism have a those in patients with cardiac symptoms, auscultation signs, tumor and electrocardiogram or radiologic signs of left atrium and are significantly the The is and only 4 occurred our 112 cases over a median follow-up of 3 The rate is but follow-up and echocardiography are for patients. The surgical were performed during the 40-year period by We are to for the

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The Management of Preoperative Anxiety in Children: An Update

Anxiety in children undergoing surgery is characterized by subjective feelings of tension, apprehension, nervousness, and worry that may be expressed in various forms (1). Postoperative maladaptive behaviors, such as new onset enuresis, feeding difficulties, apathy and withdrawal, and sleep disturbances, may also result from anxiety before surgery. In fact, studies have indicated that up to 60% of all children undergoing surgery may present with negative behavioral changes at 2 wk postoperatively (1,2). Variables such as age, temperament, and anxiety of the child and parent in the preoperative holding area have been identified as predictors for these behavioral changes (1). Extreme anxiety during induction of anesthesia is also associated with an increase of these postoperative negative behavioral changes (3). In addition to behavioral manifestations, preoperative anxiety activates the human stress response, leading to increased serum cortisol, epinephrine, and natural killer cell activity (4,5). This stress response can be activated by many different noxious stimuli including fear, anxiety, pain, cold, major surgery, and infection. The main components of the stress system are the corticotropin-releasing hormone and the locus ceruleus-norepinephrine/autonomic systems and their peripheral effectors, the hypothalamic pituitary-adrenal axis and the limbs of the autonomic system (5). There is also evidence for a bidirectional communication between the neuroendocrine system and the immune system. Stress activates the hypothalamic pituitary-adrenal axis, increases circulating glucocorticoids, and is associated with alterations of immune function and susceptibility to infection and neoplastic disease (6). The human response to surgical stress is characterized by a series of hormonal, immunological, and metabolic changes that together constitute the global surgical stress response (7,8). This perioperative response is considered a homeostatic mechanism for adapting to the perioperative injury. The effects of the surgical stress response, however, may be detrimental: neuroendocrine hormones (e.g., cortisol, catecholamines) and cytokines (e.g., interleukin-6) provoke a negative nitrogen balance and catabolism, delay wound healing, and cause postoperative immunosuppression (7,8). Children are particularly vulnerable to the global surgical stress response because of limited energy reserves, larger brain masses, and obligatory glucose requirements (9). Because acute psychological stress, such as preoperative anxiety, is associated with immediate stress hormone release, the contribution of perioperative psychological factors to the global perioperative stress response cannot be ignored. In adults, increased preoperative anxiety is associated with poor postoperative behavioral and clinical recovery (10,11). As an indicator of the importance of preoperative anxiety, a panel of 72 anesthesiologists recently ranked various anesthesia low-morbidity clinical outcomes based on importance and frequency. The five clinical outcomes with the highest combined score were incisional pain, nausea, vomiting, preoperative anxiety, and discomfort from IV insertion (12). Thus, consensus is evident among anesthesiologists about the need to treat anxiety before surgery. In a modern epidemiological framework, diseases can be characterized in terms of risk factors, interventions, and outcomes. In this update, we will review preoperative anxiety in children using this conceptual framework (Fig. 1).Figure 1: Conceptual framework of perioperative anxiety. Revised from (72).The Psychobiology of Separation Learning to cope with separation from a parent is necessary for a child’s normal development (13). Separation experiences such as going to school facilitate normal psychological development and personality organization. Other separation experiences, such as perioperative separation, may precipitate confusion and anxiety. Between these two extremes, there are many separation experiences with varying degrees of psychobiological stress. In the first weeks of life, infants are able to discriminate among people, but will accept care and comfort from adults other than their parents (14). By 3 mo of age, however, infants begin to respond differently to familiar and unfamiliar people. Older infants smile more at familiar people and may even try to engage their attention (14). Separation anxiety usually begins at 7–8 mo of age and peaks around 1 yr of age. In part, separation anxiety represents the infant’s acquisition of new cognitive abilities and object permanence. The intensity of separation anxiety declines with age, largely because of increasing cognitive abilities and memory capacity. Frequently, however, the increase in abilities does not immunize toddlers and preschoolers against the stress and distress of separations. The extent to which separation is traumatic or evokes adaptive responses reflects an individual child’s developmental age, parenting experiences, genetic endowment, and environmental stability. For children with biologically based vulnerabilities, such as a sensitivity to novelty and transitions, even expected separations may impose a greater degree of stress than for less sensitive children (13). How parents help the child mediate a separation experience play a crucial role in the child’s acute and long-term responses. In the extreme, the parent may be unable to mediate the experience for the child because of limitations such as severe anxiety. How well children have been cared for up to the time of the separation also influences their response to the stressor. Children deprived of attention in the home are at increased risk for stress in response to separations. Thus, the extent to which separations evoke adaptive responses reflects an individual child’s genetics, personality, parenting, and previous life experiences. Preoperative Anxiety: Identification Identifying risk factors for development of preoperative anxiety is important, as more resources can be directed toward vulnerable children. Children 1–5 yr old are at the highest risk for developing extreme anxiety (1). This is not surprising considering the psychobiology of separation anxiety. Children who are shy or inhibited and those who have a high intelligence quotient and lack good adaptive abilities are also at increased risk (15). Previous surgery or hospitalization and poor response to visits to the pediatrician’s office are also predictors for the development of preoperative anxiety. Finally, parental anxiety has been identified as a predictor for increased child’s anxiety. Preoperative Anxiety: Behavioral Modalities Preoperative Preparation Programs Most studies suggest that preoperative preparation programs reduce anxiety and enhance coping in children (16). These behavioral preparation programs have evolved significantly over recent decades. In the 1960s, preparation programs were designed to provide an orientation tour and narrative information and facilitate trust between the hospital staff, the child, and the parent (16). In the 1970s, modeling techniques were developed where children indirectly experienced the perioperative course by role rehearsal using dolls or by viewing a video (17). These modeling techniques were augmented in the late 1980s with child life preparation and the teaching of coping skills (17). Currently, development of coping skills is considered the most effective preoperative preparation intervention, followed by modeling, play therapy, operating room tour, and printed material (18). Although experts favor teaching of coping skills, most preparation programs in the United States consist of an orientation tour and printed information (18). Although coping preparation has been associated with reduction of anxiety in the preoperative holding area, no differences were found among the various preparation programs during induction, in the recovery room period, or postoperatively (19). Thus, the cost-effectiveness of child life specialists may or may not be justified by an associated reduction in preoperative anxiety. Psychological preparation programs should be tailored to individual needs such as age, developmental stage, and previous experience (20). The priority of the age criterion relates to both the anxiety such exposure might generate and the length of time over which children can cope with anticipation. In addition, timing of the program before surgery is an important variable (20). Children aged ≥6 yr benefit most if they participate in a preparation program ≥5 days before surgery and benefit least if the program is given only 1 day before surgery. This phenomenon is related to the way that children in this age group process new information. Finally, a child who has previously undergone surgery or has been hospitalized may develop an exaggerated emotional response to an information-based preparation program (20). As increased parental anxiety results in increased child’s anxiety (1), there is a need for interventions that are designed specifically for parents. Cassady et al. (21) demonstrated that parental preoperative anxiety decreased after viewing an educational videotape. We suggest that more parental interventions need to be developed and that a child’s anxiety should be evaluated as an outcome. Preoperative Anxiety: Behavioral Modalities Parental Presence during Induction of Anesthesia. Parents and children prefer to stay together during medical procedures such as immunizations, dental treatment, and induction of anesthesia (22). Some data indicate, however, that parental presence during induction of anesthesia (PPIA) is allowed in 26% of US hospitals and is encouraged in only 8% of hospitals (23). In contrast, 28% of hospitals have no formal hospital policy and parental presence is against hospital policy for 32% of hospitals in the US. The smallest use of this induction technique was reported in the South-Central region and the highest in the Northwest and the Northeast (23). Interestingly, anesthesiologists from Great Britain (GB) encourage PPIA significantly more than anesthesiologists from the US (23,24). The reasons for these differences may include the use of different induction techniques, less concern about legal ramifications in GB, and a stronger demand for parental presence in GB. Economic issues such as operating room (OR) efficiency, infrastructure issues, lack of induction rooms and patchy preoperative educational programs, probably limit the availability of PPIA in the US. Potential benefits from PPIA include reducing the need for preoperative sedatives and avoiding the fear and anxiety that may occur on separation to the OR. Other benefits, such as increasing the child’s compliance during induction, remain controversial. Objections to PPIA include concern about disruption of the OR routine, crowded ORs, and a possible adverse reaction of parents. In addition, increased parental anxiety can increase a child’s anxiety, prolong anesthetic induction, and place additional stress on the anesthesiologist. Although early observational studies suggested reduced anxiety if parents were present during induction (25), more recent randomized controlled trials indicate that routine parental presence is not beneficial (26–28). One study demonstrated that only children >4 yr of age, those who have a “calm” baseline personality, or those who have a parent with a “calm” baseline personality benefit from this intervention (26). When interpreting the results of these studies, however, it should be noted that the design of a randomized controlled study does not reflect the practice of all anesthesiologists. When data of survey studies are reviewed (23,24), it is noticed that most anesthesiologists use either PPIA or sedative premedication to treat preoperative anxiety. When sedative premedications were directly compared with PPIA, however, it was found that children receiving oral midazolam were significantly less anxious and more compliant during the induction process (27). A recent study examined whether a combination of PPIA and oral midazolam is more effective than oral midazolam alone (28). The investigators found that PPIA has no additive anxiolytic effects for children who received oral midazolam preoperatively. Parents who accompany their sedated children into the ORs, however, are significantly less anxious and more satisfied both with the separation process and with the overall anesthetic, nursing and surgical care provided (28). PPIA is also associated with important legal implications. Lewyn (29) described a case in which a mother was invited to accompany her son into an emergency treatment room. According to the court, the mother fainted and suffered an injury to the head. In its verdict the Illinois Supreme Court stated that a hospital, which allows a nonpatient to accompany a patient during treatment, does not have a duty to protect the nonpatient from fainting. However, if medical personnel invite the nonpatient to participate in the treatment, then the hospital has a legal responsibility toward the nonpatient. Interestingly, some hospitals in the US now require the parents to sign a written informed consent acknowledging the risk of being present during induction of anesthesia. We believe that future research interests should shift towards an emphasis on what parents actually do during induction of anesthesia, rather than simply on their presence. Allowing a parent into an OR without significant preparation may be counterproductive because some parent behaviors, such as criticism and commands, are associated with increased distress. Effective methods of training such as parental preparation programs can be developed for enhancing the effects of PPIA. Preoperative Anxiety: Pharmacological Modalities The reported rate of use of pharmacological modalities for the treatment of preoperative anxiety in the US varies widely among age groups and geographical locations (24). Premedicant sedative drugs are least often used with children <3 yr of age and most often used with adults <65 yr of age (25% vs 75%). Currently, the most commonly used sedative premedicant in the preoperative holding area is midazolam (85%), followed by ketamine (4%), transmucosal fentanyl (3%), and meperidine (2%) (Fig. 2). TABLETABLE The majority of children in the US are premedicated via the oral route (80%), followed by the intranasal route (8%), the IM route (6%), and the rectal route (3%).Figure 2: Types of premedicants used in the preoperative holding area (23).Table 1: Premedications Administered by the Oral RouteTable 2: Premedications Administered Transmucosally and RectallyMidazolam. Midazolam is a short-acting benzodiazepine that is very lipophilic at physiologic pH, which accounts for its rapid onset of action. Davis et al. (30) has demonstrated that intranasally administered midazolam in a dosage of 0.2–0.3 mg/kg in patients undergoing myringotomies led to satisfactory separation from parents and a satisfactory induction over 70% of the time and did not prolong recovery time and hospital discharge time. Midazolam administered intranasally is effective in reducing anxiety in children within 10–12 min (31). A major drawback of intranasally administered midazolam, however, is that at least 50% of children cry on administration because it transiently irritates the nasal passages. Midazolam can also be given as a nasal spray, which is effective in reducing procedural anxiety in children undergoing cancer therapy (32). Midazolam can be administrated sublingually at the same dosage as intranasally. Although sublingual administration of midazolam is associated with a decreased incidence of crying (18%), it may be difficult to prevent small children from either swallowing the midazolam or spitting it out immediately (33). Rectal administration of midazolam in doses of 0.5–1.0 mg/kg effectively reduces the anxiety of children before induction of anesthesia (34). Although the incidence of hiccups after IV midazolam is <2%, the incidence noted that in a recent study involving rectally administered midazolam was more than 20%(34). The investigators had no explanation as to the increased rate of hiccups other than the young age of the children, but they found that the hiccups were easily treated by ethyl chloride nasal spray (34). Orally administered midazolam (0.5 mg/kg) has been shown to significantly reduce preoperative anxiety in young children (27,28). Orally administered midazolam can be given in a dosage of 0.25 mg to 1.0 mg/kg up to total dose of 20 mg depending on the of surgery and the anxiety of the A and and midazolam in a of 2 in et al. examined different doses of the midazolam and found that 0.25 mg/kg in satisfactory and in a majority of patients within 20 This study also found that increasing the dose in an increase in the of patients with satisfactory and a time to onset of Other that the time for premedicated children from their parents is min with a sedative between 20 and min The of administered midazolam and in the discharge of patients is controversial. Although recent studies noted that administrated midazolam is not associated with a discharge two studies involving children undergoing that and recovery are in the children who oral midazolam study involving children who myringotomies using or anesthesia indicated that children who were given oral midazolam experienced significant in recovery time but no in discharge time from the hospital Finally, et al. have the of a combination of preoperative oral midazolam and The investigators found that requirements by and discharge was in children who had been given midazolam preoperatively. The investigators suggested that the increased postoperative may have been to of and midazolam on As indicated a significant of children experiences maladaptive behavioral changes after surgery (1). In children who were premedicated with oral midazolam had a significantly decreased incidence of negative behavioral changes during the first after surgery However, this study noted that by 2 wk postoperatively there were no significant differences between the midazolam and The mechanism by which midazolam the incidence of postoperative behavioral changes is not but it may be related to of the perioperative process Children who received a benzodiazepine for dental and were about the experience dental than children who were not about their dental This may be particularly important for children undergoing surgical in children after oral midazolam as early as min and anxiolytic effects are as early as min after administration This timing to onset of is of importance in surgery where the of is very Midazolam and can be with which The dose in children is mg/kg given IV in a of up to 1.0 mg Some children who are with will experience it is to for can also be intranasally in a dose of given by from a is a that is very which the a good for administration and Oral transmucosal fentanyl administered in the of a to a and as the was the first sedative by the and in for use in children. Oral transmucosal in and dosage is in a and given to children in the dosage of for sedative is often associated with which usually min after children begin to the children before induction of anesthesia does however, to decreased or with induction in young children In a small of can cause a leading to significant a in be present this is administered in children is associated with a incidence of postoperative and that is not easily by In fact, at least study was because of a very incidence of preoperative A significant of is that it the postoperative et al. reported that preoperative is as effective as IV fentanyl given for of postoperative in children undergoing is an that a of and from the of ketamine compared with other premedicants is that it less given in sedative doses A of ketamine as compared with other premedicants is the of increased and which can to can also cause and in children, which can parents if they are not informed about this increased incidence of postoperative is associated with preoperative administration of ketamine The effects are all dose related and can be with the use of a small dose of administered ketamine mg/kg) the time of onset of the of administered ketamine is also dose related with administered ketamine mg/kg) an onset of of min and ketamine leading to within 20 min administration may be associated with and during the postoperative recent studies have found that use of a benzodiazepine given to children undergoing ketamine did not the incidence of In addition, the incidence of postoperative and is no different in children receiving midazolam, or a combination of ketamine and midazolam together The IV preparation of ketamine can be with or to an oral of which is by most children. can be also be given intranasally rectally and IM mg/kg) care discharge time of children who received administered ketamine is reported not to be compared with administered midazolam provided that of surgery is than min administered IM in an emergency room however, was found to significantly delay discharge and increase compared with midazolam administered rectally or intranasally et al. reported that the combination of midazolam and ketamine administrated had a rate of satisfactory compared with with either oral was also found to be to IM and in children undergoing The provided and and there was less need for IV as compared with the IM is an first developed as an but found to have and sedative Orally administrated in a dose of anesthetic and for postoperative requirements by 50% in children premedicated with This in may be to the of as well as a administered is also as effective as administered fentanyl for postoperative in children undergoing The recovery of children who is to the recovery of children who oral but significantly less postoperative as compared with One major drawback for the use of as a sedative premedicant is its onset of action. has to be administered as early as min before surgery In children, is at min for administered and min for rectally administered for the research should on the development of sedatives that will be well have a very time for onset of and have of action. In addition, developed preoperative sedatives should such as and should anesthetic requirements and reduce postoperative Finally, new methods of sedative premedications should also be For of should be as well as oral transmucosal methods for other than usually at least 1 for effective serum of drugs to be is can significantly the of a and has been effective in fentanyl in adults within min at 2 Finally, the of treatment modalities such as should be research is in these The to for review of this

Anesthesia & Analgesia · review · 408 citationsread the source →

A 5-year experience with cardiopulmonary resuscitation using extracorporeal life support in non-postcardiotomy patients with cardiac arrest.

Background: Cardiopulmonary resuscitation (CPR) using extracorporeal life support (ECLS) system has been successfully used to support patients with in- and out-of-hospital cardiac arrest (IHCA, OHCA) when conventional measures have failed. The purpose of the current study is to report on our experience with extracorporeal CPR in non-postcardiotomy patients. Methods: We retrospectively analysed a total of 85 consecutive adult patients, who have been treated with ECLS between January 2007 and January 2012. Results: The mean CPR duration was 40 min (20-70 min). The mean ECLS support duration was 49 h (12-92 h). Twenty-eight patients (33%) had ECLS related complications. Forty patients (47%) were successfully weaned and 29 patients (34%) survived to hospital discharge. Among survivors, 93% were without severe neurologic deficit. Duration of CPR was shorter for survivors than for non-survivors [(25: 20-50 min) vs. (50: 25-86 min); p=0.003]. Immediately after ECLS start, the mean blood lactate level was lower (p=0.003), and the mean pH value was higher in the survivors' group (p<0.0001) compared to the non-survivors' group. The CPR duration for the IHCA group (25: 20-50 min) was shorter compared to the OHCA group (70: 55-110min; p<0.0001). The survival rate in this group was higher compared to the OHCA group (42% vs. 15%; p<0.02). Conclusions: CPR using modern miniaturized ECLS systems should be established in the treatment of prolonged cardiac arrest and unsuccessful conventional CPR in selected patients. CPR with ECLS for OHCA has worse outcomes compared to IHCA. Duration of CPR was independent risk factor for mortality after extracorporeal CPR.

Resuscitation · 145 citationsread the source →

College student interest in teletherapy and self-guided mental health supports during the COVID-19 pandemic.

Objective The COVID-19 pandemic has worsened college students' mental health while simultaneously creating new barriers to traditional in-person care. Teletherapy and online self-guided mental health supports are two potential avenues for addressing unmet mental health needs when face-to-face services are less accessible, but little is known about factors that shape interest in these supports. Participants: 1,224 U.S. undergraduate students (mean age = 20.7; 73% female; 40% White) participated. Methods: Students completed an online questionnaire assessing interest in teletherapy and self-guided supports. Predictors included age, sex, race/ethnicity, sexual minority status, and anxiety and depression symptomatology. Results: Interest rates were 20% and 25% for at-cost supports (teletherapy and online self-help, respectively) and 70% and 72% for free supports (teletherapy and online self-help, respectively). Patterns emerged by age, anxiety symptom severity, and race/ethnicity. Conclusions: Results may inform universities' efforts to optimize students' engagement with nontraditional, digital mental health supports, including teletherapy and self-guided programs. The SARS-CoV2 (COVID-19) pandemic has taken a severe toll on public health, with effects reaching far beyond unprecedented illness and mortality. Levels of mental health difficulties appear to be rising broadly as the pandemic has progressed, both in the general U.S. population and among college students specifically.1,2 The COVID-19 pandemic and its repercussions may undermine college student mental health in myriad ways.2 Concurrently, students now face the potential for serious illness, loss of loved ones, financial strain, social isolation, loss of on-campus resources, and sudden disruption of routines-creating a "perfect storm" for the emergence or exacerbation of psychological distress.

Journal of American college health : J of ACH · 17 citationsread the source →

Mental health aspects of pandemics with special reference to COVID-19

Pandemics are large-scale outbreak of disease that spreads rapidly, afflicting many persons simultaneously across multiple countries.[1] History tells us that as humans spread across the globe so did infections. Infections have been our constant companion since antiquity. Hunters and gatherers formed tribes that turned to farming and formed villages which gradually advanced to metropolis. Urbanization brought residents into denser neighborhoods, which combined with increasing populations are placing increasing pressure on the environment. Catastrophic pandemics have been occurring since antiquity and are frequently mentioned in ancient texts. Pandemics are associated with death, destruction, and devastation. Not surprisingly, pandemics are associated with long-term psychological consequences. A brief estimate of the effects of some of these pandemics is given below. Antonine plague (AD 165) The Antonine plague (the Plague of Galen) began in the far east. Soldiers returning to Rome from the far east brought back the infection which then spread throughout the Roman Empire. The pandemic killed about five million people. Plague of Justinian (541–542) The Justinian Plague (bubonic plague) started in central Africa and spread to Egypt and then hit the Byzantine Empire and many cities around the Mediterranean Sea, spreading with ease via a large number of ships, usually maintained in unhygienic condition, arriving into the ports. The plague killed about half the population of Europe, about 25 million people. Japanese small pox epidemic (735–737) The Japanese small pox epidemic affected most of Japan. As a consequence of this epidemic, approximately 1/3rd of the entire Japanese population (about 1 million) perished.[2] The Black Death (1346–1353) The Black Death or “The Plague” is the first pandemic about which reliable information is available. This pandemic of bubonic plague originated in China in 1334, spread through central Asia and northern India following the Silk Road, and reached Sicily in 1347. Over the next 5 years, it spread throughout Europe, Russia, and the Middle East. The mortality of untreated bubonic plague is close to 70%.[3] Over 50 years, the Black Death caused about 100 million deaths.[4] In subsequent centuries, the plague caused several outbreaks through Europe in causing death and destruction but never with the same ferocity as the initial pandemic.[5] Smallpox (1519–1520) The smallpox epidemic affected the native people of Mexico. It was brought by the European invaders. In this epidemic, about 5 million to 8 million people perished.[6] Cocoliztli epidemic (1545 and 1576) The Cocoliztli (probably indigenous hemorrhagic fevers) epidemics that began in 1545 and 1576 were catastrophic and killed about 7 million to 17 million people in the highlands of Mexico.[6] The 17th-century great plagues The 17th-century “great plagues” included the Great Plague of Seville (1647–1652), the Great Plague of London (1665-1666), and the Great Plague of Vienna (1679). A total of 3 million people died due to these plagues. The Third cholera epidemic (1852) The third cholera epidemic had the highest fatality of the epidemics in the 19th century. The pandemic originated in India and spread across the world. Over a million lives were lost due to this pandemic. The third plague pandemic (1855) The third plague pandemic began with the re-emergence of the disease from its wild rodent reservoir in the Yunnan province of China in 1855. From there, the disease advanced to K'unming in 1866, the Gulf of Tonkin in 1867, and the port of Pakhoi (now Pei-hai) in 1882 and Hong Kong in 1894. From there, it spread to ports in all continents by the infected rats traveling the international trade routes on the new steamships. For the next five decades, the pandemic waxed and waned throughout the world and ended in 1959. The third plague pandemic resulted in 15 million deaths, the majority of which were in India.[7] Yellow fever (the late 1800s) Multiple Yellow fever epidemics ravaged the Americas in the late 1800s, the last ending in 1905. Yellow fever claimed over 100,000 American lives. Though exterminated from America, yellow fever continues to ravage countries in the sub-Saharan Africa and tropical South America. Flu (1889–1890) This flu pandemic occurred due to the H3N8 subtype of the influenza virus. The pandemic originated in Russia and thereafter spread across many countries in the northern hemisphere. The spread of this epidemic was facilitated by the arrival of the modern transport infrastructure. The flu resulted in about one million deaths. Sixth cholera pandemic (1910–1911) The sixth cholera pandemic also originated in India. It spread through ships and other means of transport to the Middle East, North Africa, Eastern Europe, and Russia. The pandemic claimed 8,00,000 lives. The “Spanish Flu” pandemic (1918–1920) ”Spanish Flu” Pandemic was caused by the H1N1 influenza virus. It infected more than 25% of the global population. With a mortality rate of 10%–20%, it caused 50 million, possibly 100 million deaths. The Spanish Flu caused more deaths than the Black Death did in a century.[89] Asian flu (1957–1958) The Asian flu was caused by new influenza A (H2N2) virus of avian origin. The influenza outbreak originated from Singapore, spread to Hong Kong and the eastern coast of the USA in the late 1950s and later died out after a vaccine was introduced. This influenza pandemic claimed about 1.1 million lives. Hong Kong flu (1968) The Hong Kong flu was caused by influenza A (H3N2) virus which originated from an avian influenza A virus and killed one million people. It continues to cause seasonal influenza A virus associated with severe illness in older people. HIV pandemic HIV/AIDS unlike all previous and subsequent pandemics is a slowly progressing global pandemic that has over decades affected all the continents and different populations. In addition, due to the lengthy survival of patients, it has brought a host of challenges in its wake. HIV has infected about 74.9 million individuals all over the world and about 32 million have died (end 2018) since 1981. Every year, it continues to cause about one million deaths globally.[10] Severe acute respiratory syndrome (2002–2003) The first pandemic of the 21st century was severe acute respiratory syndrome (SARS) caused by the SARS coronavirus (SARS-CoV). The condition manifested with severe respiratory symptoms and had a mortality of 10%. It began in China in November 2002 and affected fewer than 10,000 individuals in 26 countries. As a result of effective public health preventive measures worldwide, the pandemic was contained by the mid-2003.[11] For the first time during and after the SARS pandemic, the psychiatric aspects were studied all over the world. Valuable information on the psychological effects of an acute infectious pandemic on affected individuals, families, communities, health-care workers, quarantine, survivors of severe illness, etc., was gathered.[812] The H1N1 or “Swine Flu” Pandemic (2009-2010) The Swine flu began in Mexico and affected over 10% of the population of the world. It caused an estimated 20,000 to500,000 deaths.[1314] Because the disease disproportionately affected healthy young adults, often quickly resulting in severe respiratory failure, it was perceived as extremely threatening. However, the final death rate was lower than the death rates of influenza. The initial announcements and warnings by the WHO caused alarm in the general public, but this changed to distrust and disgruntlement as the predicted dire consequences of the pandemic did not materialize.[15] Governments and health agencies were blamed for panic (”panicdemic”) and pushing vaccines without adequate study to enhance the profits of pharmaceutical firms at the cost of the general public (H1N1 vaccines worth 1.5 billion dollars were administered in 2009 in the USA alone).[816] The COVID-19 pandemic The pandemic caused by novel CoV (COVID-19) began in Wuhan in China and has spread to 215 countries. It has already affected 7,000,000 individuals and killed 313,636. The virus is more transmissible than SARS-CoV and has a case fatality rate of 2.3%.[17] A unique feature of this pandemic is the accompanying “infodemic”– an excess of (mis) information on social media and elsewhere – which is a major hazard to mental well-being during this health crisis.[18] PSYCHOLOGICAL FACTORS IN PANDEMICS Despite their periodic occurrence and devastating consequences, surprisingly, pandemics have evoked minimal interest in mental health professionals, though the situation has vastly improved in the past decade. Psychosocial stressors in pandemics Pandemics are almost invariably characterized by ambiguity, misunderstanding, and a feeling of urgency.[19] As the causative agent is usually new, in the early stages of a pandemic, there is widespread ambiguity about the chances and effects of becoming infected, along with lack of information and understanding about the most effective mode of prevention and treatment.[20] Other psychosocial stressors related to pandemics include threats to the health of self and loved ones, lockdowns, social distancing, separation from family and friends, death of loved ones, social isolation due to quarantine, shortages of food and medicines, loss of earnings, closure of educational institutions and industries, and cancellation of functions and festivals.[2122] Importance of psychological factors during pandemics The current methods for combating pandemics are largely behavioral or educational interventions comprising of risk communication, vaccination adherence programs, personal protective measures, and social distancing. Extreme psychological distress related to actual or threatened infection is a significant issue. Psychological factors are also essential for understanding and combating the collective disorderly behavioral patterns displayed by people facing widespread, serious infection. Effects of stressful life events and negative emotions on the immune system Stressful life events and negative emotions suppress the immune system to some degree, resulting in enhanced susceptibility to infection.[23] Although the mechanisms of these effects are not exactly known, research has shown that stressors and negative emotions influence the production of lymphocytes and pro-inflammatory cytokines.[23] On the other hand, psychotherapeutic interventions such as cognitive behavioral therapy by decreasing a person's stress proneness and negative emotions, may reduce stress-related immunosuppression.[24] The frantic chase for quack remedies and traditional therapies A serious threat to the health of self or loved ones can impair the person's ability to make rational decisions.[25] At the beginning of a pandemic, reliable vaccines and medical treatment are often not available. In this scenario, to protect themselves and their loved ones, people in desperation turn to quack remedies and dubious traditional therapies. Traditional remedies for influenza include inhalation of vapors of carbolic acid, wearing necklaces of garlic, and drinking pine tar. Folk remedies for SARS included diets of turnips, vinegar, kimchee, or spicy foods, and even smoking cigarettes, all of which were ineffective. We may add cow's urine to this list. During the SARS pandemic, some people in China hired sorcerers, lit firecrackers, and burned fake money. People take large doses of vitamins or herbal supplements in the hope that this will boost their immunity.[2226] Civil unrest, rioting, and violence Widespread sickness, debility, and death during pandemics evoke prosocial, affiliative, supportive, behaviors in the form of mutual aid such as running community kitchens, ambulance services, or disposal of dead bodies.[27] However, civil unrest or riots have sometimes erupted during pandemics.[28] There are numerous examples of groups of citizens clashing violently with health workers, due to fears that the health workers were harming rather than helping them.[22] During the Ebola outbreak in September 2014, eight health-care workers and journalists reached the Guinean village of Worme to teach the villagers how to protect themselves against Ebola. But, the villagers, believing that the workers were spreaders of the disease, attacked and killed them.[29] Villagers in Zhejiang province of China protesting the local government's SARS policy attacked officials and broke windows and furniture of the local offices.[26] The recent attack on health-care workers in Indore and other parts of India can be added to the list. Psychological reactions to stress, harm, and loss in pandemics The majority of people are resilient to stress, and this may be more true for people from developing countries. Many persons who survive major stressful events do not suffer adverse psychological effects. Experience of the recent past however tells us that the psychological effects of pandemics are often larger than the medical effects. For instance, during the West African Ebola outbreak (2014–2015), the “epidemic of fear” affected more people than the epidemic itself.[2230] Similarly, during the 2003 SARS pandemic, the psychological morbidity greatly exceeded the medical morbidity in terms of both the number and duration of impact.[3132] Reactions of people to the stress of pandemic vary from fear to indifference to fatalism.[33] At one end of the spectrum are people who blatantly disregard the risks and refuse to follow the recommended health behaviors including hygiene practices, social distancing, and vaccination. At the opposite end of the spectrum are people who develop intense anxiety or fear. Psychologically, a moderate level of anxiety motivates people to address health threats, but severe anxiety is incapacitating.[22] Studies conducted during the early stages of the Swine flu pandemic that of a community had significant of American some of anxiety about becoming of residents of that were about the health of their family to were not about the infection measures, and on a People had of fear even at of social media was associated with anxiety and behaviors in people had more fear for the of their in by the included more frequently and to health-care out in and stress symptoms were in in perceived stress in anxiety in in and in of the the were associated with recent stressful life a and of and syndrome were associated with quarantine, more than was associated with perceived stress, and Death of a loved one due to COVID-19 was associated with perceived stress, and During from the infected individuals, health-care workers are also This has manifested in their who are health-care workers, to their psychosocial stressors may or psychiatric including anxiety and stress or loss of loved ones in the pandemic may be by or a to widespread including the deaths of loved ones in the pandemic, may result in As a pandemic the general public to the threat and anxiety is However, in individuals, the adverse psychological effects can be severe and of pandemics The of a pandemic is by an for and from the the of developing a new vaccine is and the vaccine will not be it is the This be by Similarly, the of new is also and without is with against the to stressful as At the media that reliable information about the pandemic is for the general At the beginning of an epidemic, measures to that be time for the medical and pharmaceutical are the The of interventions for rates individuals and the virus are quarantine, social distancing, and the The public health during a pandemic is to the outbreak at the with minimal risk is for this of information by the general public to about to themselves from the infection. During a pandemic, and distrust of This can be by in the media and fake in social and through and is However, this is than in the beginning of a pandemic, there is a of information about the causative agent and its During the CoV pandemic in the media the of the This resulted in public of the government's on the of with a of time and the of symptoms was It was also after a of individuals who did not develop symptoms of the disease develop the disease spread the on this the was first in in of new to the were to for on a the to its during the Black the of spread throughout from also the infected, the and their close to the community spread of the infectious this continues to be a and public health to infectious measures measures that are usually recommended include with and and that are frequently and such as and are to the general public, of is Despite the of that individuals frequently do not follow are not by individuals who themselves as a risk of infection are to to be and to be isolation due to social is also by social closure can the spread of infection. from of due to to The due to is a more that of the The for is that by greatly decreasing at in the will reduce of resulting in a of the of and an to the in India the of COVID-19 was the same as in other countries without a that at this the infection spread from 100 people to million persons in A of the epidemic was predicted in that our health system was As a result of the the time to 8 which us an to our health infrastructure. The of the one was is a it and will not as is by the increasing or has been in countries. The and most have been by by and The USA and the have China Wuhan quarantine, but later it to 15 other with include South and The of are available. was a then it be that in countries that did not the our some countries with did have are in countries that did not even has given against total on from Wuhan a to the consequences of of the along with social on the pandemic. that in to reduce the epidemic and the and be the of social in the by the and then the entire without in the a is to be to a of with people and that COVID-19 is spreading There is even of to the be given the of and the of the of is the not the virus but is more to the people from and reactions to The and total on India due to the COVID-19 pandemic caused to our lives. The loss of over our lives and our may of and The to may in five stages including the and total in their loss of a result of to the new a result of and and hope stages are almost the stages of both are by an of It be that this is not a and the reactions of individuals to a some people will and most people are in these stages of the are not in of and people may even back and the stages the final and most of effects of People severe stress and in isolation may symptoms of psychological stress and and including and is a major of the of some the and to and of this can a of and a mental People with may develop symptoms due to to the stress of persons with psychiatric such as and such as may suffer from an or of This also be due to lack of their invariably to social which to and a general of fear and that may and in to psychiatric The fear of themselves or their loved ones to COVID-19 is a and may a mental in population. The in in and fake on social media to the anxiety and that is to mental Psychological effects of loss of of is one of the most and events a has to from the risk of and disease, the loss of a of or and family loss in an a of in and social It a loss of with an and persons with an has been and may be by a of from has been including the with of for an of time and of which is and the is time the death, for is to to life without the and is on a long-term and the of are and with ability to in and its factors for include loss of and adverse of the and the of different for in the of factors for include social and or A study of people that and of the had and anxiety individuals with anxiety and had such as and However, loss has long-term effects. of the consequences of loss on well-being during 3 to 3 after loss that the to loss is not a and are by a that the of a that on an an after loss and not to even after the which is in with In to multiple patterns of that with this with long-term in the in in to loss was for the majority of individuals to by 1 after of pandemics in A ability to to a pandemic on the and of its institutions and also the and behaviors of its The of an is by of of of of and also the of During the COVID-19 pandemic, that with had the rate of in COVID-19 for population and also the deaths for and these of the and institutions that behaviors that and citizens who the have The psychological reactions of people to pandemics are to and not Reactions of people to the stress of pandemic vary from fear to indifference to At one end of the spectrum are people who blatantly disregard the risks and refuse to follow the recommended health At the opposite end of the spectrum are people who develop intense anxiety or fear. Although the majority of the population are resilient to the stress of many health anxiety and and some develop psychiatric including anxiety and As a pandemic the general public to the threat and anxiety is However, in individuals, the adverse psychological effects can be severe and as a so that the treatment not than the

Industrial Psychiatry Journal · editorial or comment · 33 citationsread the source →

Social representation and practices related to dementia in Hai District of Tanzania.

Background: With the increasing number of people surviving into old age in Africa, dementia is becoming an important public health problem. Understanding the social dynamics of dementia in resource-poor settings is critical for developing effective interventions. We explored the socio-cultural beliefs surrounding dementia and the life experience of people with dementia (PWD) and their caregivers in the Hai District of Kilimanjaro, Tanzania. Methods: Cross-sectional qualitative design. Forty one PWD were purposively sampled from the Hai District of Kilimanjaro. Twenty five paired interviews with PWD and with caregivers, and 16 with caregivers alone, were conducted. Interviews were tape recorded, transcribed verbatim and analyzed using content analysis approach. Results: Forty one PWD (26 females), aged 70 years and older, were recruited but due to speech difficulties only 25 participated in the interviews. Married were 13, widow in 22 and widower 6. The majority, 33/41 were illiterate. PWD and carers perceived memory problems as a normal part of ageing. Dementia was commonly referred as "ugonjwa wa uzeeni" (disease of old people) or memory loss disease. The majority of PWD 13/12 and carers 7/16 did not know what dementia is or what causes it. Dementia was felt to be associated with stroke, high blood pressure, diabetes, old age, curse/witchcraft and life stress. Half of the participants had used modern care and alternative care such as herbs, prayers or traditional healers. Caregivers complained about the burden of caring for PWD and suggested that community organizations should be involved in addressing the problem. Conclusions: Knowledge about dementia is low and the symptoms are accepted as a problem of old age. PWD and carers demonstrate pluralistic behaviour in seeking help from modern care, prayers and traditional healers. The disease adds significant burden to family members. Family and caregivers need more education on early recognition of symptoms and cost effective management of dementia at family level. Faith-based organizations could play an important role in dementia interventions. At a national level effective policy and improvement of the health care system to address the needs of PWD and their families are imperative.

BMC public health · 55 citationsread the source →

Pre-Migration Trauma Exposure and Mental Health Functioning among Central American Migrants Arriving at the US Border.

In recent years, increasing numbers of families and individuals have arrived at the U.S. border from Central America, in particular, from Honduras, El Salvador, and Guatemala. This study sought to examine pre-migration trauma exposure and current mental health functioning of migrant families arriving at the U.S. border from the Northern Triangle region, with specific attention to the reasons offered for leaving their home country and the frequency with which migrant families appear to satisfy legal criteria for asylum We interviewed 234 adults in McAllen, Texas, using a structured interview and standardized questionnaires to assess exposure to trauma prior to migration, reasons for leaving their home country and symptoms of posttraumatic stress and depression. We found that 191 participants (83%) cited violence as a reason for fleeing their country, 119 individuals (69%) did not report the events to the police out of fear of gang-related retaliation or police corruption, and 90% (n = 204) reported being afraid to return to their native country. Based on self-report symptom checklists, 32% of the sample met diagnostic criteria for PTSD (n = 51), 24% for depression (n = 36), and 17% for both disorders (n = 25). Examining these data against the criteria for asylum in the U.S., we found that 70% of the overall sample (n = 159) met criteria for asylum, including 80% of those from El Salvador, 74% from Honduras, and 41% from Guatemala. These findings suggest that the majority of Central American migrants arriving at the U.S. border have significant mental health symptoms in response to violence and persecution, and warrant careful consideration for asylum status.

PloS one · 54 citationsread the source →

The association between parent stress, coping and mental health, and neurodevelopmental outcomes of infants with congenital heart disease.

Caring for the complex needs of a child with congenital heart disease (CHD) can place significant burden on the family. Parent mental health and coping have important influences on resilience and neurodevelopmental outcomes in children with CHD. Objectives: To describe the uptake of a cardiac neurodevelopmental program (CNP), examine parent mental health and coping specific to parenting a child with CHD, and explore the relationship between parent mental health and child neurodevelopmental outcomes. Method: Implementation and uptake of the CNP was examined, and forty-four parents of children with CHD completed the DASS and RSQ-CHD. Results: The CNP showed significant uptake in follow-up and interventions offered including 100% completed brain MRIs of eligible patients, 35% increase in neonatal neurology consults, and 100% of families counselled on neurodevelopmental outcomes. A significant proportion of parents endorsed moderate/severe levels of anxiety (25%), depression (20%), and CHD-specific stress. Parents predominantly engaged in secondary control engagement coping (F(2,64)=75.04, p<.001, ηp2=.70). Secondary control engagement coping was associated with lower parent total stress (r=-.48, p=.006) and anxiety (r=-.47, p=.009). Higher parent stress was associated with higher anxiety (r=.45, p=.016), depression (r=.37, p=.05), more severe types of CHD (r=.35, p=.048), older child age (t(30)= -2.33, p=.03), and lower child cognitive scores (r=-.37, p=.045). More severe types of CHD were associated with lower language scores (F(3,35)=3.50, p=.03). Conclusions: This study highlights the relationship between parent mental health and early child cognitive outcomes in CHD and helps inform models of psychological care to reduce family burden and improve child outcomes.

The Clinical neuropsychologist · 44 citationsread the source →

Two decades of psychological adjustment of donor-conceived offspring of lesbian parents: examining donor contact and type.

Research question: How stable is psychological adjustment in donor-conceived offspring of lesbian parents over 21 years, considering developmental stages, donor type and impact of donor contact? Design: Data were drawn from the US National Longitudinal Lesbian Family Study, a cohort of 70 donor-conceived offspring (71.43% heterosexual, 90.00% White) assessed across four developmental stages - childhood (age 10 years, Wave 4), adolescence (age 17, Wave 5), emerging adulthood (age 25, Wave 6) and established adulthood (ages 30-33, Wave 7). From parental reports, 34.29% had an anonymous donor, 34.29% a known donor and 31.43% an open-identity donor. At Waves 4 and 5, parents completed the Child Behavior Checklist to assess their child's psychological adjustment, while at Waves 6 and 7 the offspring assessed their psychological adjustment by completing the 120-item Achenbach Adult Self-Report. Growth curve models, stability coefficients and developmental pathway analyses explored trajectories by donor type, while a multivariate analysis examined differences by donor contact. Results: Across donor types, internalizing, externalizing and total problem behaviours showed low relative but high absolute stability, with fluctuations below clinical thresholds. Externalizing and total problem behaviours declined from childhood to adolescence, increased in emerging adulthood and stabilized in established adulthood. Donor type and contact did not significantly impact behavioural outcomes. Over 80% of offspring consistently scored within the normal range across all stages. Conclusions: Findings underscore the psychological resilience of donor-conceived offspring of lesbian parents, irrespective of donor type or contact. This challenges assumptions about donor-related effects on adjustment, highlighting the importance of family relationships. Flexible, family-centred support and consideration of evolving genetic-linking technologies are recommended for policy-makers and practitioners.

Reproductive biomedicine online · 4 citationsread the source →

The psychophysiological mechanisms of alexithymia in autism spectrum disorder.

Accumulating evidence indicates that co-occurring alexithymia underlies several facets of the social-emotional difficulties common in individuals with autism spectrum disorder. The mechanisms involved, however, remain poorly understood because measuring alexithymia relies heavily on self-report. To address this issue, carefully matched groups of individuals with autism spectrum disorder and comparison participants rated 70 emotion-inducing pictures on subjectively experienced arousal while skin conductance responses were monitored objectively. The results demonstrated reliable correlations between these subjective and objective measures, and in both groups, around 25% of individual differences in this correlation (i.e. in emotion-relevant interoception) were accounted for by self-reported alexithymia. In the context of the wider literature, this suggests that alexithymia involves a disruption in how physiological arousal modulates the subjective experience of feelings in those with and without a diagnosis of autism spectrum disorder. Since mindfulness-based therapies foster greater awareness of thoughts, feelings and bodily sensations, the findings also have implications for how the symptoms and consequences of alexithymia (e.g. anxiety) might be ameliorated.

Autism : the international journal of research and practice · 84 citationsread the source →

Hope-Colored Glasses: Perceptions of Prognosis Among Pediatric Oncology Patients and Their Parents.

Purpose: Cancer patients' belief about prognosis can heavily influence medical decision making and goals of care. It is known that parents of children with cancer tend to be optimistic regarding their child's prognosis; however, little is known about pediatric patients' prognostic beliefs, how physicians' prognostic communication is perceived, and how these perceptions are compared with actual prognoses. Patients and methods: An original survey was administered to 100 pediatric oncology patients, age 10-18 years, and their parents from 2013 to 2015, at St Jude Children's Research Hospital. Patients were eligible for inclusion if they had an oncologic diagnosis, were between 1 month and 1 year from diagnosis, and were English speaking. Survey responses regarding perceived prognosis were compared with actual prognoses as determined from the medical record review and published literature. Analysis included descriptive statistics and association tests. Results: Nearly half of participants (patients = 48.9%, parents = 50.5%) displayed prognostic optimism as compared with the determined objective estimate of curative potential. The majority of both patients (78%) and parents (85%) reported belief in a very high chance of cure, although fewer reported that their physician communicated a very high chance for cure (patients = 57%, parents = 70%), and only 43% were determined to have a very high probability of cure. Significant differences were noted in prognostic optimism by cancer type (P < .0001); patients with solid tumor were more often optimistic (n = 25, 83.3% optimistic; n = 5, 16.7% accurate), and patients with lymphoma were most often accurate (n = 2, 8.7% optimistic; n = 21, 91.3% accurate). Conclusion: Pediatric oncology patients and parents tend to be optimistic about their chance of cure, as compared to both perceived prognostic communication from physicians and objective estimated prognosis. Understanding the nature of prognostic optimism among patients with cancer and caregivers may empower clinicians to guide realistic decision making while supporting hope.

JCO oncology practice · 19 citationsread the source →

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0-13·6) incident cases of stroke, 101 million (93·2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6·55 million (6·00-7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8-12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1-6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0-73·0), prevalent strokes increased by 85·0% (83·0-88·0), deaths from stroke increased by 43·0% (31·0-55·0), and DALYs due to stroke increased by 32·0% (22·0-42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0-18·0), mortality decreased by 36·0% (31·0-42·0), prevalence decreased by 6·0% (5·0-7·0), and DALYs decreased by 36·0% (31·0-42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0-24·0) and incidence rates increased by 15·0% (12·0-18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5-3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5-3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57-8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97-3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01-1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7-90·8] DALYs or 55·5% [48·2-62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3-48·6] DALYs or 24·3% [15·7-33·2]), high fasting plasma glucose (28·9 million [19·8-41·5] DALYs or 20·2% [13·8-29·1]), ambient particulate matter pollution (28·7 million [23·4-33·4] DALYs or 20·1% [16·6-23·0]), and smoking (25·3 million [22·6-28·2] DALYs or 17·6% [16·4-19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation.

The Lancet. Neurology · 5441 citationsread the source →

The effectiveness of internet-based e-learning on clinician behavior and patient outcomes: a systematic review protocol.

Review question/objective: The objective of this systematic review is to identify, appraise and synthesize the best available evidence for the effectiveness of internet-based e-learning programs on health care professional behavior and patient outcomes. Background: Technological innovation has not only impacted social change in recent years but has been the prime driver of educational transformation. The newest consumers of post-secondary education, the so-called 'digital natives', have come to expect education to be delivered in a way that offers increased usability and convenience. Health care professionals (HCPs) in the clinical setting, particularly those in rural and remote communities, are no different. Today's health workforce has a professional responsibility to maintain competency in practice through achieving a minimum number of hours of continuing professional development. Consequently, HCPs seeking professional development opportunities are reliant on sourcing these independently according to individual learning needs. However, difficulties exist in some health professionals' access to ongoing professional development opportunities, particularly those with limited access face-to-face educationdue to geographical isolation or for those not enrolled in a formal program of study. These issues challenge traditional methods of teaching delivery; electronic learning (e-learning) is at the nexus of overcoming these challenges. The term e-learning originated in the mid-1990s as the internet began to gather momentum. Electronic learning can be broadly defined as any type of educational media that is delivered in an electronic form. Terms such as computer-assisted learning, online learning, web-based learning and e-learning are often used synonymously but all reflect knowledge transfer via an electronic device. This broad definition allows for a gamut of multimedia to be used for the purpose of constructing and assessing knowledge. Multimedia typically used in e-learning range from the now archaic Compact Disc Read-Only Memory (CD-ROMs), to the simple Microsoft PowerPoint, or the more advanced and complex virtual worlds such a second life. Electronic learning can be delivered in asynchronous or synchronous formats, with the latter (for example interactive online lectures via platforms such as BlackboardCollaborate or WebEx) more commonly used in formal educational settings according to set timetables of study. Person-to-person interactivity is an important enabler of knowledge generation and while functionalities such as web 1.0 (discussion board and email) and more recently web 2.0 (Wikis and blogs) allow for this to occur both synchronously and asynchronously, it is usually utilized in formal educational contexts only. However, the economy of formal education does not allow for free access to courses which proves challenging for HCPs seeking quality educational opportunities who choose not to undergo a formal program of study or are just looking to meet a specific learning need. Alternatively, asynchronous e-learning is a more learner-centred approach that affords the opportunity to engage in learning at a time and location that is convenient and enables the learner to balance professional development with personal and work commitments. These learning opportunities are self-directed and do not require a human to facilitate learning, rather, technology officiates/facilitates the learning process and, in the asynchronous e-learning context, the learner negotiates meaning independently. Health-related e-learning research has focused on several domains including media comparative designs, self-efficacy, user satisfaction, instructional design, knowledge outcomes, clinical skills development, and facilitators/barriers to its use. The benefits of e-learning are well documented in terms of increased accessibility to education, efficacy, cost effectiveness, learner flexibility and interactivity. However, some fundamental methodological and philosophical flaws exist in e-learning research, not least the use of comparative design studies. Comparison between e-learning and traditional teaching methods are illogical and methodologically flawed because comparison groups are heterogeneous, lack uniformity and have multiple confounders that cannot be adjusted for. As early as 1994, researchersin computer-assisted learning were citing these limitations and called for a fresh research agenda in this area. Cookrepeated this call in 2005 and again in 2009 and noted a paucity of research related to patient or clinical practice outcomes. Electronic learning is not an educational panacea and research needs to progress from pre- and post-interventional and comparative designs that evaluate knowledge increases and user satisfaction. It is time to move towards determining whether improved self-efficacy or knowledge gained through e-learning improves patient outcomes or influences clinical behavior change and whether these changes are sustained. In order to develop the empirical evidence base in e-learning, research needs to be guided by established theoretical frameworks and use validated instruments to move from assessing knowledge generation towards improving our understanding of whether e-learning improves HCP behavior and more importantly, patient outcomes. One suitable framework that is congruent with e-learning research is Kirkpatrick'sfour levels of evaluation. Kirkpatrick's model is hierarchically based with level one relating to student reaction and how well the learner is satisfied with the education program. Level two pertains to learning and the evaluation of knowledge, level three expands on this and considers whether the education has influenced behavior. In the context of this review, behavior change is any practice that is intrinsically linked with the outcomes of the e-learning program undertaken. Finally, level four evaluates the impact on outcomes such as cost benefit or quality improvements. The majority of e-learning research has focused on participant experience and knowledge acquisition, outcomes that correspond with the first two levels of Kirkpatrick's model. To date, few studies have examined the effectiveness of internet-based e-learning programs on HCP behavior, which aligns with Level 3 of Kirkpatrick's model. Studies exist that use self-reported measures of intention to change behavior, however self-reported intention to change does not necessarily translate into actual behavior change. Studies that have not used self-reported measures of behavior change have used objectively measured evaluation criteria including objective structured assessment of technical skills (OSATS) using various methods including simulation task trainers and clinical simulations using standardized patients scored by a panel of experts using standardized assessment tools. Carney et al. used a national reporting and data system to measure the impact of a single one hour e-learning program undertaken by radiologists (n=31) aimed at reducing unnecessary recall during mammography screening. Carney et al. reported a null effect and attributed this to the complexities of behavior change, suggesting that longer term reinforcement of principles relating to mammography recall was required to effect behavior change. These findings also suggest that a multi-modal intervention may be required in order to reduce excessive recall rates in this area, rather than a single intervention. Contrary to Carney et al., Pape-Koehler et al. and Smeekins et al. reported positive findings using randomized controlled designs to test the efficacy of e-learning interventions on individual's surgical performance and the detection of child abuse, respectively. Pape-Koehler et al. used a 2x2 factorial design to demonstrate that an e-learning intervention significantly improved novice surgeon (n=70) surgical performance of a laparoscopic cholecystectomy (change between pre-post test OSATS p 0.001) when used in isolation or in combination with a practical training session compared to practical training alone. Smeekins et al. demonstrated that a 2 hour e-learning program improved nurses' (n=25) ability to detect child abuse in an emergency department. The nurses in the intervention (n=13) group demonstrated significantly better (p=0.022) questioning techniques and consequently, higher quality history taking, to determine children at risk of child abuse when compared with the control group who received no training at all. These three exemplar studies demonstrate the broad range of applications e-learning has in HCP education, as each study used different designs, had different subject areas and target health care professionals. This reflects the conceptual and practical challenges of the area of research that addresses levels three of Kirkpatrick's model. For this reason, the e-learning research agenda in health should focus on whether knowledge generated through e-learning is able to be re-contextualized into clinical practice, and influence sustained clinical behavior change and patient outcomes.A preliminary search of PubMed, CINAHL, The Cochrane Library, The JBI Database of Systematic Reviews and Implementation Reports, ERIC and PROSPERO was conducted to determine if a systematic review on the topic of interest already existed. This search identified four systematic reviews that specifically reviewed outcome measures of knowledge and skill improvement in the domain of e-learning. Two examined research conducted in nursing, with the other two in orthodontics. Lahti et al. systematic review examined the impact of e-learning on nurses' and nursing students' knowledge, skills and satisfaction. Lahti et al. were unable to demonstrate a statistical difference between cohorts undertaking e-learning compared to conventional teaching methods, findings that were not replicated by Du et al. This may be due to the decision by Lahti et al. (ABSTRACT TRUNCATED)

JBI database of systematic reviews and implementation reports · 118 citationsread the source →