Search the source libraries

First-Episode Services for Psychotic Disorders in the U.S. Public Sector: A Pragmatic Randomized Controlled Trial.

Objective: This study sought to determine the effectiveness of a comprehensive first-episode service, the clinic for Specialized Treatment Early in Psychosis (STEP), in an urban U.S. community mental health center by comparing it with usual treatment. Methods: This pragmatic randomized controlled trial enrolled 120 patients with first-episode psychosis within five years of illness onset and 12 weeks of antipsychotic exposure. Referrals were mostly from inpatient psychiatric units, and enrollees were randomly allocated to STEP or usual treatment. Main outcomes included hospital utilization (primary); the ability to work or attend age-appropriate schooling-or to actively seek these opportunities (vocational engagement); and general functioning. Analysis was by modified intent to treat (excluding only three who withdrew consent) for hospitalization; for other outcomes, only data for completers were analyzed. Results: After one year, STEP participants had less inpatient utilization compared with those in usual treatment: no psychiatric hospitalizations, 77% versus 56% (risk ratio [RR]=1.38, 95% confidence interval [CI]=1.08-1.58); mean hospitalizations, .33±.70 versus .68±.92 (p=.02); and mean bed-days, 5.34±13.53 versus 11.51±15.04 (p=.05). For every five patients allocated to STEP versus usual treatment, one additional patient avoided hospitalization over the first year (number needed to treat=5; CI=2.7-26.5). STEP participants also demonstrated better vocational engagement (91.7% versus 66.7%; RR=1.40, CI=1.18-1.48) and showed salutary trends in global functioning measures. Conclusions: This trial demonstrated the feasibility and effectiveness of a U.S. public-sector model of early intervention for psychotic illnesses. Such services can also support translational research and are a relevant model for other serious mental illnesses.

Psychiatric services (Washington, D.C.) · randomised controlled trial · 96 citationsread the source →

Telephone-Based Cognitive Behavioral Therapy for Insomnia in Perimenopausal and Postmenopausal Women With Vasomotor Symptoms: A MsFLASH Randomized Clinical Trial.

Importance: Effective, practical, nonpharmacologic therapies are needed to treat menopause-related insomnia symptoms in primary and women's specialty care settings. Objective: To evaluate the efficacy of telephone-based cognitive behavioral therapy for insomnia (CBT-I) vs menopause education control (MEC). Design, setting, and participants: A single-site, randomized clinical trial was conducted from September 1, 2013, to August 31, 2015, in western Washington State among 106 perimenopausal or postmenopausal women aged 40 to 65 years with moderate insomnia symptoms (Insomnia Severity Index [ISI] score, ≥12) and 2 or more daily hot flashes. Blinded assessments were conducted at baseline, 8, and 24 weeks postrandomization. An intent-to-treat analysis was conducted. Interventions: Six CBT-I or MEC telephone sessions in 8 weeks. Participants submitted weekly electronic sleep diaries and received group-specific written educational materials. The CBT-I sessions included sleep restriction, stimulus control, sleep hygiene education, cognitive restructuring, and behavioral homework; MEC sessions provided information about menopause and women's health. Main outcomes and measures: Primary outcome was scores on the ISI (score range, 0-28; scores ≥15 indicate moderate to severe insomnia). Secondary outcome was scores on the Pittsburgh Sleep Quality Index (score range, 0-21; higher scores indicate worse sleep quality). Additional outcomes included sleep and hot flash diary variables and hot flash interference. Results: At 8 weeks, ISI scores had decreased 9.9 points among 53 women receiving CBT-I (mean [SD] age, 55.0 [3.5] years) and 4.7 points among 53 women receiving MEC (age, 54.7 [4.7] years), a mean between-group difference of 5.2 points (95% CI, -6.1 to -3.3; P < .001). Pittsburgh Sleep Quality Index scores decreased 4.0 points in women receiving CBT-I and 1.4 points in women receiving MEC, a mean between-group difference of 2.7 points (95% CI, -3.9 to -1.5; P < .001). Significant group differences were sustained at 24 weeks. At 8 and 24 weeks, 33 of 47 women (70%) and 37 of 44 (84%) in the CBT-I group, respectively, had ISI scores in the no-insomnia range compared with 10 of 41 (24%) and 16 of 37 (43%) in the MEC group, respectively. The CBT-I group also had greater improvements in diary-reported sleep latency, wake time, and sleep efficiency. There were no between-group differences in frequency of daily hot flashes, but hot flash interference was significantly decreased at 8 weeks for the CBT-I group (-15.7; 95% CI, -20.4 to -11.0) compared with the MEC group (-7.1; 95% CI, -14.6 to 0.4) (P = .03), differences that were maintained at 24 weeks for the CBT-I group (-22.8; 95% CI, -28.6 to -16.9) and MEC group (-11.6; 95% CI, -19.4 to -3.8) (P = .003). Conclusions and relevance: Telephone-based CBT-I improved sleep in perimenopausal and postmenopausal women with insomnia and hot flashes. Results support further development and testing of centralized CBT-I programs for treating menopausal insomnia. Trial registration: clinicaltrials.gov Identifier: NCT01936441.

JAMA internal medicine · randomised controlled trial · 114 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 →

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 →

Cognitive ability at kindergarten entry and socioeconomic status.

Objective: To examine how gradients in socioeconomic status (SES) impact US children's reading and math ability at kindergarten entry and determine the contributions of family background, health, home learning, parenting, and early education factors to those gradients. Methods: Analysis of 6600 children with cognitive assessments at kindergarten entry from the US Early Childhood Longitudinal Birth Cohort Study. A composite SES measure based on parent's occupation, education, and income was divided into quintiles. Wald F tests assessed bivariate associations between SES and child's cognitive ability and candidate explanatory variables. A decomposition methodology examined mediators of early cognitive gradients. Results: Average reading percentile rankings increased from 34 to 67 across SES quintiles and math from 33 to 70. Children in lower SES quintiles had younger mothers, less frequent parent reading, less home computer use (27%-84%), and fewer books at home (26-114). Parent's supportive interactions, expectations for their child to earn a college degree (57%-96%), and child's preschool attendance (64%-89%) increased across quintiles. Candidate explanatory factors explained just over half the gradients, with family background factors explaining 8% to 13%, health factors 4% to 6%, home learning environment 18%, parenting style/beliefs 14% to 15%, and early education 6% to 7% of the gaps between the lowest versus highest quintiles in reading and math. Conclusions: Steep social gradients in cognitive outcomes at kindergarten are due to many factors. Findings suggest policies targeting levels of socioeconomic inequality and a range of early childhood interventions are needed to address these disparities.

Pediatrics · 65 citationsread the source →

Psychological and Psychosomatic Symptoms of Second Victims of Adverse Events: a Systematic Review and Meta-Analysis.

Objectives: Despite growing interest in the second-victim phenomenon and greater awareness of its consequences, there has not been a meta-analysis quantifying the negative impact of adverse events on providers involved in adverse events. This study systematically reviewed the types and prevalence of psychological and psychosomatic symptoms among second victims. Methods: We conducted a systematic review of nine electronic databases up to February 2017, without restrictions to publication date or language, examining also additional sources (e.g., gray literature, volumes of journals). Two reviewers performed the search, selection process, quality assessment, data extraction, and synthesis. We resolved disagreements by consensus and/or involving a third reviewer. Quantitative studies on the prevalence of psychological and psychosomatic symptoms of second victims were eligible for inclusion. We used random effects modeling to calculate the overall prevalence rates and the I statistic. Results: Of 7210 records retrieved, 98 potentially relevant studies were identified. Full-text evaluation led to a final selection of 18 studies, based on the reports of 11,649 healthcare providers involved in adverse events. The most prevalent symptoms were troubling memories (81%, 95% confidence interval [CI] = 46-95), anxiety/concern (76%, 95% CI = 33-95), anger toward themselves (75%, 95% CI = 59-86), regret/remorse (72%, 95% CI = 62-81), distress (70%, 95% CI = 60-79), fear of future errors (56%, 95% CI = 34-75), embarrassment (52%, 95% CI = 31-72), guilt (51%, 95% CI = 41-62), and sleeping difficulties (35%, 95% CI = 22-51). Conclusions: Second victims report a high prevalence and wide range of psychological symptoms. More than two-thirds of providers reported troubling memories, anxiety, anger, remorse, and distress. Preventive and therapeutic programs should aim to decrease second victims' emotional distress.

Journal of patient safety · meta-analysis · 134 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 →

Interventions Associated With Reduced Loneliness and Social Isolation in Older Adults: A Systematic Review and Meta-analysis.

Importance: Loneliness and social isolation are public health concerns faced by older adults due to physical, cognitive, and psychosocial changes that develop with aging. Loneliness and social isolation are associated with increased morbidity and mortality. Objective: To evaluate interventions, targeting older adults, associated with a reduction in loneliness and social isolation. Data sources: OVID, CINAHL, CENTRAL, Embase, PsychINFO, Web of Science, and Scopus were searched from inception to March 2020. Study selection: Peer-reviewed randomized clinical trials measuring loneliness and social isolation or support in adults aged 65 years or older. Only English language articles were included. Data extraction and synthesis: Two independent reviewers screened studies, extracted data, and assessed risk of bias. Random-effects models were performed to pool the overall effect size by intervention. Statistical heterogeneity was evaluated with the I2 statistic and by estimating prediction intervals. Data were analyzed from November 2021 to September 2022. Main outcomes and measures: Quantitative measures of loneliness, social isolation, or social support based on an effect size of standardized mean differences. Results: Seventy studies were included in the systematic review (8259 participants); 44 studies were included in the loneliness meta-analysis (33 in the community with 3535 participants; 11 in long-term care with 1057 participants), with participants' ages ranging from 55 to 100 years. Study sizes ranged from 8 to 741 participants. Interventions included animal therapy, psychotherapy or cognitive behavioral therapy, multicomponent, counseling, exercise, music therapy, occupational therapy, reminiscence therapy, social interventions, and technological interventions. Most interventions had a small effect size. Animal therapy in long-term care, when accounting for studies with no active controls, had the largest effect size on loneliness reduction (-1.86; 95% CI, -3.14 to -0.59; I2 = 86%) followed by technological interventions (videoconferencing) in long-term care (-1.40; 95% CI, -2.37 to -0.44; I2 = 70%). Conclusions and relevance: In this study, animal therapy and technology in long-term care had large effect sizes, but also high heterogeneity, so the effect size's magnitude should be interpreted with caution. The small number of studies per intervention limits conclusions on sources of heterogeneity. Overall quality of evidence was very low. Future studies should consider measures of social isolation in long-term care and identify the contextual components that are associated with a reduction in loneliness.

JAMA network open · meta-analysis · 137 citationsread the source →

Efficacy of school-based interventions aimed at decreasing sugar-sweetened beverage consumption among adolescents: a systematic review.

Objective: To verify the efficacy of school-based interventions aimed at reducing sugar-sweetened beverage (SSB) consumption among adolescents in order to develop or improve public health interventions. Design: Systematic review of interventions targeting adolescents and/or the school environment. Setting: The following databases were investigated: MEDLINE/PubMed, PsycINFO, CINAHL and EMBASE. Proquest Dissertations and Theses was also investigated for unpublished trials. Subjects: Adolescents were defined as individuals between the ages of 12 and 17 years. Results: A total of thirty-six studies detailing thirty-six different interventions tested among independent samples (n 152 001) were included in the review. Twenty interventions were classified as educational/behavioural and ten were classified as legislative/environmental interventions. Only six interventions targeted both individuals and their environment. Over 70 % of all interventions, regardless of whether they targeted individuals, their environment or both, were effective in decreasing SSB consumption. Legislative/environmental studies had the highest success rate (90·0 %). Educational/behavioural interventions only and interventions that combined educational/behavioural and legislative/environmental approaches were almost equally effective in reducing SSB consumption with success rates of 65·0 and 66·7 %, respectively. Among the interventions that had an educational/behavioural component, 61·5 % were theory-based. The behaviour change techniques most frequently used in interventions were providing information about the health consequences of performing the behaviour (72·2 %), restructuring the physical environment (47·2 %), behavioural goal setting (36·1 %), self-monitoring of behaviour (33·3 %), threat to health (30·6 %) and providing general social support (30·6 %). Conclusions: School-based interventions show promising results to reduce SSB consumption among adolescents. A number of recommendations are made to improve future studies.

Public health nutrition · meta-analysis · 69 citationsread the source →

Probiotics for the prevention of pediatric antibiotic-associated diarrhea.

Background: Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action. Objectives: The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. Search methods: MEDLINE, Embase, CENTRAL, CINAHL, and the Web of Science (inception to 28 May 2018) were searched along with registers including the ISRCTN and Clinicaltrials.gov. We also searched the NICE Evidence Services database as well as reference lists from relevant articles. Selection criteria: Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. Data collection and analysis: Study selection, data extraction, and risk of bias assessment were conducted independently by two authors. Dichotomous data (incidence of AAD, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea) as mean difference (MD), along with corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For studies reporting on microbiome characteristics using heterogeneous outcomes, we describe the results narratively. The certainty of the evidence was evaluated using GRADE. Main results: Thirty-three studies (6352 participants) were included. Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. The risk of bias was determined to be high in 20 studies and low in 13 studies. Complete case (patients who did not complete the studies were not included in the analysis) results from 33 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control. After 5 days to 12 weeks of follow-up, the incidence of AAD in the probiotic group was 8% (259/3232) compared to 19% (598/3120) in the control group (RR 0.45, 95% CI 0.36 to 0.56; I² = 57%, 6352 participants; NNTB 9, 95% CI 7 to 13; moderate certainty evidence). Nineteen studies had loss to follow-up ranging from 1% to 46%. After making assumptions for those lost, the observed benefit was still statistically significant using an extreme plausible intention-to-treat (ITT) analysis, wherein the incidence of AAD in the probiotic group was 12% (436/3551) compared to 19% (664/3468) in the control group (7019 participants; RR 0.61; 95% CI 0.49 to 0.77; P <0.00001; I² = 70%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥ 5 billion CFUs per day) is more effective than low probiotic dose (< 5 billion CFUs per day), interaction P value = 0.01. For the high dose studies the incidence of AAD in the probiotic group was 8% (162/2029) compared to 23% (462/2009) in the control group (4038 participants; RR 0.37; 95% CI 0.30 to 0.46; P = 0.06; moderate certainty evidence). For the low dose studies the incidence of AAD in the probiotic group was 8% (97/1155) compared to 13% (133/1059) in the control group (2214 participants; RR 0.68; 95% CI 0.46 to 1.01; P = 0.02). Again, assumptions for loss to follow-up using an extreme plausible ITT analysis was statistically significant. For high dose studies the incidence of AAD in the probiotic group was 13% (278/2218) compared to 23% (503/2207) in control group (4425 participants; RR 0.54; 95% CI 0.42 to 0.70; P <0.00001; I² = 68%; moderate certainty evidence).None of the 24 trials (4415 participants) that reported on adverse events reported any serious adverse events attributable to probiotics. Adverse event rates were low. After 5 days to 4 weeks follow-up, 4% (86/2229) of probiotics participants had an adverse event compared to 6% (121/2186) of control participants (RD 0.00; 95% CI -0.01 to 0.01; P < 0.00001; I² = 75%; low certainty evidence). Common adverse events included rash, nausea, gas, flatulence, abdominal bloating, and constipation. After 10 days to 12 weeks of follow-up, eight studies recorded data on our secondary outcome, the mean duration of diarrhea; with probiotics reducing diarrhea duration by almost one day (MD -0.91; 95% CI -1.38 to -0.44; P <0.00001; low certainty evidence). One study reported on microbiome characteristics, reporting no difference in changes with concurrent antibiotic and probiotic use. Authors' conclusions: The overall evidence suggests a moderate protective effect of probiotics for preventing AAD (NNTB 9, 95% CI 7 to 13). Using five criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate the subgroup effect based on high dose probiotics (≥ 5 billion CFUs per day) was credible. Based on high-dose probiotics, the NNTB to prevent one case of diarrhea is 6 (95% CI 5 to 9). The overall certainty of the evidence for the primary endpoint, incidence of AAD based on high dose probiotics was moderate due to the minor issues with risk of bias and inconsistency related to a diversity of probiotic agents used. Evidence also suggests that probiotics may moderately reduce the duration of diarrhea, a reduction by almost one day. The benefit of high dose probiotics (e.g. Lactobacillus rhamnosus orSaccharomyces boulardii) needs to be confirmed by a large well-designed multi-centered randomized trial. It is premature to draw firm conclusions about the efficacy and safety of 'other' probiotic agents as an adjunct to antibiotics in children. Adverse event rates were low and no serious adverse events were attributable to probiotics. Although no serious adverse events were observed among inpatient and outpatient children, including small studies conducted in the intensive care unit and in the neonatal unit, observational studies not included in this review have reported serious adverse events in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation.

The Cochrane database of systematic reviews · meta-analysis · 162 citationsread the source →

Prevention and Management of Noncommunicable Disease

Morbidity and mortality from preventable, noncommunicable chronic disease (NCD) threatens the health of our populations and our economies. The accumulation of vast amounts of scientific knowledge has done little to change this. New and innovative thinking is essential to foster new creative approaches that leverage and integrate evidence through the support of big data, technology, and design thinking. The purpose of this paper is to summarize the results of a consensus meeting on NCD prevention sponsored by the International Olympic Committee (IOC) in April 2013. Within the context of advocacy for multifaceted systems change, the IOC's focus is to create solutions that gain traction within health care systems. The group of participants attending the meeting achieved consensus on a strategy for the prevention and management of chronic disease that includes the following: Focus on behavioral change as the core component of all clinical programs for the prevention and management of chronic disease. Establish actual centers to design, implement, study, and improve preventive programs for chronic disease. Use human-centered design (HCD) in the creation of prevention programs with an inclination to action, rapid prototyping and multiple iterations. Extend the knowledge and skills of Sports and Exercise Medicine (SEM) professionals to build new programs for the prevention and treatment of chronic disease focused on physical activity, diet, and lifestyle. Mobilize resources and leverage networks to scale and distribute programs of prevention. True innovation lies in the ability to align thinking around these core strategies to ensure successful implementation of NCD prevention and management programs within health care. The IOC and SEM community are in an ideal position to lead this disruptive change. The outcome of the consensus meeting was the creation of the IOC Non-Communicable Diseases ad hoc Working Group charged with the responsibility of moving this agenda forward. INTRODUCTION Noncommunicable diseases (NCD, Table 1) account for 60% of all deaths and 44% of premature deaths.1,2 Noncommunicable chronic diseases are now the greatest cause of morbidity and mortality even in developing countries where they account for twice as many deaths as HIV/AIDS, tuberculosis, malaria, and all other infectious diseases combined.1–3 They are a barrier to achieving the United Nations' (UN) Millennium Development Goals4 and are a global threat to our economies in addition to our health. A report by the World Economic Forum and Harvard University estimates that chronic disease, currently costing 2% of the global gross domestic product (GDP), will cost the global economy 30 trillion USD over the next 2 decades, cumulatively 48% of the global GDP in 2010.3 But, chronic diseases are largely preventable. Their main causes are related to lifestyle, that is physical inactivity (recently labeled by The Lancet as being pandemic5), an unhealthy diet, and tobacco and alcohol abuse.TABLE 1: List of Noncommunicable DiseasesIn 2010, the World Health Organization (WHO) and the International Olympic Committee (IOC) signed a memorandum of understanding to jointly promote activities and policy choices designed to reduce the risk of NCD.6 This was followed by a landmark speech given by the IOC President to the plenary session of the Sixty-Sixth General Assembly of the United Nations, September 19, 2011; a “watershed event” to “replace ignorance and inertia with awareness and right actions”.7 IOC President Dr. Jacques Rogge told the Assembly: “The problem is acute, the solution is at hand. It is a grim picture, except for one thing: We can do something about it.” Low cost, highly effective solutions for the prevention and management of NCD are available.5 The IOC President emphasized the WHO recommendations on physical activity as core to NCD prevention.6 He called for safe and accessible public spaces for physical activity and sport, partnerships with transportation and urban planning, increased physical education, and better sport infrastructure and organization, thus building on the comprehensive, broad-based, long-term approaches recommended by International Society for Physical Activity and Health (ISPAH), the Grand Challenges Global Partnership, the WHO, the European Commission (EC), the World Economic Forum (WEF), Active Canada, Exercise is Medicine, the Organization for Economic Co-operation and Development (OECD),1–3,8–13 and many others. To date, efforts to promote a “home” for prevention within health care has largely failed. Waiting for comprehensive, emergent reform of dysfunctional health care systems is unrealistic. Likewise, results from reductionist research studies have not been successfully implemented and scaled in such a way as to create population-wide impact. The current approaches to chronic disease prevention and management involving public health and global health strategy14 may need to be merged with HCD. The latter approach, used as a catalyst for change in other industries, focuses on the importance of the human element in behavioral change.7 Successful implementation of testable, novel approaches will require committed, visionary leadership willing to reframe the problem from a practical, human-design perspective while sticking to a clear strategy to mobilize the resources and capacities needed for change. The objective of this IOC consensus meeting was to achieve alignment on a strategy to design a sustainable plan of action for the prevention and management of NCD, coupling existing scientific evidence with HCD, focusing particularly on physical activity/exercise and behavioral change. In order to accomplish this objective, the SEM community must overcome considerable inertia created by the complexity and magnitude of the NCD problem and its context. The SEM community must bundle its efforts and embrace a new, creative approach aligned with a strategy that is clear, concrete, and human-centered. THE PROBLEM For most of human history, people needed to be physically active to survive. Today, for instance, only 20% of Norwegian,15 8.2% of US,16 and 5% of UK17 adults meet physical activity guidelines. Over a 4-decade period, physical activity in the US has declined 32% and is projected to decline even further to 46% by 2030,18 while from 1991 to 2009, China's physical activity rates dropped by 45%.18 In the Arab World, 8 countries have physical inactivity levels ranging from 33% to 70% of the population.19 Over the past 50 years there has been a marked decline in energy expenditure for household management20 and civilian occupation,21 sufficient to explain the rising prevalence of obesity.22 Worldwide, physical inactivity and smoking are responsible for more deaths than any other modifiable risk factors.5 Clinical scientists are continuing to identify more characteristics that magnify the problem. For example, sitting time has been shown to be associated with increased cardio-metabolic risk independent of levels of physical activity.23–25 Low aerobic fitness is a risk factor for all-cause mortality, cancer, and cardiovascular disease, independent of body fatness.26,27 While the problem of physical inactivity, poor diet, and unhealthy lifestyle behaviors is evident and clear, the real problem is that we have not been able to mitigate the steady rise in NCD. In fact, the morbidity and mortality from NCD has worsened during the time we have been accumulating research data and publishing position statements and recommendations.28 The mere existence of national physical activity policies or action plans does not ensure or Physical activity are not implementation and implementation does not We can that urban of education, global health care and health community sport the health care and transportation do The SEM community can do its lies to the of physical activity, diet, and health. global advocacy for a of systems the and of NCD and to the and complexity The health care for policies to change and the the health care to programs of prevention. The to the of by in New is an of the of even with policy In the of the of Health and there is for the health care to an of the that real change the to in the with policy health care to change and and that alignment and prevention in the of and and the vast of scientific while has been for there is clear plan to We the the complexity of chronic disease and the reductionist approach being used to as as the that from The of health does not for by focusing on a We must on the one position statements and recommendations that and and that responsibility to on the other a approach by and scientific that knowledge and that does not We must to around the that from in prevention. the approach to thinking within has the approach to health care the of and the the of and for health care the of a to and the of human In order to create a consensus action plan for the prevention and management of chronic disease, the IOC a group of April in sport and public clinical design and of education, technology, and lifestyle to participants for in New in to plan a design thinking approach to the The 2 meeting with an and of the problem followed by and by the the to this meeting are do is the most that to to reduce the morbidity and mortality associated with chronic and to that in the next to existing of evidence as as to new of and the group to the for the for behavioral change, the importance of HCD, the of the SEM of and the for actual centers within to prevention and the importance of the IOC's the meeting time was a design thinking approach to integrate scientific evidence with human to achieve consensus for an action The was a of the and an action the of unhealthy on the chronic disease to lifestyle and to the of national health policies and For this a focus on behavioral change as the core component of all clinical programs for the prevention and management of chronic disease is and human is given the and of and and and and policy and In a study, of responsibility for the health care to This complexity the as to or for physical inactivity and other lifestyle The of can be on or more of physical inactivity and other lifestyle related is to the is the by physical activity our such as the and support people through change a that in a and In can be used to change the a for by at a more and in the through for strategies to build a efforts to multiple policy and to about that the of and as of for of and of account the importance of the and the of that people lifestyle in many such are or of most are designed from a perspective the as the of are more to and solutions need to with the of people The of in for NCD prevention. are to through of in the of these In order to change these one to account that a will action and ability to the are to in a physical or For example, even an highly to a or will most not the physical ability cardiovascular and to be over the of the to be and the ability to with of physical activity that can be increased as one and the of the at and the of more a more and change is than a such as a successful of one in there may be a to many other of the one with a change may or by change in that a the of a preventive is the of the health outcome of the the health in health This the the and of can be and and be A is related to the of data that by and to and care by education, and care to at levels of are such as or that may in to about physical activity as a support to behaviors through and the from data is to in the more The of big data by the has a management in other in and in to For example, of and to better and product on of the In is able to the of an more and than the systems of the US for data have been used in such as and to and the In health data the of to largely of health care for will leverage foster behavioral change and lead to by the or a for a successful prevention In preventive health care we from our knowledge of a to and This for many of our for its with lifestyle change. For example, we do not to and recommendations an do we with the knowledge and skills to and to our a perspective we the of with to and In fact, health care and more or about the importance of physical activity to and of the with is poor and from the and the are actual where scientific and are to and prevention While of the to be the shown the approach with the of the of is as as physical and behavioral This the health care in and understanding the context of the current and for behavioral change. and these and the of that can be used to on characteristics that to the of for the and with the health care can the in an to that in behavioral change are used as for that build and The of is and by includes of in addition to and within an that includes health care fitness and health and This and is to with existing in order to the with an and is for The ideal for and of these programs is in research centers that meet for and The of such programs will over time with the of data such that the will a more way of behavioral change achieving the will more and will be to achieve scale for example, to other health care or fitness designed from a perspective that only the as the of the product or by people a approach, for implementation and at the and are not are given solutions that only focus on the treatment of diseases of solutions that of For example, a is one treatment for many a behavioral plan for may the of this treatment prevention the context for behavioral change the right is most to than the The of active human in understanding and developing solutions may explain of we have not achieved results with 1: is a for innovation that people in order to there are is is or within the is the the innovation will of a sustainable to to people and for people human innovation and an approach will and even of is the of HCD. The the we from to solutions understanding and through and to identify and is to the right to the way a problem is the approach to approaches are used to for and prototyping for from care that is of and to and and that all clinical has been as a there is an as that on understanding and in order to design solutions that meet from treatment from a behavioral perspective health are from is as the of an outcome of a solutions in prevention. The for health one that has not been is to responsibility for understanding the that behavioral change within this context. design to solutions from the human perspective 1) and and in and solutions to context and design and to the context of and to behavioral change and and with people are used to the context of they and need in and they or about the way or are and human element is to gain on to the problem from the perspective in a way that can to the sustainable A design problem to is the real problem being and we overcome The solutions are created with human in and focus on the and of For example, an increased to and and of in can be to the and of the design is an approach that can other such as and that for the that require these in a and the at the of is that with the is is an as health care professionals increased in focusing on and that can have a on The of creative and thinking with and has been successful in and design with its inclination to action, rapid and multiple can be and for its ability to create effective preventive programs for chronic disease. The of SEM has its in the scientific of human and the to physical activity and that in multiple systems. The human body has to in to in and and as as in and in in aerobic and as as and are The to be used to these in the while is most used for For an or one with chronic disease and multiple in the way is in The that results in these is the associated with health this for a clinical than its to health and of has not been For this is to the knowledge and skills of SEM to the to build new programs for the prevention and management of chronic disease focused on physical activity, diet, and other lifestyle chronic disease and most people multiple chronic For this a of health disease is not The more approach is the of chronic disease and to and over the of chronic disease are a that many years during preventive may the and of the the of as health and the of disease as an treatment or to identify risk these and the of of chronic disease. prevention can the of existing chronic disease on and the of related chronic diseases is an as to to successfully the prevention and management of chronic disease in the clinical of SEM and care The is one of new clinical and in chronic disease prevention and management to new preventive to the public in an effective and The focus of most SEM and is on the care of of the of the of SEM is other is not or disease To date, knowledge and clinical skills in the of chronic disease prevention and management have not been the focus of continuing in even this be a and to clinical in chronic disease prevention and management must be and for SEM and care that includes and health care and the fitness and there is “home” for prevention within health care. are prevention centers that can be by to or improve health. existing and lifestyle in there are programs of population-wide scale that focus on behavioral change with to physical activity, or other lifestyle This is being by and fitness and a on that from that the health care This results in a of and the health care to these as the and to on prevention. To actual centers to design, implement, study, and improve preventive programs for chronic disease, the by to be with the by the and with approach and The creation of a sustainable for prevention physical centers these be centers that meet for the of evidence with human-centered design, the of technology, and the inclination to action and rapid of these with with health and can as While there are a of studies of behavioral change the current clinical approach to be an on the and skills of and health The centers the for an ideal prevention by the of behavioral design through and The factor that will and the ability to meet the human that are currently is as more of disease with and human the of the programs are around the for the the disease. an to and behavioral with the The and prevention for health care and with and such as these have little to a prevention they are of reductionist thinking related to the or of disease or risk programs around such of other the human that the of prevention and thinking in disease any prevention its and to the and of a disease. Likewise, can be not to prevention management of chronic disease. It is clear that prevention to disease or risk and management to with chronic disease. But, this is and as an to behavioral change with or the or of disease or risk most to people is that the is is the In the real of is essential to identify and characteristics of This to from people on of disease and is the of prevention. of health care is for with of health care to with largely health care and the This is a of our in are disease. While prevention from a we must the of of prevention and this focuses the of on the reductionist of and of disease. lifestyle programs with to the of behavioral design of a is or they are clinical to this by focusing on one prevention only of population-wide impact. For this we need to from of prevention to concrete, programs for of in to and This approach, that human for and is a factor for the of prevention on this is The of a prevention physical design and and and of the must be on evidence and current and by health care professionals with and of this to be includes all the that with the physical ability to a given is a of that such as the for to and of the of a prevention In these and to a of account the from of programs can be better designed to that human for and is a factor for the of prevention programs these results and a can be designed and to meet the for data physical activity that can in at the and at the to support The in programs of prevention will a and that can to identify and at the in of for This the currently of behavioral change by health care professionals and prevention a and approach of a programs of and cost be scaled at the the core of the of prevention and programs and centers is the creation of for and through Likewise, a is in order to scale programs and population-wide A the global SEM and care sport and Olympic can mobilize resources and leverage networks to scale and distribute prevention programs Working within these and the greatest for innovation in prevention. in chronic disease prevention and management will require a to be and a focus on rapid will require a approach with strategy and to and and resources to create and have an to in the prevention and management of noncommunicable and the IOC is the in this the International and the can an in physical activity through sport by with the WHO, International Physical Activity SEM and countries now focus on a of the health of the by physical activity as of such as the Olympic and The IOC has its leadership in the of programs such as for Olympic IOC Commission such as health and fitness for people through physical activity and and and the Olympic and through its with the and the The Olympic and the Olympic are on a and that sport and with people of all and from around the Olympic people to be the they can in partnerships build on this in build responsible and within and are in a with the as a is a to promote an prevention through an with and and and in order to and a The and through the SEM and care developing successful and prevention programs with these programs can be scaled to lead to change prevention. The as a will its and with the SEM community by and its the prevention of chronic disease, a for change of the by of the IOC's activities will new and innovative design will require and for creative while will foster and the for for essential for the given its to for a multifaceted and to with policy and is for the IOC to focus on in the to the that to all public health at is for the to as can an only one at a The IOC will with the SEM community on the of clinical lifestyle for health care professionals to and in change. the and resources within the IOC and the of the SEM the of this focused on the has the to be The creation of prevention centers the leadership to clear a and of from within health care that will have population-wide impact. centers will evidence while design thinking current health In order to gain support and to that are currently as behavioral with an inclination to rapid prototyping are This will and action in is to identify a core group of and with and to and to prototyping and is to in the clinical of a its on its and is to successfully such programs to the and the fitness This can through and to health care professionals in order to create a of prevention centers and are for the of professionals in the of disease prevention and there is group of health care professionals that the of knowledge and skills for clinical in disease are fitness physical and other of the of and and within these is The has the ability to in prevention and the new approach to resources be and and For example, the IOC has a in and a further the prevention a of prevention centers The is to education, and to essential of that the of prevention within the health care This will further for a to prevention even within health care The of lifestyle physical activity in the of and other health will be more and an prevention are at hand. The IOC Working Group on NCD to a for change that evidence and innovation through HCD. While long-term that require and and the IOC will an active with a focused on to current health care with reductionist can only to the that a disruptive approach is needed we are to be successful in the of chronic disease. The are not of more research and scientific sufficient or health care The is one of on the one and plans on the in the of an problem and to change. solutions are with human-centered programs to preventive is the

Clinical Journal of Sport Medicine · 22 citationsread the source →

Exercise as adjunctive therapy for systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is a rare, chronic autoimmune inflammatory disease with a prevalence varying from 4.3 to 150 people in 100,000, or approximately five million people worldwide. Systemic manifestations frequently include internal organ involvement, a characteristic malar rash on the face, pain in joints and muscles, and profound fatigue. Exercise is purported to be beneficial for people with SLE. For this review, we focused on studies that examined all types of structured exercise as an adjunctive therapy in the management of SLE. Objectives: To evaluate the benefits and harms of structured exercise as adjunctive therapy for adults with SLE compared with usual pharmacological care, usual pharmacological care plus placebo and usual pharmacological care plus non-pharmacological care. Search methods: We used standard, extensive Cochrane search methods. The latest search date was 30 March 2022. Selection criteria: We included randomised controlled trials (RCTs) of exercise as an adjunct to usual pharmacological treatment in SLE compared with placebo, usual pharmacological care alone and another non-pharmacological treatment. Major outcomes were fatigue, functional capacity, disease activity, quality of life, pain, serious adverse events, and withdrawals due to any reason, including any adverse events. Data collection and analysis: We used standard Cochrane methods. Our major outcomes were 1. fatigue, 2. functional capacity, 3. disease activity, 4. quality of life, 5. pain, 6. serious adverse events, and 7. withdrawals due to any reason. Our minor outcomes were 8. responder rate, 9. aerobic fitness, 10. depression, and 11. anxiety. We used GRADE to assess certainty of evidence. The primary comparison was exercise compared with placebo. Main results: We included 13 studies (540 participants) in this review. Studies compared exercise as an adjunct to usual pharmacological care (antimalarials, immunosuppressants, and oral glucocorticoids) with usual pharmacological care plus placebo (one study); usual pharmacological care (six studies); and another non-pharmacological treatment such as relaxation therapy (seven studies). Most studies had selection bias, and all studies had performance and detection bias. We downgraded the evidence for all comparisons because of a high risk of bias and imprecision. Exercise plus usual pharmacological care versus placebo plus usual pharmacological care Evidence from a single small study (17 participants) that compared whole body vibration exercise to whole body placebo vibration exercise (vibrations switched off) indicated that exercise may have little to no effect on fatigue, functional capacity, and pain (low-certainty evidence). We are uncertain whether exercise results in fewer or more withdrawals (very low-certainty evidence). The study did not report disease activity, quality of life, and serious adverse events. The study measured fatigue using the self-reported Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue), scale 0 to 52; lower score means less fatigue. People who did not exercise rated their fatigue at 38 points and those who did exercise rated their fatigue at 33 points (mean difference (MD) 5 points lower, 95% confidence interval (CI) 13.29 lower to 3.29 higher). The study measured functional capacity using the self-reported 36-item Short Form health questionnaire (SF-36) Physical Function domain, scale 0 to 100; higher score means better function. People who did not exercise rated their functional capacity at 70 points and those who did exercise rated their functional capacity at 67.5 points (MD 2.5 points lower, 95% CI 23.78 lower to 18.78 higher). The study measured pain using the SF-36 Pain domain, scale 0 to 100; lower scores mean less pain. People who did not exercise rated their pain at 43 points and those who did exercise rated their pain at 34 points (MD 9 points lower, 95% CI 28.88 lower to 10.88 higher). More participants from the exercise group (3/11, 27%) withdrew from the study than the placebo group (1/10, 10%) (risk ratio (RR) 2.73, 95% CI 0.34 to 22.16). Exercise plus usual pharmacological care versus usual pharmacological care alone The addition of exercise to usual pharmacological care may have little to no effect on fatigue, functional capacity, and disease activity (low-certainty evidence). We are uncertain whether the addition of exercise improves pain (very low-certainty evidence), or results in fewer or more withdrawals (very low-certainty evidence). Serious adverse events and quality of life were not reported. Exercise plus usual care versus another non-pharmacological intervention such as receiving information about the disease or relaxation therapy Compared with education or relaxation therapy, exercise may reduce fatigue slightly (low-certainty evidence), may improve functional capacity (low-certainty evidence), probably results in little to no difference in disease activity (moderate-certainty evidence), and may result in little to no difference in pain (low-certainty evidence). We are uncertain whether exercise results in fewer or more withdrawals (very low-certainty evidence). Quality of life and serious adverse events were not reported. Authors' conclusions: Due to low- to very low-certainty evidence, we are not confident on the benefits of exercise on fatigue, functional capacity, disease activity, and pain, compared with placebo, usual care, or advice and relaxation therapy. Harms data were not well reported.

The Cochrane database of systematic reviews · systematic review · 11 citationsread the source →

Adverse childhood experiences and psychosocial well-being of women who were in foster care as children.

Background and objective: Research has shown that many children in foster care later have psychosocial problems as adults; this is often attributed to cumulative adversities and a lack of supportive caregivers. The risk factors associated with foster care, such as maternal separation and multiple placements, often counteract many protective factors that can ameliorate the effects of childhood adversities. This study assessed the relationship between adverse childhood experiences (ACEs) and psychosocial well-being in women who were in foster care as children. Methods: A total of 101 women aged 18-71 years (mean, 36.83 [12.95] years) completed an anonymous online survey based on the 10-item ACE Questionnaire, the Sense of Coherence questionnaire, and the General Health Questionnaire. Results: More than 56% of respondents were identified as experiencing current psychological distress. Sense of coherence scores (mean, 54.26 [15.35]) showed a significant inverse association with both General Health Questionnaire (mean, 14.83 [5.88]) and ACE (mean, 5.68 [2.90]) scores (r = -0.64 and -0.31, respectively) and 97% reported at least 1 ACE, 70% reported ≥ 5 and 33% reported ≥ 8. Linear regressions indicated that ACEs reported to occur before foster care were associated with lower levels of sense of coherence (8%) and higher levels of psychological distress (6%). Physical neglect and living in a dysfunctional household (parental loss, maternal abuse, or household member associated with substance abuse or prison) significantly decreased during foster care by 16 and 19 percentage points, respectively. Rates of emotional and physical abuse did not change. Conclusion: The number of ACEs was associated with the level of psychological distress. Our findings suggest that children entering the foster care system are already vulnerable and at risk of experiencing ACEs during foster care and psychological distress during adulthood. Measures implemented to protect children must not cause more harm than good. Social services that preserve and strengthen the family unit and reduce the number of ACEs both before and during foster care are recommended. Social workers and clinicians who are trained to address and manage the unique developmental needs of children in foster care may help reduce the effects of ACEs and optimize developmental health.

The Permanente journal · 64 citationsread the source →

Effectiveness of Family Integrated Care in neonatal intensive care units on infant and parent outcomes: a multicentre, multinational, cluster-randomised controlled trial.

Background: Despite evidence suggesting that parent involvement was beneficial for infant and parent outcomes, the Family Integrated Care (FICare) programme was one of the first pragmatic approaches to enable parents to become primary caregivers in the neonatal intensive care unit (NICU). We aimed to analyse the effect of FICare on infant and parent outcomes, safety, and resource use. Methods: In this multicentre, cluster-randomised controlled trial, we stratified 26 tertiary NICUs from Canada, Australia, and New Zealand by country and size, and assigned them, using a computer-generated random allocation sequence, to provide FICare or standard NICU care. Eligible infants were born at 33 weeks' gestation or earlier, and had no or low-level respiratory support; parents gave written informed consent for enrolment. To be eligible, parents in the FICare group had to commit to be present for at least 6 h a day, attend educational sessions, and actively care for their infant. The primary outcome, analysed at the individual level, was infant weight gain at day 21 after enrolment. Secondary outcomes were weight gain velocity, high frequency breastfeeding (≥6 times a day) at hospital discharge, parental stress and anxiety at enrolment and day 21, NICU mortality and major neonatal morbidities, safety, and resource use (including duration of oxygen therapy and hospital stay). This trial is registered with ClinicalTrials.gov, number NCT01852695. Findings: From Oct 1, 2012, 26 sites were randomly assigned to provide FICare (n=14) or standard care (n=12). One site assigned to FICare discontinued because of poor site enrolment. Parents and infants were enrolled between April 1, 2013, and Aug 31, 2015, with 895 infants being eligible in the FICare group and 891 in the standard care group. At day 21, weight gain was greater in the FICare group than in the standard care group (mean change in Z scores -0·071 [SD 0·42] vs -0·155 [0·42]; p<0·0002). Average daily weight gain was significantly higher in infants receiving FICare than those receiving standard care (mean daily weight gain 26·7 g [SD 9·4] vs 24·8 g [9·5]; p<0·0001). The high-frequency exclusive breastmilk feeding rate at discharge was higher for infants in the FICare group (279 [70%] of 396) than those in the standard care group (394 [63%] of 624; p=0·016). At day 21, parents in the FICare group had lower mean stress scores than did parents in the standard care group (2·3 [SD 0·8] vs 2·5 [0·8]; p<0·00043), and lower mean anxiety scores (70·8 [20·1] vs 74·2 [19·9]; p=0·0045). There were no significant differences between groups in the rates of the secondary outcomes of mortality, major morbidity, duration of oxygen therapy, and duration of hospital stay. Although the safety assessment was not completed, there were no adverse events. Interpretation: FICare improved infant weight gain, decreased parent stress and anxiety, and increased high-frequency exclusive breastmilk feeding at discharge, which together suggest that FICare is an important advancement in neonatal care. Further research is required to examine if these results translate into better long-term outcomes for families. Funding: Canadian Institutes of Health Research Partnerships for Health System Improvement, and Ontario Ministry of Health and Long-Term Care.

The Lancet. Child & adolescent health · randomised controlled trial · 374 citationsread the source →

Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.

Background: No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. Methods: The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685). Findings: 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (-0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (-0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. Interpretation: The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. Funding: French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.

The Lancet. Neurology · randomised controlled trial · 632 citationsread the source →

A three arm cluster randomised controlled trial to test the effectiveness and cost-effectiveness of the SMART Work & Life intervention for reducing daily sitting time in office workers: study protocol.

Background: Office-based workers typically spend 70-85% of working hours, and a large proportion of leisure time, sitting. High levels of sitting have been linked to poor health. There is a need for fully powered randomised controlled trials (RCTs) with long-term follow-up to test the effectiveness of interventions to reduce sitting. This paper describes the methodology of a three-arm cluster RCT designed to determine the effectiveness and cost-effectiveness of the SMART Work & Life intervention, delivered with and without a height-adjustable desk, for reducing daily sitting. Methods/design: A three-arm cluster RCT of 33 clusters (660 council workers) will be conducted in three areas in England (Leicester; Manchester; Liverpool). Office groups (clusters) will be randomised to the SMART Work & Life intervention delivered with (group 1) or without (group 2) a height-adjustable desk or a control group (group 3). SMART Work & Life includes organisational (e.g., management buy-in, provision/support for standing meetings), environmental (e.g., relocating waste bins, printers), and group/individual (education, action planning, goal setting, addressing barriers, coaching, self-monitoring, social support) level behaviour change strategies, with strategies driven by workplace champions. Baseline, 3, 12 and 24 month measures will be taken. Primary outcome: Objectively measured daily sitting time (activPAL3). Secondary outcomes: objectively measured sitting, standing, stepping, prolonged sitting and moderate-to-vigorous physical activity time and number of steps at work and daily; objectively measured sleep (wrist accelerometry). Adiposity, blood pressure, fasting glucose, glycated haemoglobin, cholesterol (total, HDL, LDL) and triglycerides will be assessed from capillary blood samples. Questionnaires will examine dietary intake, fatigue, musculoskeletal issues, job performance and satisfaction, work engagement, occupational and general fatigue, stress, presenteeism, anxiety and depression and sickness absence (organisational records). Quality of life and resources used (e.g. GP visits, outpatient attendances) will also be assessed. We will conduct a full process evaluation and cost-effectiveness analysis. Discussion: The results of this RCT will 1) help to understand how effective an important simple, yet relatively expensive environmental change is for reducing sitting, 2) provide evidence on changing behaviour across all waking hours, and 3) provide evidence for policy guidelines around population and workplace health and well-being. Trial registration: ISRCTN11618007 . Registered on 21 January 2018.

BMC public health · randomised controlled trial · 25 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 →

Attachment and quality of life in patients with inflammatory bowel disease.

Purpose: Inflammatory bowel diseases (IBD) are chronic disorders affecting psychological well-being, quality of life (QOL), social interactions, and close interpersonal relationships of patients affected. The attachment theory provides a theoretical framework to evaluate the quality of close interpersonal relationships in the context of chronic disorders. The aims of this study were to compare the attachment dimensions between IBD patients and healthy controls and to evaluate the impact of these dimensions on QOL in IBD patients. Methods: One hundred three consecutive IBD outpatients (70 with Crohn's disease and 33 with ulcerative colitis) were recruited in the IBD Unit of the University of Bologna. They were clinically evaluated and filled out the questionnaire Short Form health survey-36 (SF-36), assessing QOL, and the attachment style questionnaire (ASQ), assessing attachment dimensions. One hundred three matched healthy subjects filled out the same questionnaires and represented the control group. Results: IBD patients exhibited worst scores in the QOL measures (both physical and mental health) and in the attachment dimensions Relationships as secondary and Preoccupation with relationships. In IBD, the significant predictors of physical health were disease activity and disease type, while the significant predictors of mental health were disease activity and type, surgery, and the attachment dimensions Confidence and Preoccupation with relationships. Conclusions: Compared to controls, in IBD patients, the close interpersonal relationships are characterized by attachment insecurity that, in turn, is a significant predictor of QOL. These findings suggest plausible insights for psychological interventions in IBD patients with deterioration in QOL.

International journal of colorectal disease · 32 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 →

Study protocol comparing the ethical, psychological and socio-economic impact of personalised breast cancer screening to that of standard screening in the "My Personal Breast Screening" (MyPeBS) randomised clinical trial.

Background: The MyPeBS study is an ongoing randomised controlled trial testing whether a risk-stratified breast cancer screening strategy is non-inferior, or eventually superior, to standard age-based screening at reducing incidence of stage 2 or more cancers. This large European Commission-funded initiative aims to include 85,000 women aged 40 to 70 years, without prior breast cancer and not previously identified at high risk in six countries (Belgium, France, Italy, Israel, Spain, UK). A specific work package within MyPeBS examines psychological, socio-economic and ethical aspects of this new screening strategy. It compares women's reported data and outcomes in both trial arms on the following issues: general anxiety, cancer-related worry, understanding of breast cancer screening strategy and information-seeking behaviour, socio-demographic and economic characteristics, quality of life, risk perception, intention to change health-related behaviours, satisfaction with the trial. Methods: At inclusion, 3-months, 1-year and 4-years, each woman participating in MyPeBS is asked to fill online questionnaires. Descriptive statistics, bivariate analyses, subgroup comparisons and analysis of variations over time will be performed with appropriate tests to assess differences between arms. Multivariate regression models will allow modelling of different patient reported data and outcomes such as comprehension of the information provided, general anxiety or cancer worry, and information seeking behaviour. In addition, a qualitative study (48 semi-structured interviews conducted in France and in the UK with women randomised in the risk-stratified arm), will help further understand participants' acceptability and comprehension of the trial, and their experience of risk assessment. Discussion: Beyond the scientific and medical objectives of this clinical study, it is critical to acknowledge the consequences of such a paradigm shift for women. Indeed, introducing a risk-based screening relying on individual biological differences also implies addressing non-biological differences (e.g. social status or health literacy) from an ethical perspective, to ensure equal access to healthcare. The results of the present study will facilitate making recommendations on implementation at the end of the trial to accompany any potential change in screening strategy. Trial registration: Study sponsor: UNICANCER. My personalised breast screening (MyPeBS). Clinicaltrials: gov (2018) available at: https://clinicaltrials.gov/ct2/show/NCT03672331 Contact: Cécile VISSAC SABATIER, PhD, + 33 (0)1 73 79 77 58 ext + 330,142,114,293, contact@mypebs.eu.

BMC cancer · clinical 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 →

A first national survey of knowledge, attitudes and behaviours towards schizophrenia, bipolar disorders and autism in France.

Background: In order to support evidence-based policies for reduction of stigma, a better understanding of its components: ignorance (knowledge), prejudice (attitude) and discrimination (behaviour) is necessary. This study explores public perceptions and quantifies stigma for three chronic mental disorders: autism, schizophrenia and bipolar disorders in France. Methods: Survey of 1000 adults selected from an established market research panel. The 21-item questionnaire explored knowledge, attitudes and behaviours toward each disorder. Results: Although 95% respondents recognized the names of each disorder fewer than 70% could report specific characteristics and only 33% considered that publically available information was adequate; most respondents identified the media as their main resource. Labeling of conditions in a negative way was frequent (61%) when referring to mental disorders in general, but fell significantly (18%) when linked to an individual with a disorder. Individuals with schizophrenia are assumed to be dangerous; 65% respondents would engage in social distancing from such an individual, versus 29% for bipolar disorders and 7% for autism (p < 0.001). In contrast to other disorders, discrimination against schizophrenia was only partly attenuated in those with familiarity with mental disorders (through personal or family illness). Conclusion: This first population-based survey in France shows that attitudes towards bipolar disorders and autism are less prejudicial than towards schizophrenia. However, most public attitudes and behaviours towards different disorders appear to be based on assumptions rather than knowledge or evidence suggesting a generic information or anti-stigma programme is unlikely to be effective.

BMC psychiatry · 79 citationsread the source →

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 →

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

Medicine · review · 878 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 →

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 →

Suicide in children and young people in England: a consecutive case series.

Background: There is concern about the mental health of children and young people and a possible rise in suicidal behaviour in this group. We have done a comprehensive national multi-agency study of suicide in under 20s in England. We aimed to establish how frequently suicide is preceded by child-specific and young person-specific suicide risk factors, as well as all-age factors, and to identify contact with health-care and social-care services and justice agencies. Methods: This study is a descriptive examination of suicide in a national consecutive sample of children and young people younger than 20 years who died by suicide in England between Jan 1, 2014, and April 30, 2015. We obtained general population mortality data from the Office for National Statistics (ONS). We collected information about antecedents considered to be relevant to suicide (eg, abuse, bullying, bereavement, academic pressures, self-harm, and physical health) from a range of investigations and inquiries, including coroner inquest hearings, child death investigations, criminal justice system reports, and the National Health Service, including data on people in contact with mental health services in the 12 months before their death. Findings: 145 suicides in people younger than 20 years were notified to us during the study period, of which we were able to obtain report data about antecedents for 130 (90%). The number of suicides rose sharply during the late teens with 79 deaths by suicide in people aged 18-19 years compared with 66 in people younger than 18 years. 102 (70%) deaths were in males. 92 (63%) deaths were by hanging. Various antecedents were reported among the individuals for whom we had report data, including academic (especially exam) pressures (35 [27%] individuals), bullying (28 [22%]), bereavement (36 [28%]), suicide in family or friends (17 [13%]), physical health conditions (47 [36%]), family problems (44 [34%]), social isolation or withdrawal (33 [25%]), child abuse or neglect (20 [15%]), excessive drinking (34 [26%]), and illicit drug use (38 [29%]). Suicide-related internet use was recorded in 30 (23%) cases. In the week before death 13 (10%) individuals had self-harmed and 35 (27%) had expressed suicidal ideas. 56 (43%) individuals had no known contact with health-care and social-care services or justice agencies. Interpretation: Improved services for self-harm and mental health are crucial to suicide prevention, but the wide range of antecedents emphasises the roles of schools, primary care, social services, and the youth justice system. Funding: The Healthcare Quality Improvement Partnership.

The lancet. Psychiatry · 71 citationsread the source →

Go Where the Students Are: A Comparison of the Use of Social Networking Sites Between Medical Students and Medical Educators.

Background: Medical education has grown beyond the boundaries of the classroom, and social media is seen as the bridge between informal and formal learning as it keeps students highly engaged with educational content outside the classroom. Objective: The purpose of this study is to explore the perceptions of medical educators and medical students regarding the use of social media for educational purposes. Methods: Both groups (medical educators and students) were invited to take a survey. The surveys consisted of 29 questions, including Likert-style, multiple choice, yes/no, ranking, and short answer questions. The survey forms and statistics were built using Google Drive analytics with the free Spanning Stats module. To compare between professors and students, results were exported to a Microsoft Office Excel spreadsheet (Microsoft Corp, Redmond, WA). The study protocol was approved by The Ottawa Health Science Network Research Ethics Board (OHSN-REB:20140680-01H). Results: The overall response rate to the survey was 40.9% (63/154) for students, and 36% (72/200) for medical educators. The majority of educators (79%, 57/72) and students (100.0%, 63/63) had presence on social networking sites (SNSs). Only (33% 19/57) of educators used SNSs with their students, the most used sites were Facebook (52%, 10/19) and Twitter (47%, 9/19), followed by LinkedIn (21%, 4/19), Google+ (16%, 3/19),YouTube (11%, 2/19), and blogs (11%, 2/19). Facebook (100%, 63/63), YouTube (43%, 27/63), Twitter (31%, 20/63), and Instagram (30%, 19/63) were the sites most commonly used by students. The educators used SNSs mainly to post opinions (86%, 49/57), share videos (81%, 46/57), chat (71%, 41/57), engage in medical education (68%, 40/57), take surveys (24%, 14/57), and play games (5%, 3/57). On the other hand, students used SNSs mainly to chat with friends (94%, 59/63), for medical education purposes (67%, 42/63), to share videos (62%, 39/63), to post opinions (49%, 31/63), to take surveys (11%, 7/63), and to play games (6%, 4/63). Most educators (67%, 38/57) do not use social media in their education Although most of the educators (89%, 17/19) and students (73%, 46/63) found the use of social media time-effective, that it offered an inviting atmosphere (89%, 17/19 and 70%, 44/63), and that it enhanced the learning experience (95%, 18/19 and 70%, 44/63), both groups stated that they had colleagues who refused to use social media. The detractors' concerns included privacy issues (47%, 18/38), time-wasting (34%, 13/38), distraction (21%, 8/38), and that these media might not be suitable for education (11%, 4/38). When it came to using SNSs with the students, the educators most often used SNSs to post articles (42%, 8/19), explanatory comments (31%, 6/19), and videos (27%, 5/19).While students preferred the following posts : Quizzes (87% 55/63), revision files (82% 52/63) and explanatory comments (29% 21/63). Conclusions: Although social media continue to grow, some educators find that they do not offer suitable modes of learning. However, it is important to acknowledge that there are persistent differences in technology adoption and use along gender, racial, and socioeconomic lines; this is often referred to as the "digital divide". The current study shows that students prefer certain posts like quizzes and revision files, while educators are focused on posting videos, articles, and explanatory comments. Medical educators are encouraged to focus on the students in a way to minimize the gap between learners and educators. It will remain our responsibility as educators to focuson the student, use SNSs at their fullest, and integrate them into traditional Web-based management systems and into existingcurricula to best benefit the students.

JMIR medical education · 49 citationsread the source →

Family and Caregiver Spillover Effects in Cost-Utility Analyses of Alzheimer's Disease Interventions.

Background and objective: Alzheimer's disease or dementia can impose a significant burden on family and other informal caregivers. This study investigated how the inclusion of family/informal caregiver spillover effects in a cost-utility analysis may influence the reported value of Alzheimer's disease/dementia interventions. Methods: We used PubMed to identify Alzheimer's disease or dementia cost-utility analyses published from 1 January, 2000 to 31 March, 2018. We reviewed and abstracted information from each study using a two-reader consensus process. We investigated the frequency and methods in which family/caregiver spillover costs and health effects were incorporated into cost-utility analyses, and examined how their inclusion may influence the reported incremental cost-effectiveness ratios. Results: Of 63 Alzheimer's disease/dementia cost-utility analyses meeting inclusion criteria, 44 (70%) considered at least some family/caregiver spillover costs or health effects. Thirty-two studies incorporated spillover costs only, two incorporated spillover health effects only, and ten incorporated both. The most common approach for accounting for spillover was adding informal caregiving time costs to patient costs (n = 36) and adding informal caregiver quality-adjusted life-years to patient values (n = 7). In a subset of 33 incremental cost-effectiveness ratio pairs from 19 studies, incorporating spillover outcomes made incremental cost-effectiveness ratios more favorable (n = 15; 45%) or kept the intervention cost saving (n = 13; 39%) in most cases. In fewer cases, including spillover increased incremental cost-effectiveness ratios (n = 2; 6%), kept the intervention dominated [more costs/less quality-adjusted life-years] (n = 2; 6%), or changed incremental cost-effectiveness ratio from dominated to less cost/less quality-adjusted life-years (n = 1; 3%). In 11 cases (33%), adding spillover effects into analyses resulted in a lower incremental cost-effectiveness ratio that crossed a common cost-effectiveness threshold, which could have downstream implications for programs or policies that are adopted based on cost-effectiveness analysis results. Discussion: Most Alzheimer's disease/dementia cost-utility analyses incorporated spillover costs, often as caregiver time costs, but considered spillover health impacts less often. In about 85% of the analyses, including Alzheimer's disease/dementia spillover cost or health effects decreased incremental cost-effectiveness ratios or kept the intervention cost saving. The broader value of an Alzheimer's disease/dementia intervention to society may in some cases be underestimated without considering these spillover effects on family and informal caregivers.

PharmacoEconomics · 53 citationsread the source →

Effect of Hope Theory combined with active cycle of breathing techniques on pulmonary rehabilitation among COPD patients: A quasi-experiment study.

Background: Pulmonary rehabilitation plays a positive role in improving exercise tolerance and reducing readmission rates in patients with chronic obstructive pulmonary disease (COPD), while the adherence of pulmonary rehabilitation in COPD patients is still poor. The active cycle of breathing techniques based on the Hope Theory is a method to enhance patients' confidence in overcoming the disease and improve the intrinsic motivation of exercise through symptom improvement such as cough and sputum evacuation ability. Objectives: To investigate the effect of Hope Theory education combined with the active cycle of breathing techniques on pulmonary rehabilitation of COPD patients, including exercise adherence, cough and sputum evacuation ability, hope index and exercise self-efficacy. Methods: The study assigned 70 COPD patients hospitalized into intervention and control groups to receive the active cycle of breathing techniques based on Hope Theory or routine treatment in order of admission. Data for cough and sputum evacuation ability, hope, exercise confidence were collected at baseline and after the program. Exercise adherence was assessed at the end of 1, 4 and 8 week following discharge. Results: The actual number of sample consisted of 65 patients divided into intervention (n = 33) and control (n = 32) groups due to severe complications, explicit refusal, disinterest and loss to follow-up. After two weeks of intervention, exercise adherence of the intervention group were better than those of the control group at the end of 4 and 8 week of discharge (P < 0.05). And there was an improvement in cough and sputum evacuation ability, hope and exercise self-efficacy outcomes in the intervention group, with a statistically significant difference between the two groups (P < 0.05). Conclusion: The active cycle of breathing techniques based on Hope Theory education can improve cough and sputum evacuation ability, hope index, exercise self-efficacy, and exercise adherence of COPD patients.

Applied nursing research : ANR · 3 citationsread the source →

Pathophysiology of the risk factors associated with osteoporosis and their correlation to the T-score value in patients with osteopenia and osteoporosis in the United Arab Emirates

INTRODUCTION Osteoporosis is a bone disorder, characterized by loss of bone strength because of an imbalance between the bone resorption and the mechanisms of bone formation, leading to increased fragility and fractures. Pathophysiological mechanisms underlying this disorder include an inadequate formation response during the remodeling process of bone formation, which is an essential factor in osteoporosis pathogenesis. This inadequacy is due to the activation of large numbers of osteoclasts as a response to initiation of hematopoietic precursor cells with failure of normal interaction with the osteoblastic lineage. This will lead to excessive bone resorption that may result in complete loss of trabecular structure and loss of template for new bone formation. The time required for osteoblastic replacement is longer than the resorption phase of bone remodeling by osteoclasts. Therefore, any increase in bone remodeling will lead to damaged architecture and loss of bone mass.[1] Recently, it has been estimated that more than 200 million people worldwide have osteoporosis. On the basis of a statistics from the International Osteoporosis Foundation in 2017, one in five men and one in three women over the age of 50 years will experience fractures during their lifetime because of osteoporosis. Furthermore, it has been found that an osteoporotic fracture occurs every 3s, with the most common fractures occurring at the hip, spine, and wrist.[23] Osteoporotic fractures may be the first manifestation of the disease, which is why it is called a silent disease. Risk factors of osteoporosis, decreased bone mineral density (BMD), and increased fragility fractures may be modifiable or non-modifiable. Among the modifiable factors are low body mass index (BMI), vitamin D deficiency, low calcium intake, excessive caffeine and alcohol consumption, smoking, sedentary life and low physical activity, endocrine disorders (such as estrogen deficiency and insulin-dependent diabetes mellitus or hyperparathyroidism), some drugs (such as corticosteroids), and previous history of fragility fractures. The non-modifiable factors include female gender, family history, race, and early menopause.[45] According to the World Health Organization (WHO) diagnostic criteria, osteoporosis is diagnosed by BMD at the hip or spine, which is below the young normal mean reference population by 2.5 standard deviations (SDs) or more. This is called the T-score, and osteopenia is diagnosed by BMD less than or equal to 1 SD.[6] The guidelines for osteoporosis screening vary greatly in various publications. In general, most organizations recommend that all adults older than 50 years of age with a history of fracture must receive BMD screening.[7] Dual-energy X-ray absorptiometry (DXA) at the hip or spine is the best test for measuring central BMD. An association is present between the T-score values in DXA in patients with osteoporosis or osteopenia and the risk of fractures. A fracture risk assessment tool (FRAX) was designed. It is estimated that for every 1 SD decline in spine BMD, the risk of having a spine fracture increases 2.3 times and the risk of having a hip fracture increases 2.6 times.[89] As the most common bone disease in humans, the prevalence of osteoporosis is steadily increasing due to a growing elderly population, and thus represents a major public health concern with reduced bone strength and a higher risk of fractures.[68] The prevalence of osteoporosis is steadily escalating due to increased life expectancy as a result of developed health services. According to the 2016 WHO report, in the United Arab Emirates (UAE), life expectancy at birth for men was 76 years and for women it was 79 years.[10] The UAE population projection showed that in 2011, 7% of the population were 50 years of age or over and less than 1% were 70 years of age or over. By 2050, it is estimated that 12% of the population will be 50 years or over and 2% will be 70 years or over.[11] MATERIALS AND METHODS Study design The study was performed in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines. Ethical approval number UG-H-18-11-7-10 was obtained from the Research Ethics Committee of the college. The study was conducted on a population sample of national and nonnational people in the UAE. Both men and women were recruited in the study. Data were collected from the patients in six governmental and private hospitals. Research tools A total of 200 male and female participants between the age of 25 and 80 years were recruited in the study. Eighty percent of the sample were women and 20% were men. After obtaining the required consent, each participant was asked to fill a structured questionnaire consisting of 25 questions, which was used as the primary tool for data collection. The questions were formulated both in Arabic and English, it required 3–4min to be completed. BMD of the participants was assessed in the International Radiology Centre and correlated with their data in the questionnaires. DXA scan was used for the measurement of BMD. Data collection and data analysis After ensuring strict confidentiality, data were collected between March 20, 2016 and May 20, 2016. The following information was obtained: Demographic data (gender, age, race, BMI, and occupation) Family history of osteoporosis or osteoporotic fractures Social history and lifestyle, physical activity, and exposure to the sun Dietary habits such as calcium, caffeine, and soft drinks intake Medical history of diseases and medicines. For female participants, number of pregnancies, lactation, and age at menopause were included The following criteria were used to evaluate osteoporosis: Normal BMD: if T-score between +2.5 and –1 Osteopenia: if T-score between –1 and –2.5 Osteoporosis: if T-score below –2.5 The filled questionnaires were coded and data were analyzed statistically using the Statistical Package for the Social Sciences (SPSS) software (version 24; IBM Corporation, Newyork, USA). Spearman’s correlation test was carried out to assess the association between different variables in the study. A P value of less than 0.05 was considered significant. RESULTS Sociodemographic data The sociodemographic background of the study participants is listed in Table 1. A total of 200 participants were included in the study. The control group and the osteoporotic group consisted of 100 participants each, 20% of them were men, whereas 80% of the respondents were women. Table 1: Background demographic data of the respondentsBody mass index The patients with osteoporosis have significantly lower BMI than the control group (P < 0.05). Results showed that 72% of them have a BMI less than 25 kg/m2 (P < 0.05) [Table 2] [Figure 1].Table 2: Body mass index of the respondentsFigure 1: Body mass index (kg/m2) of the respondentsSmoking behavior Regarding smoking behavior, a significant value was evident between smoking and osteoporosis (P < 0.01) as 54% of the patients with osteoporosis were current smokers, whereas 72% of the controls had never smoked before [Table 3] [Figure 2].Table 3: Smoking behavior and intake of milk, coffee, and soft drinks by the respondentsFigure 2: Intake of milk and caffeine and smoking behavior by the respondentsDietary calcium intake The intake of milk and dairy products by the participants was used to assess the dietary calcium intake. The patients with osteoporosis have a significant low calcium intake (P < 0.01), whereas non-osteoporotic control significantly consume more milk and dairy products (P < 0.01). A positive correlation was found between the intake of milk and dairy products and the T-score value of the participants (P < 0.05) [Table 3] [Figures 2 and 3].Figure 3: Correlation between milk intake and T-score in patients with osteoporosisCaffeine consumption Caffeine intake was evaluated in this study by the amount of coffee, tea, or soft drinks consumed by the participants each day. The results showed that the patients with osteoporosis significantly consume more caffeine (P < 0.01). A negative correlation is present between the amount of caffeine intake and T-score value of the participants (P < 0.05) [Table 3] [Figures 2, 4, and 5].Figure 4: Correlation between tea/coffee intake and T-score in patients with osteoporosisFigure 5: Correlation between soft drinks intake and T-score in patients with osteoporosisExercise behavior and exposure to the sun Results showed a significant positive correlation between the duration of exercise and the T-score value of the participants (P < 0.05) [Table 4] [Figure 6].Table 4: Exercise behavior and exposure to sun of the respondentsFigure 6: Correlation between exercise duration and T-score in patients with osteoporosisRegarding the exposure to the sun, the results showed that 96% of the patients with osteoporosis were exposed to the sun for less than 15min, three to four times a week or not exposed at all, whereas most of the normal controls (72%) exposed their bodies to the sun for 16–30min/day, three to four times a week [Table 4] [Figure 7].Figure 7: Sun exposure behavior of the respondentsDiseases and medications Results of the study revealed that 46% of the patients with osteoporosis were diabetic, 42% of them were treated by antidiabetics, 18% had arthritis and 38% had been treated previously by corticosteroids [Table 5].Table 5: Distribution of patients with osteoporosis by their diseases and medicationsNumber of pregnancies and breastfeeding Female participants constituted 80% of the study sample, 75% of the females with osteoporosis were menopausal, 75% of them had three or more pregnancies, and 82.5% of them breastfed their children, whereas these values for the control group participants are 30%, 28%, and 33%, respectively. Results showed a significant positive correlation between the age at menopause and the T-score value of females with osteoporosis (P < 0.05) [Table 6] [Figure 8]. The distribution of patients according to the joint affected by Osteoporosis or Osteopenia is shown in [Figure 9] and [Table 7].Table 6: Distribution of female patients with osteoporosis by number of pregnancies and breastfeedingFigure 8: Correlation between age at menopause and T-score in female patients with osteoporosisFigure 9: Distribution of patients having osteopenia or osteoporosis in wrists, hips, or spineTable 7: Distribution of patients having osteoporosis and/or osteopenia in hips, wrists, and spineDISCUSSION To maintain normal bone structure, a remodeling process that consists of osteoclasts, removing old bone, and osteoblasts, synthesizing new bone, occurs. Hematopoietic progenitors produce osteoclasts, whereas mesenchymal stem cells called marrow stromal fibroblasts produce osteoblasts. This process is controlled by certain circulating hormones, growth factors, and locally produced cytokines through their effects on apoptosis of osteoblasts and osteoclasts. Estrogen deficiency or glucocorticoid excess leads to bone loss because of changes in the production of bone cells. This is caused by the prolongation of the life span of osteoclasts and the shortening of the life span of osteoblasts. On the contrary, drugs that aim to treat or prevent osteoporosis prevent apoptosis of osteoblasts and/or stimulate the apoptosis of osteoclasts.[12] The pathogenesis of osteoporosis is the consequence of various hormonal, genetic, dietary, lifestyle, and physical factors. Genetic factors mainly affect the BMD and bone formation, whereas low levels of estrogen increase parathyroid hormone, and local cytokines are mainly responsible for bone remodeling imbalance.[13] Age and gender In this study, 76% of the patients with osteoporosis were women at or above 50 years of age. Osteoporosis is usually considered a disease of the elderly with low BMD. In a recent study, most of the patients with osteoporosis were in the age groups of 45–49 and 50–54 years.[14] Previous studies showed that women were at an increased risk of developing osteoporosis because of their faulty behavior of physical inactivity, sun-avoidance behavior, low intake of dairy products, and poor diets.[151617] Body mass index The results of this study showed a significant number of patients of osteoporosis with BMI <25 kg/m2, where P < 0.05. Women that have low BMI are at a higher risk of developing osteoporosis. It is reported that one unit change in BMI has a larger effect on the risk of developing osteoporosis than most other modifiable risk factors. To help reduce the risk of osteoporosis, patients should be advised to maintain a weight within the normal range.[1516] The risk of osteoporotic fractures increases in adults who have low BMI of less than 20 kg/m2.[18] On the contrary, patients who are obese (BMI >30 kg/m2) are also at a high risk of developing osteoporosis and fractures because of the risk of repeated falls and the weakness of the skeletal muscles due to loss of its mass as a result of aging.[19] Exercise and physical activity The results of this study showed a significant correlation between the exercise time and the T-score value. Previous studies concluded that physical activity and exercises stimulate skeletal growth and bone strength.[45] Estrogen Estrogen deficiency has a critical effect on the pathogenesis of osteoporosis. The results of this study showed a significant positive correlation between the age at menopause and the T-score value of the female patients. Estrogen has a crucial role in bone formation and physiology. It stimulates the production of T cell cytokines, affects the osteoblastic cell by altering its production of receptor activator of nuclear factor-Kappa B ligand (RANKL) or Osteoprotegerin (OPG), inhibits the differentiation of osteoclasts by direct action, and stimulates the formation of bone performed by osteoblasts and osteocytes, which allows them to enhance their ability to respond to mechanical forces.[2021] Estrogen produces its effect through a specific cell surface receptor called the estrogen receptor alpha (ERα). This receptor binds and then transports estrogen into the nucleus of the cell where certain genes are then activated by the receptor–hormone complex. ERα receptors and estrogen receptor–related receptor alpha (ERRα) are found on the surface of osteoblasts. ERRα may play a supporting role in the regulation of bone cells.[22] Previous studies also suggest that sex hormone–binding globulin may play a significant role in regulating bone cells as well because it facilitates entry of estrogen into cells.[23] Because of the natural drop of estrogen level in postmenopausal women, they are at the highest risk of developing osteoporosis. A previous study showed that it is an increase in bone resorption that might be the driving force for bone loss during estrogen deficiency in postmenopausal women not impaired bone formation as was previously thought.[1] However, other studies indicated that both markers of bone resorption and formation also increased, leading to accelerated bone remodeling at menopause.[2425] Calcium intake and vitamin D Calcium and vitamin D are two pivotal contributors of bone formation and mineralization. The results of this study showed that the patients with osteoporosis have a significant low calcium intake, whereas controls significantly consume more milk and dairy products (P < 0.01). This significant result showed the importance of calcium intake. Results also established a positive correlation between calcium intake and the T-score value of the participants. Vitamin D plays an important role in maintaining calcium homeostasis and bone integrity as it is essential for intestinal calcium absorption.[26] It is estimated that over one billion people around the world have vitamin D deficiency.[2728] Sun exposure is considered as the source of vitamin D, the present results showed a significant value (P < 0.01) as 74% of the patients with osteoporosis exposed their bodies to the sun for 5min or less, three to four times per week, whereas 72% of controls exposed their bodies to the sun for 15–30min, 3 to 4 times a week. A previous study conducted in the UAE showed that 58.2% of the UAE nationals were vitamin D deficient compared to 45% of the patients from other nationalities.[29] In spite of living in sunny areas, such as UAE, Saudi Arabia, and India, young populations have a high prevalence of vitamin D deficiency because of insufficient knowledge and practice of vitamin D and its health implications.[3031] Decreased blood calcium level will lead to secondary hyperparathyroidism. This decrease may result from impaired intestinal calcium absorption due to vitamin D deficiency, aging, or other diseases. Calcitriol, the active form of vitamin D, stimulates the intestinal absorption of calcium and phosphorus. It has an inhibitory effect on the synthesis of parathyroid hormone as well. Therefore, calcitriol deficiency will lead to secondary hyperparathyroidism as well.[32] There is a clear evidence that the risk of having an osteoporotic fracture increases when vitamin D levels are below 50 nmol.[3334] However, a recent study showed that pathological macrophages produced by vitamin D receptor signaling play an important role in the development of myelofibrosis.[35] Smoking The results of this study showed that nicotine has a significant effect on the incidence of osteoporosis (P < 0.01). Smoking has been identified as a modifiable risk factor for low BMD and increased osteoporotic fracture risk.[3637] Smoking behavior should be evaluated when assessing the fracture risk and FRAX.[1638] The role of smoking in decreasing BMD is complicated; smoking is shown to be associated with other risk factors for osteoporosis such as decreased physical activity, low BMI, and poor diet.[38] Nicotine has both direct and indirect effects on BMD. The direct effect is on bone cell proliferation and is described to be biphasic, small doses have a stimulatory effect, whereas toxic large doses have an antiproliferative effect on the proliferation of osteoblasts.[39] This effect on osteoblasts is receptor mediated by the nicotinic acetylcholine receptors, where nicotine in low doses upregulates gene expression of alkaline phosphatase, type 1 collagen, and osteocalcin.[40] Nicotine produces an increased level of tumor necrosis factor α (TNFα) secretion that reduces bone formation by osteoblasts and increases bone resorption by osteoclasts. TNFα has a powerful osteoclastogenic effect through its stimulating effect on RANKL production and by intensifying osteoclasts production.[41] It is strongly supported that RANK/RANKL/OPG systems have a role in regulating bone resorption and the formation of osteoclasts.[42] The main predisposing factor for chronic obstructive pulmonary disease (COPD) has been found to be smoking. The most important factor in managing COPD continues to be the termination of smoking.[43] It has been shown in numerous studies that smokers with COPD have elevated levels of pro-inflammatory cytokines in the form of interleukin-6. In addition, TNFα levels are much higher in COPD smokers than in asymptomatic smokers. This indicates that COPD affects local and systemic inflammatory responses, which in turn affects bone remodeling.[4445] Nicotine has an indirect effect on BMD, which is caused by releasing calcitropic hormones and glucocorticoids, which leads to an increase in bone resorption.[43] Furthermore, smoking has been linked to an increase in the level of cortisol[4446] as well as a decrease in the level of estradiol.[47] Nicotine also harms intestinal calcium absorption, which might lessen the effectiveness of dietary calcium supplements.[48] Also, toxic carcinogenic metabolites of nicotine have also been found to increase osteoclast formation in rats.[49] Moreover, one hip fracture in eight postmenopausal women with osteoporosis is attributable to smoking. This correlation could not be explained by early menopause, low BMI, lower levels of exercise, or by the actions of nicotine on estrogen. This indicates that there is an independent negative effect of nicotine on BMD, which means that smokers lose bone at a faster rate than nonsmokers.[50] CONCLUSION Prevalence of osteoporosis is high in the UAE and is expected to grow due to increased life expectancy and faulty lifestyle of inadequate dietary habits, sun exposure, exercise behavior, and smoking. More intervention should be directed toward changing the modifiable risk factors in the patients with osteoporosis, and more studies should be directed toward osteoporosis in the UAE. Limitations of the study To make the study a polycentric research, it would require greater number of participants from all the emirates of the UAE. Financial support and sponsorship This work is self-funded by the authors. Conflicts of interest There are no conflicts of interest.

Journal of Pharmacy And Bioallied Sciences · 11 citationsread the source →

A youth-focused case management intervention to engage and retain young gay men of color in HIV care.

HIV-positive Latino and African-American young men who have sex with men (YMSM) have low rates of engagement and retention in HIV care. An evaluation of a youth-focused case management intervention (YCM) designed to improve retention in HIV care is presented. HIV-positive Latino and African-American YMSM, ages 18-24, who were newly diagnosed with HIV or in intermittent HIV care, were enrolled into a psychosocial case management intervention administered by Bachelor-level peer case managers at two HIV clinics in Los Angeles County, California. Participants met weekly with a case manager for the first two months and monthly for the next 22 months. Retention in HIV primary care at three and six months of follow-up was evaluated as were factors associated with retention in care. From April 2006 to April 2009, 61 HIV-positive participants were enrolled into the intervention (54% African-American, 46% Latino; mean age 21 years). At the time of enrollment into the intervention, 78% of the YMSM had a critical or immediate need for stable housing, nutrition support, substance abuse treatment, or mental health services. Among intervention participants (n=61), 90% were retained in primary HIV care at three months and 70% at six months. Among those who had previously been in intermittent care (n=33), the proportion attending all HIV primary care visits in the previous six months increased from 7% to 73% following participation in the intervention (p<0.0001). Retention in HIV care at six months was associated with increased number of intervention visits (p=0.05), more hours in the intervention (p=0.02), and prescription of HAART. These data highlight the critical needs of HIV-positive African-American and Latino YMSM and demonstrate that a clinic-based YCM can be effective in stabilizing hard-to-reach clients and retaining them in consistent HIV care.

AIDS care · 54 citationsread the source →

PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?

Major depressive disorder (MDD) is a common and costly disorder which is usually associated with severe and persistent symptoms leading to important social role impairment and increased mortality 1,2. It is one of the most important causes of disability worldwide 3. The high rate of inadequate treatment of the disorder remains a serious concern 1. This review is aimed at summarizing the solid evidence on the etiology and pathophysiology of MDD that is likely relevant for clinical psychiatry. Neurobiological findings are regarded as solid when they are consistent and convergent, i.e., they have been confirmed by several studies using the same method and fit into results from studies using different methodological approaches. Family, twin, and adoption studies provide very solid and consistent evidence that MDD is a familial disorder and that this familiality is mostly or entirely due to genetic factors 4. This important finding suggests that parental social behavior and other familial environmental risk factors are not as important in the pathogenesis of MDD as previously assumed and should not be the major focus of the treatment of the disorder. The above-mentioned studies consistently show that the influence of genetic factors is around 30–40% 4. Non-genetic factors, explaining the remaining 60–70% of the variance in susceptibility to MDD, are individual-specific environmental effects (including measurement error effects and gene-environment interactions). These effects are mostly adverse events in childhood and ongoing or recent stress due to interpersonal adversities, including childhood sexual abuse, other lifetime trauma, low social support, marital problems, and divorce 5,6. These results suggest that there is a huge potential in the prevention of MDD by means of psychosocial interventions (e.g., in schools, at workplace). In addition, these results mirror the clinical practice of empirically validated psychotherapies to treat depression 7,8,9, including interpersonal, psychodynamic and cognitive behavioral psychotherapies and cognitive behavioural analysis system of psychotherapy, which all focus directly or indirectly on interpersonal difficulties and skills. This does not exclude the fact that unidentified non-genetic, non-psychosocial risk factors may also play important roles in some patients (e.g., climatic change, medical conditions). Stress sensitivity in depression is partly gender-specific. While men and women are, in general, equally sensitive to the depressogenic effects of stressful life events, their responses vary depending upon the type of stressor. Specifically, men are more likely to have depressive episodes following divorce, separation, and work difficulties, whereas women are more sensitive to events in their proximal social network, such as difficulty getting along with an individual, serious illness, or death 10. These findings point to the importance of gender-sensitive psychosocial approaches in the prevention and treatment of MDD. In contrast to the very solid evidence from epidemiological studies on broad risk factor domains, there is no solid evidence for specific genes and specific gene-by-environment interactions in the pathogenesis of MDD. Genome-wide association studies have indicated that many genes with small effects are involved in complex diseases, increasing the difficulty in identifying such genes 11. While there has been progress in the search for risk genes for several complex diseases despite this methodological problem 12, psychiatric conditions have turned out to be very resistant to robust gene identification. For example, based on a community-based prospective study, it has been proposed that a specific genetic variation in the promoter region of the serotonin transporter (a target of antidepressant drugs) interacts with stressful life events in the pathogenesis of depression 13. Although there is high clinical and neurobiological plausibility of this interaction, a recent meta-analysis yielded no evidence that the serotonin transporter gene alone or in interaction with psychological stress was associated with the risk of depression 14. The limited success of genetic studies of depression has been related to use of current classification schemas including ICD-10 and DSM-IV. These diagnostic manuals are based on clusters of symptoms and characteristics of clinical course that do not necessarily describe homogenous disorders but instead reflect common final pathways of different pathophysiolgical processes 15,16. The clinician should be aware that family history will continue to be the most solid source of information to estimate the genetic risk of MDD. Corticotropin-releasing hormone (CRH) is released from the hypothalamus in response to the perception of psychological stress by cortical brain regions. This hormone induces the secretion of pituitary corticotropin, which stimulates the adrenal gland to release cortisol into the plasma. The physiologic response to stress is partly gender-specific: women show generally greater stress responsiveness than men, which is consistent with the greater incidence of major depression in women 17. Moreover, men show greater cortisol responses to achievement challenges, whereas women show greater cortisol responses to social rejection challenges 18. Although MDD is considered as a stress disorder, most subjects treated for MDD have no evidence of dysfunctions of the hypothalamic-pituitary-adrenal axis (HPA) 19. However, some subjects with MDD do show abnormalities of that axis and of the extrahypothalamic CRH system 20. Altered stress hormone secretion appeared to be most prominent in depressed subjects with a history of childhood trauma 21. Elevated cortisol may act as a mediator between major depression and its physical long-term consequences such as coronary heart disease, type II diabetes, and osteoporosis 22. The importance of HPA axis dysfunction for the efficacy of antidepressants is a matter of debate 23. This axis is regulated through a dual system of mineralocorticoid (MR) and glucocorticoid (GR) receptors. Decreased limbic GR receptor function 24,25 and increased functional activity of the MR system 26 suggest an imbalance in the MR/GR ratio in stress-related conditions such as MDD. Epigenetic regulation of the glucocorticoid receptors has been associated with childhood abuse 27. Such environmental programming of gene expression may represent one possible mechanism that links early life stress to abnormal HPA axis function and increased risk of MDD in adults. While the CRH stimulation test (dex/CRH test) 28 is a sensitive measure of the HPA axis dysfunction in depression, the specificity of this test for MDD is low. However, non-suppression in the dex/CRH test has consistently predicted increased risk for depressive relapse during clinical remission 23. Additionally, the measurement of waking salivary cortisol concentration has been shown to be a simple and sensitive test for HPA axis hyperactivity in depression 29. Hypercortisolemia is almost exclusively found in subjects with severe and psychotic depression, in whom glucocorticoid antagonists may have some therapeutic effect 30. There is convergent evidence for CRH to play a major role in the pathogenesis of certain types of depression. Levels of CRH in the cerebrospinal fluid are elevated in some depressed subjects 31. Post-mortem studies reported an increased number of CRH secreting neurons in limbic brain regions in depression 32, likely reflecting a compensatory response to increased CRH concentrations 33. In addition, CRH produces a number of physiological and behavioral alterations that resemble the symptoms of major depression, including decreased appetite, disrupted sleep, decreased libido, and psychomotor alterations 34. There is also preliminary evidence that CRH1 receptor antagonists reduce symptoms of depression and anxiety 35. “Sickness behavior” as a result of an activation of the inflammatory response system shares many symptoms with depression, including fatigue, anhedonia, psychomotor retardation, and cognitive impairment. Sickness is mediated by pro-inflammatory cytokines such as interleukin-1α, tumor necrosis factor-α, and interleukin-6, which activate the HPA axis and impair the central serotonin system 36. The prevalence of depression as an unwanted effect of recombinant interferons is around 30% 37. In animals, blocking pro-inflammatory cytokine-mediated signaling produces antidepressant-like effects 38. Clinical data suggest that cytokines may play a role in the pathophysiology of a subgroup of depressed subjects, particularly those with comorbid physical conditions 36. The antidepressant enhancing effect of acetylsalicylic acid 39 points to the possible clinical relevance of psychoneuroimmunology in clinical depression research. Taken together, the laboratory tests with the highest potential to be clinically useful in the care of depressed individuals are based on abnormalities of the neuroendocrine and neuroimmune systems. Despite the large amount of basic science data suggesting that the HPA axis is importantly involved in the pathophysiology of depression, the effect of pharmacological modulation of this neuroendocrine system as antidepressant therapy has been disappointing. The link between childhood trauma and a permanently altered physiologic stress system points to the use of specific psychotherapies in the treatment of depressed patients with a history of early life trauma 40. Most of the serotonergic, noradrenergic and dopaminergic neurons are located in midbrain and brainstem nuclei and project to large areas of the entire brain. This anatomy suggests that monoaminergic systems are involved in the regulation of a broad range of brain functions, including mood, attention, reward processing, sleep, appetite, and cognition. Almost every compound that inhibits monoamine reuptake, leading to an increased concentration of monoamines in the synaptic cleft, has been proven to be a clinically effective antidepressant 19. Inhibiting the enzyme monoamine oxidase, which induces an increased availability of monoamines in presynaptic neurons, also has antidepressant effects. These observations led to the pharmacologically most relevant theory of depression, referred to as the monoamine-deficiency hypothesis. The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. Serotonin is the most extensively studied neurotransmitter in depression. The most direct evidence for an abnormally reduced function of central serotonergic system comes from studies using tryptophan depletion, which reduces central serotonin synthesis. Such a reduction leads to the development of depressive symptoms in subjects at increased risk of depression (subjects with MDD in full remission, healthy subjects with a family history of depression) 41,42, possibly mediated by increased brain metabolism in the ventromedial prefrontal cortex and subcortical brain regions 42. Experimentally reduced central serotonin has been associated with mood congruent memory bias, altered reward-related behaviors, and disruption of inhibitory affective processing 16, all of which add to the clinical plausibility of the serotonin deficiency hypothesis. There is also evidence for abnormalities of serotonin receptors in depression, with the most solid evidence pointing to the serotonin-1A receptor, which regulates serotonin function. Decreased availability of this receptor has been found in multiple brain areas of patients with MDD 43, although this abnormality is not highly specific for MDD and has been found in patients with panic disorder 44 and temporal lobe epilepsy 45, possibly contributing to the considerable comorbidity among these conditions. However, there is no explanation for the mechanism of serotonin loss in depressed patients, and studies of serotonin metabolites in plasma, urine and cerebrospinal fluid, as well as post-mortem research on the serotonergic system in depression, have yielded inconsistent results. There is preliminary evidence that an increased availability of the brain monoamine oxidase, which metabolizes serotonin, may cause serotonin deficiency 46. In addition, loss-of-function mutations in the gene coding for the brain-specific enzyme tryptophan hydroxylase-2 may explain the loss of serotonin production as a rare risk factor for depression 47. Dysfunction of the central noradrenergic system has been hypothesized to play a role in the pathophysiology of MDD, based upon evidence of decreased norepinephrine metabolism, increased activity of tyrosine hydroxylase, and decreased density of norepinephrine transporter in the locus coeruleus in depressed patients 48. In addition, decreased neuronal counts in the locus coeruleus, increased alpha-2 adrenergic receptor density, and decreased alpha-1 adrenergic receptor density have been found in the brains of depressed suicide victims post-mortem 49. Since there is no method to selectively deplete central norepinephrine and no imaging tool to study the central norepinephrine system, solid evidence for abnormalities of this system in depression is lacking. While the classical theories of the neurobiology of depression mainly focused on serotonin and norepinephrine, there is increasing interest in the role of dopamine 50. Dopamine reuptake inhibitors (e.g., nomifensine) and dopamine receptor agonists (e.g., pramipexole) had antidepressant effects in placebo-controlled studies of MDD 51. In the cerebrospinal fluid and jugular vein plasma, levels of dopamine metabolites were consistently reduced in depression, suggesting decreased dopamine turnover 52. Striatal dopamine transporter binding and dopamine uptake were reduced in MDD, consistent with a reduction in dopamine neurotransmission 53. Degeneration of dopamine projections to the striatum in Parkinson's disease was associated with a major depressive syndrome in about one half of cases, which usually preceded the appearance of motor signs 54. Experimentally reduced dopaminergic transmission into the accumbens has been associated with anhedonic symptoms and performance deficits on a reward processing task in subjects at increased risk of depression 55,56. These findings are consistent with the clinical observation that depressed patients have a blunted reaction to positive reinforcers and an abnormal response to negative feedback 57. Almost all established antidepressants target the monoamine systems 58. However, full and partial resistance to these drugs and their delayed onset of action suggest that dysfunctions of monoaminergic neurotransmitter systems found in MDD represent the downstream effects of other, more primary abnormalities. Despite this limitation, the monoamine-deficiency hypothesis has proved to be the most clinically relevant neurobiological theory of depression. New findings on the role of dopamine in depression emphasize the scientific potential of this theory, and promising reports of antidepressant effects of drugs that modulate the dopaminergic system (e.g., pramipexole, modafinil) in difficult-to-treat depression underline its clinical relevance 51,59. Although many historical attempts to localize mental functions have failed, they have considerably contributed to a modern neuroscientific understanding of mental disorders 60. The development of neuroimaging techniques has opened up the potential to investigate structural and functional abnormalities in living depressed patients. Unfortunately, the diversity of imaging techniques used, the relatively small and heterogeneous study samples studied, and the limited overlap of results across imaging paradigms 61 make it difficult to reliably identify neuronal regions or networks with consistently abnormal structure or function in MDD. Functional imaging studies have provided the most limited overlap of findings. This may be due to methodological limitations and/or the complexity of neurocircuitry involved in MDD. A recent meta-analytic study found the best evidence for abnormal brain activity in MDD in lateral frontal and temporal cortices, insula, and cerebellum. In these brain regions activity was decreased at rest, they showed a relative lack of activation during induction of negative emotions, and an increase in activity following treatment with serotonin reuptake inhibitors. Opposite changes may exist in ventromedial frontal areas, striatum and possibly other subcortical brain regions 61. More solid evidence has been provided by structural imaging and post-mortem studies. A recent meta-analytic study on brain volume abnormalities in MDD revealed relatively large volume reductions in the ventromedial prefrontal cortex, particularly in the left anterior cingulate and in the orbitofrontal cortex. Moderate volume reductions were found in the lateral prefrontal cortex, hippocampus and striatum 62. Post-mortem studies consistently identified a reduction in glia cell density in dorsal, orbital and subgenual prefrontal cortices, as well as in the amygdala 63,64. Overall, functional, structural and post-mortem studies suggest that structural and functional abnormalities in the left subgenual cingulate cortex are the most solid neuroanatomical finding in MDD. Volume reduction in this region was found early in illness and in young adults at high familial risk for MDD 65, suggesting a primary neurobiological abnormality associated with the etiology of the illness. Humans with lesions that include the subgenual prefrontal cortex showed abnormal autonomic responses to social stimuli 66, and rats with left-sided lesions in this region had increased sympathetic arousal and corticosterone responses to restraint stress 67. Most importantly, chronic deep brain stimulation to reduce the potentially elevated activity in the subgenual cingulated cortex produced clinical benefits in patients with treatment-resistant depression 68. In summary, despite the considerable heterogeneity of findings from neuroimaging studies, there is convergent evidence for the presence of abnormalities in the subgenual prefrontal cortex in some patients with MDD. Neuroanatomical research in depression is of great clinical interest, since novel antidepressant treatments such as deep brain stimulation can target specific brain regions. In addition, there are promising leads for neuroimaging findings to predict the likelihood of responses to specific treatments 69. Risk factors for depressive episodes change during the course of the illness. The first depressive episode is usually “reactive”, i.e., triggered by important psychosocial stressors, while subsequent episodes become increasingly “endogenous”, i.e., triggered by minor stressors or occurring spontaneously 70. There is consistent evidence that the volume loss of the hippocampus and other brain regions is related to the duration of depression 71, suggesting that untreated depression leads to hippocampal volume loss, possibly resulting in increased stress sensitivity 72 and increased risk of recurrence 73. Glucocorticoid neurotoxicity, glutamatergic toxicity, decreased neurotrophic factors, and decreased neurogenesis have been proposed as possible mechanisms explaining brain volume loss in depression. There is no solid evidence on of these since there are no imaging to directly and neurotrophic processes in neurotrophic factor has considerable Specifically, studies have shown between and in hippocampal as well as expression of following antidepressant treatment The clinician should be aware of the potentially effect of depression and treat depressed patients as early and as A of studies consistently showed reductions in acid concentrations in the prefrontal and cortex in depression This may reflect stress since psychological stress to presynaptic of prefrontal neurotransmission low concentration may reflect reduction in the density and of In addition, chronic stress may reduce receptor possibly through changes in evidence of the hypothesis of depression the lack of effects of drugs on depressive symptoms and prefrontal concentration in subjects with MDD of evidence suggest a dysfunction of the neurotransmitter system in a of the receptor produced and large antidepressant effects in patients with treatment-resistant MDD inhibitors of release (e.g., antidepressant abnormal levels were found in depressed subjects as by and there is evidence for abnormal signaling in post-mortem Since is the major neurotransmitter involved in almost every brain the of the specific role of in depression (e.g., there are promising leads that the receptor is involved in MDD and are diagnostic for MDD, suggesting regulation in depressed patients. In addition, some depressive symptoms may show psychomotor of of positive and negative and a subgroup of patients with MDD may have a disorder In healthy young subjects, changes in the of the had specific effects on subsequent mood In depressed patients, of can have antidepressant on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of on these abnormalities have been hypothesized to be associated with MDD The association between of the and in cortisol in some subjects with and the effect of antidepressants on of and to the of this hypothesis Despite of the many promising the and genetic of this hypothesis are It remains to be antidepressant effects of such as directly to of The and of the neurobiological of depression are in 1. The many theories of depression and the relatively low response rate of all antidepressant treatments a hypothesis of and suggest that depression is a clinically and heterogeneous disorder. This research on of the response to therapeutic interventions using such as neuroimaging and neuroendocrine tests in with for with to stress sensitivity and antidepressant The of of therapeutic will for the development of that has the potential to interventions and to up pathways in the of novel therapeutic approaches.

World Psychiatry · editorial or comment · 607 citationsread the source →

Does combined cognitive training and physical activity training enhance cognitive abilities more than either alone? A four-condition randomized controlled trial among healthy older adults.

Cognitive training and aerobic training are known to improve cognitive functions. To examine the separate and combined effects of such training on cognitive performance, four groups of healthy older adults embarked on a 4 months cognitive and/or mild aerobic training. A first group [n = 33, mean age = 80 (66-90)] engaged in cognitive training, a second [n = 29, mean age = 81 (65-89)] in mild aerobic training, a third [n = 29, mean age = 79 (70-93)] in the combination of both, and a fourth [n = 31, mean age = 79 (71-92)] control group engaged in book-reading activity. The outcome was a well-validated multi-domain computerized cognitive evaluation for older adults. The results indicate that, when compared to older adults who did not engage in cognitive training (the mild aerobic and control groups) older adults who engaged in cognitive training (separate or combined training groups) showed significant improvement in cognitive performance on Hand-Eye Coordination, Global Visual Memory (GVM; working memory and long-term memory), Speed of Information Processing, Visual Scanning, and Naming. Indeed, individuals who did not engage in cognitive training showed no such improvements. Those results suggest that cognitive training is effective in improving cognitive performance and that it (and not mild aerobic training) is driving the improvement in the combined condition. Results are discussed in terms of the special circumstances of aerobic and cognitive training for older adults who are above 80 years of age.

Frontiers in aging neuroscience · 143 citationsread the source →

Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in brain of an Alzheimer's disease mouse.

Polyphenols extracted from grape seeds are able to inhibit amyloid-beta (Abeta) aggregation, reduce Abeta production and protect against Abeta neurotoxicity in vitro. We aimed to investigate the therapeutic effects of a polyphenol-rich grape seed extract (GSE) in Alzheimer's disease (AD) mice. APP(Swe)/PS1dE9 transgenic mice were fed with normal AIN-93G diet (control diet), AIN-93G diet with 0.07% curcumin or diet with 2% GSE beginning at 3 months of age for 9 months. Total phenolic content of GSE was 592.5 mg/g dry weight, including gallic acid (49 mg/g), catechin (41 mg/g), epicatechin (66 mg/g) and proanthocyanidins (436.6 mg catechin equivalents/g). Long-term feeding of GSE diet was well tolerated without fatality, behavioural abnormality, changes in food consumption, body weight or liver function. The Abeta levels in the brain and serum of the mice fed with GSE were reduced by 33% and 44%, respectively, compared with the Alzheimer's mice fed with the control diet. Amyloid plaques and microgliosis in the brain of Alzheimer's mice fed with GSE were also reduced by 49% and 70%, respectively. Curcumin also significantly reduced brain Abeta burden and microglia activation. Conclusively, polyphenol-rich GSE prevents the Abeta deposition and attenuates the inflammation in the brain of a transgenic mouse model, and this thus is promising in delaying development of AD.

Neurotoxicity research · 143 citationsread the source →

Problematic Internet use: an overview

The “global village”, a metaphor used to describe how the Internet has shortened distances and facilitated the flow of information, has grown to over one billion users 1. Statistics from across the world highlight its reach and penetrance: 90% of South Korean households connect to high-speed, inexpensive broadband 2; Londoners spend an average of 45 days a year online, more than they spend watching TV 3; and the rate of increase in the number of Internet users in Africa and the Middle East exceeded 1,300% between 2000 and 2009 4. For the majority of Internet users, the World Wide Web represents a tremendous wellspring of opportunity that enhances well-being. For others, however, it can lead to a state that appears to meet the DSM definition of a mental disorder, described as a “clinically significant behavioral or psychological syndrome…that is associated with present distress… or with a significantly increased risk of suffering death, pain, disability, or an important loss of freedom” 5. Scientific understanding of that state has lagged behind media attention 6, in part because of inconsistency in defining the problem 7, disagreement about its very existence 8, and the variable research methodology used in studying it. Still, a body of data by scientists from the East and West (with the East increasingly leading the way) tells a cautionary tale about the Internet's potential to bring about psychological harm. In 1996, the psychologist K. Young became the first to publish a detailed case report of problematic Internet use 9. Her “patient zero” was a non-technologically oriented 43-year-old homemaker with a “content home life and no prior addiction or psychiatric history”, who, within three months of discovering chat rooms, was spending up to 60 hours per week online. She reported feeling excited in front of the computer, and depressed, anxious, and irritable when she would log off. She described having an addiction to the medium “like one would to alcohol”. Within one year of purchasing her home computer, she was ignoring household chores, had quit social activities she used to enjoy, and had become estranged from her two teenage daughters and her husband of 17 years. Based on this and other patients she interviewed, Young proposed the first set of diagnostic criteria for what she termed “Internet addiction”. She modeled them on the DSM-IV definition for substance dependence because of similarities she observed with the states of tolerance (needing more of the substance to achieve the same effect) and withdrawal (psychological and physical discomfort upon reducing or stopping the substance) 9. Others conceptualized problematic Internet use as a behavioral addiction not involving an intoxicant 10, and Young subsequently updated her definition, adapting the DSM-IV criteria for pathological gambling, an impulse control disorder often described as a behavioral addiction, into her Diagnostic Questionnaire 11 (Table 1). The questionnaire, which required at least five of the eight criteria be met for the Internet addiction diagnosis, has not received adequate psychometric testing. Shapira et al 12 proposed five years later a more inclusive diagnostic schema in the general style of the impulse control disorders. They argued that definitions based solely on substance dependence or pathological gambling were too narrow to capture the population of problematic Internet users and could lead to premature conclusions about the new disorder and the patients. They eschewed the “Internet addiction” label for lack of scientific proof for true addiction and favored the less controversial “problematic Internet use”, defining it as: a) maladaptive preoccupation with Internet use, experienced as irresistible use for periods of time longer than intended; b) significant distress or impairment resulting from the behavior; and c) the absence of other Axis I pathology that might explain the behavior, such as mania or hypomania. To date, only two studies have attempted to develop diagnostic criteria empirically by testing them against the diagnosis made on the basis of a systematic psychiatric interview. Ko et al 13 tested a set of criteria in 468 Taiwanese high school students. Starting with 13 candidate criteria, they eliminated those with low diagnostic accuracy, and determined that a cutoff of six out of the nine remaining criteria had the best diagnostic accuracy while maintaining high specificity (97.1%) and acceptable sensitivity (87.5%). The criterion for functional impairment was listed separately as criterion B and was required for the diagnosis (Table 2). In a second study, Ko et al 14 confirmed the diagnostic accuracy of their criteria in an older cohort of 216 Taiwanese college students. However, the relatively small size of both studies and the non-representative nature of the groups studied limit the applicability of the proposed criteria to the general population. Several assessment scales have been proposed to screen for, and help diagnose, problematic Internet use. As a group, these instruments show no consensus on the underlying dimensions that constitute the condition 6,15. In addition to Young's Diagnostic Questionnaire, two are in relatively common use in research and/or clinical settings: Young's Internet Addiction Test 16 and the Chen Internet Addiction Scale 17. Young's Internet Addiction Test 16 consists of 20 “how-often” questions, each rated on a scale of 1 to 5 (1=rarely; 2=occasionally; 3=frequently; 4=often; 5=always.) A score of 80 or above is consistent with problematic use (Table 3). The psychometric properties of the instrument were studied in 86 subjects 18. Six factors were extracted from the questionnaire: salience, excessive use, neglect of work, anticipation, lack of control, and neglect of social life. These factors showed good concurrent validity and internal consistency. Salience explained most of the variance and was also found to be the most reliable as indicated by its Cronbach's alpha. However, the selection bias introduced by online recruitment and the small size of the study limit its value. The Chen Internet Addiction Scale 17 is a self-report instrument composed of 26 items rated on a 4-point Likert scale (adapted in Table 4). It assesses five domains of Internet-related problems: compulsive use, withdrawal, tolerance, interpersonal and health consequences, and time management difficulties. Scores range from 26 to 104. In a study of 454 Taiwanese adolescents who completed the scale and received a structured diagnostic interview, a cutoff of 64 was shown to have high diagnostic accuracy and specificity (88% and 92.6%, respectively) 19. The internal reliability of the scale and subscales in the original study ranged from 0.79 to 0.93 17. Due to the lack of consensus on diagnostic criteria and the dearth of large epidemiological studies, the prevalence of problematic Internet use in the general population has not been established. Overall, prevalence surveys conducted in various countries fall into two main categories, online vs. offline studies, with the former typically yielding higher rates, most likely because of inherent selection bias 20. Only two epidemiological studies exploring the prevalence of problematic Internet use in the general population have been published. One was conducted in the US, the other in Norway 20,21. The US study used random-digit telephone dialing (cellular phone numbers were not included) to interview 2,513 adults taken from all 50 states in a manner proportional to the population in each state 20. More than half of the people reached agreed to be interviewed. Participants’ average age was 48, and 51% fell in the middle class socioeconomic stratum. 68.9% were regular Internet users. The authors’ diagnostic definition, based on published criteria and on similarities with impulse control disorders, substance dependence and obsessive-compulsive disorder, required: a) Internet use that interferes in personal relationships; b) preoccupation with the Internet when offline; c) unsuccessful attempts at quitting or cutting down; and d) staying online longer than intended. This definition yielded a point prevalence of 0.7%. Less stringent definitions yielded higher prevalence rates, and individual features consistent with problematic Internet use were endorsed by as many as 13.7% (respondents who found it hard to stay offline for days in a row). In the second study, Bakken et al 21 mailed Young's Diagnostic Questionnaire to 10,000 inhabitants of Norway, randomly selected from a database of the entire population. 3,399 completed questionnaires were returned (a somewhat lower response rate than the US study). Recipients of the mailed questionnaire also had the option of completing it online. Among respondents, 87% were Internet users. The prevalence of “addicted Internet use” (≥5 questions answered “yes”) was calculated to be 1%, whereas the prevalence of “at risk” Internet use (3–4 questions answered “yes”) was 5.2%. Multivariate analysis showed young age, male gender, higher educational achievement, and financial stress to be positively associated with “problematic Internet use” (defined by the authors to include both “Internet addicts” and “at risk” respondents). Prevalence rates among adolescents have been researched more extensively, perhaps because the so-called “digital natives” grew up incorporating the Internet in many aspects of life and as a result are perceived to be at higher risk. However, even when online-based surveys are excluded, the results can vary widely and are difficult to compare, due to differences in Internet access, recruitment methodology, the exact age bracket studied, and the definitions utilized. Considering only relatively large and offline studies, research from China 22, South Korea 23,24, Greece 25, Norway 26, and Iran 27 has yielded prevalence estimates ranging between 2% and 11%. Problematic Internet use has not been incorporated into large-scale epidemiological studies aimed at estimating the relative prevalence of mental disorders. Still, a review of published studies reveals that the presence of other psychiatric conditions in patients with problematic Internet use is the rule rather than the exception 6. The studies, however, were not designed or statistically powered to detect the nature of the association (cause, effect, or independent). In Bakken's general-population study 21, based on subjects’ self-report, 41.4% of Internet “addicts” reported feelings of depression in the 12-month period prior to the study, compared to 15.8% of non-problematic users. Sleep disturbances, anxious feelings, and alcohol and substance abuse were also more common (38.6% vs. 26.4%, 36.4% vs. 5%, and 13.6% vs. 1.1%, respectively). However, the questions used to assess co-occurring psychological impairment were not based on established criteria for mood, sleep, anxiety, or substance use disorders. Two US case series involved face-to-face interviews of adult patients with problematic Internet use. Black et al 28 assessed 21 subjects with the Diagnostic Interview Schedule and found the lifetime prevalence of mood disorders and major depression to be 33% and 15%, respectively. Further, 38% had a lifetime substance use disorder and 19% had a lifetime diagnosis of anxiety disorder. In a case series that included 20 patients, Shapira et al 29 found a very high (70%) lifetime prevalence for bipolar affective disorder, type I or II, compared with 15% for major depression. Fifty-five percent had a lifetime prevalence of substance abuse, and 45% met criteria for social anxiety disorder. Fifty percent of subjects had a lifetime diagnosis of an impulse control disorder. The authors highlight their observation that patients’ Internet-related symptoms were more impulsive and egosyntonic than compulsive and egodystonic, concluding that problematic Internet use resembles the DSM-IV definition of an impulse control disorder more closely than that of obsessive-compulsive disorder. Our clinical experience supports this conclusion. As a group, surveys conducted among high school and college students show similarly high comorbidity rates with mood and anxiety disorders, but a link between attention-deficit/hyperactivity disorder (ADHD) and problematic Internet use seems more obvious than among adults. One study in 752 South Korean elementary students found that 33% of those with ADHD also met criteria for problematic Internet use 30. Another study in 216 Taiwanese college students showed that 32% subjects with problematic Internet use also had ADHD compared to only 8% of regular Internet users 31. Whether Web-based activities appeal to the short attention span of ADHD sufferers or whether excessive Internet use may cause inattention remains to be elucidated. The clinical evaluation of the patient with problematic Internet use should include a careful assessment of the comorbid conditions frequently present. Those should then be treated according to established treatment guidelines. To the extent that the Internet-related problem may stem from another diagnosis (e.g., a patient with severe social anxiety who starts leading a “virtual” life at the expense of offline interactions), it might improve as the primary condition is addressed. Pharmacotherapeutic and psychotherapeutic interventions specific to problematic Internet use have not yet received adequate testing in large, rigorous studies. Pharmacotherapy often begins with selective serotonin reuptake inhibitors (SSRIs). However, while effective in treating obsessive-compulsive disorder, SSRIs have shown mixed results in impulse control disorders 32,33,34,35–36. In light of the greater similarity between problematic Internet use and impulse control disorders compared to obsessive-compulsive disorder 29, it is unclear whether SSRIs will ultimately prove beneficial, and no double-blind placebo-controlled studies have been published so far. One discontinuation study tested escitalopram, 20 mg/day, in 19 subjects with problematic Internet use 37. During the 10-week open-label phase, subjects showed significant decreases in weekly hours spent online (from a mean of 36.8 hours to 16.5 hours) and improvement in global functioning. At the end of the 10 weeks, subjects were blindly randomized to either continued escitalopram treatment or to placebo. Beyond that, they were followed for 9 weeks. No significant difference was seen between the two groups at the end of the second phase, as gains achieved at week 10 were maintained in both treatment groups. The authors speculate that nine weeks may have not been sufficient for the effect to be lost in the placebo group or for additional gains to be made in the escitalopram group, but do not rule out the possibility that the improvement seen in the open-label phase may have been a placebo response. One case study reported successful treatment with naltrexone 38, a drug that has shown benefit in other impulse control disorders 39,40. The patient was a 31 year old male with compulsive cybersexual behavior who had failed antidepressants, group and individual psychotherapy, Sexual Addicts Anonymous, and pastoral counseling. Naltrexone (150 mg/day), gradually added to a stable dose of sertraline which on its own had been ineffective in treating his problematic Internet use, helped induce a three-year remission. The authors hypothesize that, by blocking the capacity of endogenous opioids to trigger dopamine release in response to reward, naltrexone may block the reinforcing nature of compulsive Internet sexual activity. Another case study reported the successful use of an atypical antipsychotic, quetiapine, 200 mg/day, gradually added to citalopram, in a 23 year old subject with problematic Internet use 41. The improvement was maintained at four-month follow-up. More recently, a study tested methylphenidate in 62 children with ADHD who were Internet video game players 42. Participants’ average age was around 9. After 8 weeks of treatment (average dose 30.5 mg/day), Internet usage decreased significantly and correlated with reduction in ADHD symptoms. The authors cautiously suggest that methylphenidate might be beneficial as a treatment for problematic Internet use, especially when co-occurring with ADHD. Of the psychotherapy approaches used, cognitive behavioral therapy (CBT) has received the most empiric investigation. The largest study enrolled 114 adult subjects and employed CBT interventions including: keeping a daily log of Internet activity, teaching time management skills, and confronting cognitive distortions and rationalizations frequently used by patients to justify continued Internet usage, such as “just a few more minutes won't hurt” 43. Most subjects were able to control their symptoms by the eighth session, and improvement was sustained over a 6-month follow-up. For children and adolescents, family-based interventions that improve communication and teach family monitoring of Internet use can be helpful 44. However, the intensive (and typically very expensive) residential treatment options that have received much media attention have undergone little empiric investigation to warrant a strong recommendation 2,45. The same applies to online treatment websites that encourage the person with problematic Internet use to “click here if you are addicted to the Internet”. For a medium that has so radically changed the way we conduct our lives, the Internet's effects on our psychological health remain understudied. Simply stating that similar fears were raised when the radio, movies and early video games were introduced is not sufficient: the immersive and interactive qualities of the virtual world, and its sheer penetrance, make it potentially more serious. Also deserving of exploration are the more subtle psychological changes that occur in the virtual world, such as online disinhibition and increased risk-taking 46. Those changes are not necessarily evidence of “Internet addiction”, and may not be pathological, but, as important features of the new virtual psychology, should also be studied. As our field continues to debate whether their condition belongs in the next edition of the DSM 47, patients continue to present with symptoms born out of the digital age, and their symptoms are changing as the technology evolves from browsers, to “crackberries”, to “smart phones” that combine texting, talking, video games, and browsing in one device that to many is like a new appendage. Even the “problematic Internet use” designation now seems outdated, which is why some have wisely opted for “pathological use of electronic media”, instead 47. Technology, like media outlets, remains far ahead of scientific investigation. Given the dramatic changes that our society is undergoing as a result of the Internet revolution, it behooves us to try to bridge the gap.

World Psychiatry · 340 citationsread the source →

Predictors of referral for specialized psychosocial oncology care in patients with metastatic cancer: the contributions of age, distress, and marital status.

Purpose: This study examines the rate and prediction of referral for specialized psychosocial oncology care in 326 patients with metastatic GI or lung cancer. Patients and methods: Referral information was abstracted from medical records and hospital databases. Patients completed measures of psychosocial and physical distress and functioning. Results: Routine referral occurred in 33% of patients, and in 42% and 44%, respectively, of those scoring high on measures of depression (Beck Depression Inventory [BDI]-II >or= 15) and hopelessness (Beck Hopelessness Scale >or= 8). Univariate analyses indicated that referral was associated with younger age, unmarried status, living alone, presence of more depressive symptoms, hopelessness, and attachment anxiety, and with less social support, self-esteem, and spiritual well-being (all P < .05). Among the significantly depressed (BDI-II >or= 15), 100% of those less than 40 years of age, but only 22% of those age 70 years or older were referred. Multivariate analyses indicated that referral was associated with younger age, unmarried status, and presence of more depressive symptoms. Moreover, increasing age was associated with a progressively lower likelihood of referral independent of the level of distress. Conclusion: Routine referral of patients with metastatic cancer for psychosocial oncology care was predicted by presence of more severe depressive symptoms, younger age, and unmarried status. The rate of referral progressively declined with each decade of age, even among those with significant distress. These findings are consistent with some aspects of Andersen's model of health care utilization. The extent to which referred patients represent those who are most likely to benefit deserves further investigation.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 84 citationsread the source →

Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study.

Objectives: To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. Design: A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. Setting: EPIC II included 1265 intensive care units in 76 countries. Patients: Patients in participating intensive care units on study day. Interventions: None. Measurement and main results: Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. Conclusion: Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use.

Critical care medicine · 276 citationsread the source →

Prediction and prevention of schizophrenia: what has been achieved and where to go next?

Since the traditional clinical paradigm has been replaced by the modern molecular one, medicine set off into new directions. “Prediction”, “prevention” and “personalization” are the programmatic key words of this new approach. Like other medical disciplines, psychiatry has broadened its focus from diagnosis and treatment to the detection and estimation of the risk of disease development, the prediction of its onset and strategies to avoid its manifestation 1,2,3,4. Although treatment of schizophrenia has greatly advanced over the last decades, a significant number of patients continue to take an unfavorable chronic course 5,6. This makes schizophrenia the leading cause for permanent occupational disability among people under 40 years of age in Germany 7, and the 8th most common cause for disability adjusted life years (DALYs) lost among the 15 to 34-year olds worldwide 8, despite its low prevalence. Moreover, schizophrenia involves tremendous direct and indirect societal costs 9 and a huge burden on patients and their families 8,10. It is becoming increasingly clear that schizophrenia is a complex disorder with polygenic heredity and that its pathogenesis is greatly influenced by interactions between different genes and between genes and environment. Associations to variants of the genes for dysbindin and neuregulin-1, the genetic locus G72 and the DAOA (D-amino acid oxidase activator) gene have now been repeatedly confirmed. As with all other complex diseases, research is focusing now on characterizing the polygenetic predisposition and clarifying its influence on the development of the phenotype 11. Research methods range from molecular genetics via proteome research to cell biology, neurophysiology, brain structural and functional imaging and neuropsychology. With all these methods, several indicators for an increased risk of schizophrenia have been identified. However, the currently recognized neurobiological risk factors are not sufficiently predictive to allow the development and application of “selective” prevention measures targeting asymptomatic persons at risk. For neuro-psychological risk factors, this has just become evident in the large-scale attempt of the North American Prodrome Longitudinal Study (NAPLS) group to improve their multivariate model by integrating the examined neurocognitive variables 12. There are also established environmental risk factors for schizophrenia, such as pregnancy or birth complications, growing up in a large city, IQ low but normal and drug consumption. However, with odds ratios around 2, each of these factors appears to increase the lifetime risk of the disease only slightly 13. Thus, the currently known risk factors, either alone or taken together, cannot be used for prediction and prevention without knowledge of the complete predispositional basis and the gene-gene and gene-environment interactions, which are probably numerous. In view of this situation, it may be argued that the current efforts towards prediction and prevention are still premature and that further progress of etiological research is needed. However, a different perspective has emerged from the work of the centers for early recognition and prevention, established first in Melbourne, Australia and in Cologne, Germany in the mid 1990s, and later on in many other places around the world. This resulted from retrospective research of the early course of psychosis, in which the pathophysiologically active disturbances in brain development extend beyond early abnormalities in behavior into psychopathologically definable early risk and ultra high risk (UHR) symptoms, depending on the individual combination of stressors and resilience factors. First episode psychosis (FEP) research has shown that the outbreak of the disease is preceded in about 70% to nearly 100% of cases by an initial prodrome, which lasts for an average of five to six years. Even in highly developed health care systems, an average of one year thereafter elapses from the first manifestation of psychotic positive symptoms to the initiation of adequate treatment 14,15. The period over which the FEP remains untreated (duration of untreated psychosis, DUP) correlates with: delayed and incomplete remission of the symptoms; necessity of more protracted treatment and greater risk of relapse; lower compliance, greater burden on the family, and a higher level of “expressed emotion”; increased risk of depression and suicide; greater impact on the individual's employment or education; increased drug abuse and delinquent behavior; markedly increased costs of treatment 16. These correlations have recently been confirmed by a meta-analysis 17, with coefficients ranging from 0.285 to 0.434 (95% CI). This does not only provide strong arguments in favor of treating the FEP as early as possible, but has also led to a systematic effort to decrease the incidence of psychosis through indicated prevention. Two important studies concerning the early stage prior to the conversion to FEP have demonstrated that the earliest and most common symptoms, which generally dominate during the prodrome, are unspecific and cannot be distinguished from impairment in mood, drive, contact, and concentration of depressive episodes. These are the Age-Beginning-Course (ABC) study of schizophrenia, a retrospective study with optimized methods 14, and the Cologne Early Recognition (CER) Study, a long-term prospective study with an average follow-up period just below 10 years 18. These studies also found striking cognitive impairments in the form of self-experienced disturbances in thought, speech, and perception processes. This subgroup of so-called basic symptoms, which were found in more than a quarter of patients, had high specificity and a high positive predictive power, accompanied by only low rates of false positive predictions 19,20,21. Basic symptoms were first operationalized in the Bonn Scale for the Assessment of Basic Symptoms (BSABS). Shorter versions of the scale for adults and for children and adolescents — the Schizophrenia Proneness Instrument, Adult version (SPI-A) and the Schizophrenia Proneness Instrument, Child and Youth version (SPI-CY) — were later developed from dimensional analyses 22,23,24. While the BSABS only allows an assessment of the current state, the SPI-A and the SPI-CY also allow severity ratings according to the maximum frequency of occurrence within the past 3 months. In the CER study, 385 patients who were presumably in the prodromal phase of schizophrenia were followed up for an average of 9.6 (±7.6) years past baseline. Twenty percent of the initial criterion-positive cases (1 of 66 basic symptoms) who agreed to be followed up developed schizophrenia after 12 months, a further 17% after 24 months, a further 13% after 36 months, and finally a total of 70% after an average of 4.5 years. Thus, only 30% did not convert to schizophrenia. The overall presence/absence of at least one basic symptom correctly predicted presence/absence of a subsequent transition to schizophrenia in 78.1% of cases. From further analyses, two partially overlapping basic symptom criteria for defining at risk mental states (ARMS) for psychosis, primarily schizophrenia, were developed (Table 1). The first criterion, which consists of ten cognitive-perceptive basic symptoms and is abbreviated as COPER, was based on findings concerning the predictive accuracy of individual basic symptoms 18,25. The second was based on a methodological re-analysis of the same data set, in which a cluster of nine cognitive basic symptoms had repeatedly been selected as the most predictive. This cluster was called “cognitive disturbances” (COGDIS). In terms of general predictive accuracy, the two criteria slightly differed in the CER study, as COGDIS tended to be more conservative than COPER, i.e. to perform better in ruling in subsequent schizophrenia at the cost of performing worse in ruling it out. The transition rate throughout the average follow-up period of roughly 10 years was 65% for COPER and 79% for COGDIS, with the majority of transitions occurring within the first 3 years past baseline. In a second prospective study 26, conducted with the SPI-A and with a systematic follow-up of 24 months, 38% of the initially included 146 at-risk subjects developed a frank psychosis, mainly schizophrenia, within 12.3 (±10.4) months on average (1–48; median=9) according to COPER. Thus, the positive results of the CER study were confirmed. Again, COGDIS appeared to be more specific but less sensitive than COPER. As a consequence of these findings, predictive basic symptoms have been established as a set of criteria for risk assessment in international research on the early recognition of psychosis. In particular, the German Research Network on Schizophrenia used these symptoms, together with a combined criterion of functional deterioration and biological risk, in defining an “early at-risk of psychosis state” (ERPS), thereby suggesting a clinical risk staging model (Figure 1). Early and late initial prodromal state: a clinical staging approach The positive symptoms typical of schizophrenia — such as delusions, hallucinations or formal thought disorders — often first appear in an attenuated or transient form during the initial prodromal phase. These symptoms provide a valid prediction of conversion into FEP, particularly in the short term. Warning signs of this sort have been used as ultra-high risk (UHR) criteria 27,28. Notwithstanding their differences across studies, these criteria are generally composed of three alternative elements: attenuated positive symptoms (APS), brief limited intermittent psychotic symptoms (BLIPS), or a combination of one or more risk factors (always including genetic risk) and functional decline within a certain recent period. For the ascertainment of the UHR criteria, the Melbourne group gradually developed a specific instrument, the Comprehensive Assessment of At Risk Mental States (CAARMS) 29. Based on the Australian definition of the UHR criteria, the Structured Interview for Prodromal Syndromes (SIPS), the Scale for Prodromal Syndromes (SOPS) and, subsequently, the Criteria of Prodromal Syndromes (COPS) were developed 30,31. Different UHR-related approaches to an early detection of FEP, particularly schizophrenia, were developed by the Hillside Recognition and Prevention (RAP) program in New York 32 and the Basel Früherkennung von Psychosen (FEPSY) study 33. There have been at least 15 prediction studies using UHR criteria, some of which with large samples 34,35,36,37,38,39,40,41. The 12-month rates of transition into FEP published so far range between approximately 13% and 50%. A substantial variance is even observed with comparable observation periods in the same center 34,35. Yet, as the annual incidence for all forms of psychosis in the general population is only about 0.034% 42, even the lowest conversion rates still indicate a dramatic increase in the relative risk of illness, at least in the help-seeking samples of specialized centers. Table 2 depicts the predictive accuracy measures published so far, with the last five listed studies representing secondary predictor analyses of samples meeting at risk criteria. As a result, in the German Research Network on Schizophrenia, the UHR approach was combined with the basic symptom approach and applied in a slightly modified form for the definition of “late at-risk of psychosis state” (LRPS) (Figure 1). This clinical staging model, which suggests a syndromal sequence for the development of FEP progressing from unspecific prodromal symptoms to predictive basic symptoms, and then to APS, to BLIPS and to full-blown psychotic symptoms, was recently strongly supported 15. Universal or selective prevention measures target healthy population groups or clinically still healthy risk carriers, respectively 43. Indicated prevention, instead, targets individuals with basic symptoms and UHR symptoms. Even at the early stages when these individuals seek advice and help at the early recognition and prevention centers, they must be regarded as ill and in need of treatment. Furthermore, the impending deterioration of psychosocial performance in schizophrenia often already occurs in the initial prodromal phase, even prior to the conversion into FEP 14,15. These clinical and psychosocial impairments justify defining the interventions in EPRS and LPRS as indicated prevention, pursuing the following three objectives: a) improvement in the current burden of prodromal symptoms; b) avoidance or perhaps delay in the development of psychosocial handicap; c) prevention of or at least delay or attenuation of psychosis. Five international intervention studies have attempted to find out whether or to what extent these three objectives can be reached 44,45,46,47,48,49,50,51 (Table 3). The preventive measures used were either cognitive behavioral therapy (CBT), adapted to the requirements of the persons at risk, or atypical antipsychotics (risperidone, olanzapine, and amisulpride). These were randomized controlled studies, but there were problems with the blinding condition in the two CBT interventions. This and other methodological shortcomings currently limit conclusions and have encouraged the research groups working in this area to set up new, optimized intervention studies. For example, the protocol of the ongoing parallel group PREVENT study includes careful comparative analyses and superiority and inferiority tests of the psychological and pharmacological treatments 52. A staging of risk, thereby implying a temporal dimension, was considered for the first time in the two intervention studies of the German Research Network on Schizophrenia. One of these studies covered ERPS and only offered CBT as a preventive measure 49,50. The other study was designed for LRPS and used only preventive treatment with amisul-pride 51. When the symptom development in the initial prodromal state follows the sequence shown in Figure 1, it would be beneficial for scientific and especially ethical reasons to focus on psychological interventions in ERPS, which are well tolerated and highly accepted. As soon as the first attenuated or transient psychotic symptoms occur, it seems justifiable to apply well tolerated antipsychotics with few side effects. This differential prevention strategy is now pursued in all German early recognition centers and is also increasingly gaining support in other countries. Another pharmacological option is aripiprazole, tested in a pilot study in UHR states 53. Its possible preventive effects are currently being analyzed in the PREVENT study. Antidepressants were used in a naturalistic, non-randomized observational study of an adolescent sample employing only the APS criterion for inclusion, but, for methodological reasons, this study does not allow any conclusion about differential preventive effects of these medications 54. A critical evaluation of the achievements over the past 15 years through continuous efforts to enhance prediction and prevention of psychoses, particularly of schizophrenia, reveals quite impressive results. However, the results achieved thus far need to be evaluated in the light of the ambitious, initially mentioned objectives of modern predictive and preventive medicine. Once predictive basic symptoms and UHR symptoms have occurred, the underlying pathophysiological process might have already progressed. For such a complex disease with a long-term course and a pre-dispositional basis, this kind of risk identification and risk-oriented prevention may possibly come too late. A more substantial reduction in incidence could be reached with selective and universal prevention measures. Therefore, symptom-based prediction and prevention need to be further developed into the direction of selective prevention for symptom-free risk carriers. In the future, it is necessary to strive for: a) an improvement of risk enrichment with the inclusion of biological risk factors; b) a stronger individualization of the risk estimation by stratification; c) the inclusion of sub-psychotic mental states, as cross-sectionally by current at risk criteria, in the the application of prevention strategies more with the of the the initial prodromal phase for as as then most of the follow-up periods shown in Table 2 are not to the transition A significant number of later may be as and, the predictive of the risk may be 12. Therefore, the first and most important is to out new, optimized large-scale studies with follow-up periods the of the initial prodromal phase, as in the CER study 18. The risk enrichment can also be advanced through the inclusion of following the of recent research on the prediction of through the cognitive impairment This condition a risk for with a conversion rate comparable to the risk for the patients certain imaging and the predictive risk enrichment may be possible for using brain but also impairments of and which are with the psychosis risk and are more and in cases with a later transition to schizophrenia and other new large-scale studies with sufficiently observation periods could whether the risk enrichment can be achieved by of such The of this strategy is on the progress of research on biological and environmental risk factors and their interactions, as is currently attempted in the Network of schizophrenia study In other medical disciplines, such as or a risk which does not in a of is using for multivariate clinical staging by risk In the of study, this approach was into psychosis prediction research for the first time A clinical model was developed based on a including six variables positive disturbances Assessment of in the past and years of Based on the individual a multivariate for further the risk of transition to psychosis into risk was each a increased relative risk to the general with each This model was argued to improve the prediction of psychosis by a of the individual risk in terms of and a more risk estimation or clinical staging of risk, in studies, could the development of risk adapted inclusion criteria for randomized preventive In the first application of this approach in the only clinical and variables were It remains to be whether a model including or environmental variables would increase the predictive accuracy even In studies have to whether such can also be applied to the prediction of psychosis within different time The currently ongoing of the has a about the inclusion of a risk for psychosis in to prevention initially argued this and to the that the application of as criteria could that the high rate of predictions in would be to increase up to in general This is and prior to whether to the in the of the The on the predictive of at risk criteria, thereby the persons meeting at risk criteria already from mental and functional for which they seek Moreover, they psychological and cognitive with and functional the majority of help-seeking at risk persons general criteria for mental disorder a clinically significant behavioral or psychological with disability and have to be considered as i.e. as people with the need and to be these in there are reasons for the inclusion of a clinical in the as by current at risk criteria, not as a prodromal risk for first psychosis, but as an to medical the of such an diagnosis would have the of the by the current mental state to a and Although an increased risk of psychosis would continue to be a of such a the psychological and medical focus would be from an to and At this current state of the criteria would be the for the inclusion of this A for the and of a new of international and studies would be with this inclusion in and later on also in A new prevention approach is by the of and studies a of the onset of psychosis the with the first results are for and The transition rate was lower in an group of UHR adolescents than in a group and this was at a an was evaluated in 10 patients in an pilot and a significant improvement in different was In an study, time was in an UHR group with as with a group suggesting a of This was the first study imaging data on effects in individuals at risk. The preventive of is currently in the process of in the Australian Prodrome study With the of schizophrenia is the first mental disorder to which the prediction and prevention program of modern medicine has been The results are and justify the that in the years to come it be possible to provide preventive strategies to the individual risk of of each In to a reduction in risk assessment has to be by neurobiological and psychosocial risk factors, and indicated prevention has to be further developed towards selective prevention. This a new of large sample studies for prediction as well as prevention, with observation In these studies, of risk selected to predictive must be psychological and pharmacological interventions need to be on a long-term basis, more prevention strategies have to be In to be to and such studies, it would be to mental states, as by the currently used risk symptoms, in the of the

World Psychiatry · 127 citationsread the source →

A social neuroscience perspective on clinical empathy

Clinical empathy is an important element of quality health care. Empathic communication is associated with improved patient satisfaction, increased adherence to treatment, and fewer malpractice complaints 1. Patients' perceptions of their physicians' empathy are positively related to more favorable health outcomes 2-4. In addition to improving patient outcomes, clinical empathy is associated with increased overall well-being for the physician 5. High levels of practitioner empathy have been associated with decreased burnout, personal distress, depression and anxiety, along with increased life satisfaction and psychological well-being 6, 7. Despite increasing appreciation of the value of empathy, medical educators continue to struggle with how best to educate students and residents on empathy maintenance. There have been several promising creative approaches that have shown demonstrable short-term success 8. However, there is a lack of evidence for enduring success, that is, for interventions during medical education that will enable physicians to sustain empathy throughout their careers. A more comprehensive and precise understanding of the subcomponents of empathy and how they are influenced by stress and anxiety is needed in order to design targeted interventions. Empathy is difficult to define, and an operational definition remains elusive. In medicine, empathy has often been conceptualized as consisting of two primary features: cognitive empathy, defined as the ability to recognize and understand another's experience, to communicate and confirm that understanding with the other person, and to take effective action to then act appropriately in a helpful manner 9, and affective empathy, defined as emotional resonance with the patient 10. Cognitive empathy has been singled out as beneficial in the clinical relationship, while affective empathy has been viewed as interfering with the physician's ability to make effective diagnoses and facilitate better outcomes. This has resulted in the teaching and practice of “detached concern”, a process where physicians establish a certain emotional distance from their patients in order to maintain objectivity and limit exposure to the negative emotions routinely experienced by those patients 11. However, recent research has demonstrated that the underlying rationale for implementing a “detached concern” approach is no longer tenable. First, affective engagement contributes to empathy, improving cognitive accuracy as well as affective understanding 12. Second, patients respond differently to emotionally engaged physicians. Patients who perceive their physicians as emotionally attuned or genuinely concerned disclose more, are more adherent to treatment, and show greater agency in addressing serious health problems such as cancer 11. Furthermore, there is now convincing empirical evidence that cognitive and affective aspects interact in the experience of empathy 13. Finally, the primary motivation behind the “detached concern” approach, that emotional connection will necessarily lead individuals into emotional turmoil, is not supported by the literature 14. Despite the clear importance of empathy in clinical settings, many physicians experience difficulty empathizing with their patients. For instance, a study which coded interviews between physicians and lung cancer patients found that, out of 384 empathic opportunities – defined as patients' statements including an explicit description of emotion or patients' statements or clues that indicated an underlying emotion – physicians responded empathically to only 39 (10%), most often reacting with little emotional support and shifting to biomedical questions and statements 15. Using patient-physician interaction videos where students are taught to identify and code these types of empathic opportunities, as well as what would be appropriate empathic responses, could help them more effectively address those opportunities. Additionally, sustaining empathy during distressing moments begins with doctors learning to take their own emotional temperatures, so that they can notice when they are anxious and take a deep breath or count to ten before responding to the patient. Both implementing mindfulness skills 16 and learning to return focus on the patient by becoming curious about what the patient is most concerned about at that moment can help physicians maintain empathy 11. Intensive training in mindful communication has been shown to reduce psychological distress and burnout, and increase empathy 17. The vast majority of individuals have the capacity for empathy, and research suggests that medical students start school with similar or higher levels of empathy compared to an age-matched control group 18. However, empathy significantly declines over the course of medical school 10. The precise underlying causes of this decline are not well understood, and multiple factors likely play a role. The decrease has been attributed to a curriculum that promotes the objectification of the patient 19, increasing workload, mistreatment by supervisors, and lack of emotional support 6, 20. High levels of burnout, personal distress, depression and anxiety have also been found to contribute to the erosion of empathy in medical school 7, 20. Notably, the decline in empathy is not consistent across students. A longitudinal study of 446 medical students found two distinct groups, with 70% showing a significant decline on the Jefferson Scale of Physician Empathy, and 30% seeming to have protective factors that neutralize the erosion of empathy 10. This study demonstrated that individuals in patient oriented specialties showed less decline in empathy than those in technology oriented specialties, and suggested that students with individual traits that protect against empathy erosion self-select into the more patient focused specialties 10. This could be the case, or it could be that training for patient focused areas places more emphasis on skills such as listening to the patient and how to counteract objectification of the patient, important to maintaining empathy in a patient-physician interaction. Additionally, greater perceived social support from faculty and greater satisfaction with the learning quality of the environment have been associated with increased resilience to burnout, and high levels of stress and fatigue have been associated with decreased resilience to burnout 21. As increased burnout has previously been associated with decreased empathy in medical students 22, it is possible that these protective factors might also contribute to maintaining empathy. Empathy is a natural socio-emotional competency that has evolved with the mammalian brain to form and maintain social bonds, and which encompasses different components 13. Affective sharing, the first element of empathy to appear during ontogeny, refers to the unconscious sharing of the affective state of another, which can be assessed by measures of concordance of skin conductance (an index of autonomic arousal) between two individuals 23. Empathic understanding entails the conscious awareness of the emotional state of another person. Empathic concern refers to a motivation to care for someone in need. Successful emotion regulation enables the control of emotion, drive and motivation in the service of adaptive behavior. Even though these components are intertwined and not independent of one another, it is helpful to consider them separately, as each contributes to various aspects of the experience of empathy, and could be the target of specific interventions to promote clinical empathy in medical students 24. Recent work in social neuroscience using functional neuroimaging demonstrates that the affective, cognitive and regulatory components of empathy involve interacting neural circuits 25. Empathic arousal is mediated by strong bidirectional connections between the brainstem, amygdala and sensory cortices, as well as connections with the hypothalamus, insula and somatosensory cortex 13, 24. The cognitive aspects of empathy, such as emotion understanding and emotion regulation, are closely related to processes involved in perspective taking, self-regulation, and executive attention subserved by the medial prefrontal cortex, dorsolateral prefrontal cortex and temporo-parietal junction. Finally, the ability to feel concern and care for others has deep evolutionary roots that likely evolved in the context of parental care 26. Its neural underpinnings are found in subcortical neural systems similar to those known to regulate maternal behavior, especially the hypothalamus and orbitofrontal cortex 27. These components differently contribute to the experience of clinical empathy. Affective sharing may act as a gain antecedent to empathic understanding, while cognitive components are important for representing the mental states of self and other, necessary to make decisions in a medical context 24. Importantly, the type of emotion regulation an individual employs largely determines whether cognitive resources are drained or primed 28. Specifically, research shows that a detached perspective can quickly dampen emotional reactions or filter out emotional information. This can be adaptive to a surgeon while operating on his anesthetized patient, but maladaptive when the same physician interacts with his patient after the surgery 28. This example illustrates the flexibility of emotion regulation in clinical settings, depending on both the physician's goals and the patient's needs. The perception of pain in others acts as an empathic signal, alerting individuals that another person is at risk, attracting their attention and motivating social behaviors. The neural response to the pain and distress of others, a situation familiar to physicians, has been used in social neuroscience research as a window into the neurobiological underpinnings of empathy. Several regions involved in the experience of physical pain, including the anterior cingulate cortex, insula, periaqueductal gray, orbitofrontal cortex and amygdala, are activated by the perception or even the imagination of another individual in pain 29. Importantly, the pattern of neural response is highly flexible and can be modulated by a number of contextual, cognitive, social and interpersonal factors 25. In the context of medicine, two neuroimaging experiments examined the neurophysiological response to the perception of pain in physicians 30, 31. Physicians as well as matched non-physician controls underwent functional magnetic resonance imaging while watching videos of needles being inserted into another person's body parts (face, hands and feet), as well as videos of the same areas being touched by a cotton bud 30. Physicians showed significantly less activation in brain areas involved in empathy for pain (anterior cingulate cortex, insula) than did non-physicians. In addition, physicians showed significantly greater activation in areas involved in executive control, self-regulation, and mental states understanding. These findings suggest less empathic arousal and greater cognitive regulation of an emotional response among the physicians, and indicate that physicians' down-regulation of the pain response dampens their negative arousal to the pain of others. This may have beneficial consequences by freeing up cognitive resources necessary for being of assistance and perhaps even for expressing empathic concern. These results may also inform individual differences in empathic decline and professional distress. Meta-analyses show that clinicians' distress is a key determinant of empathy decline 6. Medical students who are most vulnerable to professional distress, which may lead to emotional exhaustion, detachment and a low sense of accomplishment, may be those who have difficulties regulating their negative emotions. On the other hand, students with overly suppressed pain responses and insufficient negative arousal will also have problems with empathy. Some modicum empathic arousal (or affective sharing) may be necessary to help physicians attune to and empathically understand patients' emotions. A positive emotional reappraisal requires emotional content from the patient to be reinterpreted, molding potentially important information once it is available 28. Empathic disposition varies across individuals, and these differences are likely in part accounted for by interactions between an individual's life history, psychological traits and genetic makeup. Attachment is one construct, first proposed by Bowlby 32, which appears to reside at the interface of all three of these determinants. Attachment theory offers a compelling framework for understanding one's capacity to connect with others and develop supportive relationships as coping resources, and predicts individual differences in empathy 33. Security of attachment correlates with the individual degree of empathy and successful emotion regulation, and is inversely related to pain report and emotional distress 34. Empirical research also indicates that attachment security provides a foundation for empathic concern and caregiving 35. Importantly, these attachment styles are relatively stable across the lifespan. In recent years, a great deal of work has begun to reveal some of the underlying neuroanatomical and neurochemical foundations of attachment-related processes and the variance in such attributes both between and within species 36. Such research has identified a number of neuropeptides that are clearly involved in an array of attachment-related social behaviors, including opioids, vasopressin and oxytocin. Oxytocin, for example, has been demonstrated to play a central role in the initiation of maternal behaviors, social recognition and pair bonding in rodents 37. Studies in humans have demonstrated that oxytocin infusion can modulate a number of attachment-related behaviors, including trust, generosity, empathic concern, and empathic accuracy 38. Oxytocin administration selectively reduces emotional arousal to threatening social images 39 and differentially modulates visual attention toward social signals of positive approach 40. Moreover, it appears that individuals lacking high quality social connections show significantly reduced responses to oxytocin administration 39, which may reflect reduced receptor sensitivity. Research into the influence of genetic variation within the oxytocin receptor has provided converging evidence of the role that oxytocin plays in human social behavior. Polymorphisms within the oxytocin receptor have been shown to be related to affiliative behavior, behavioral and dispositional empathy, and perceived social connectedness 41. Similarly, genetic variation in the oxytocin receptor is related to decreased neuroendocrine and autonomic reactivity to social stress and interacts with perceived social support to dampen physiological reactivity to social-evaluative threat 41. Importantly, this does not suggest that empathy-related behaviors are genetically determined. Particular alleles in the oxytocin receptor system (or vasopressin or opioid systems) previously considered “vulnerability genes” can actually be viewed as “plasticity genes” in that they allow some individuals to be more sensitive to the social environment in general 42. This is consistent with the observation of large individual differences in what can be viewed as a “biological sensitivity to context”, in which people are especially interpersonally adept in socially supportive environments and especially anxious and withdrawn in noxious environments 43. A meta-analysis of studies that evaluated various contextual influences on patient outcomes found that physicians who adopted a reassuring warm and friendly approach were more effective than those employing detached concern 44. Empathic medical care may provide patients with a sense of personal connection and perceived control over their health that results in more effective coping strategies, influencing health outcomes through chronic modulation of physiological stress responses. In fact, a quarter century of research in neuroendocrinology and stress physiology has clearly demonstrated that the perception of social support and stressor controllability can have profound influences on the hormonal, cardiovascular and immunological response to a broad array of physiological responses in both humans and non-human animal models 45. Indeed, perceived controllability over a stressor is associated with prefrontal cortex mediated regulation of limbic (amygdala and hypothalamus) and brainstem (dorsal raphe nucleus) structures associated with neuroendocrine and autonomic nervous system reactivity 45. This provides a direct pathway through which the perception of one's ability to control aspects of his/her disease is capable of regulating physiological processes ranging from glucose metabolism and blood pressure to immunomodulation and neurogenesis 46. Physicians routinely present information to their patients capable of generating substantial physiological stress responses. In many such cases, the physician-patient relationship represents the front line in the battle against disease, as it has the potential to shape the endogenous responses to illness-related stress that, in some cases, can have effects similar to pharmacological interventions 3. Empathic concern, as opposed to detached concern, allows physicians to better understand their patients and modify their approach to fit the individuals they are attempting to treat. Given the past quarter century of work showing that quality emotional connection has comparable influences on health outcomes as obesity and hypertension 47, it is clear that empathic approaches are needed for patient care. The current view of empathy in clinical practice is limited and focused primarily on self-reports of physicians, with little understanding of the mechanisms which contribute to declining empathy during medical school and a lack of empathy generally within the medical field. A better scientific understanding of the connections between the mechanisms involved in interpersonal sensitivity, empathy, and care-giving behavior is needed to help physicians maintain high levels of empathy in clinical practice while limiting burnout and personal distress 48. This understanding should be incorporated into research on the organizational and contextual factors that shape medical professionalization. It is now possible to bring to the study of clinical empathy a risk-vulnerability approach that promises to be both more precise and more comprehensive than previous research. This approach will increase our capacity to design better institutions and educational interventions to support empathy within clinical practice and to protect against its decline. Some interventions to improve empathy and communication between physicians and patients have already shown positive effects on both physicians' professional satisfaction and well-being. There is a need, however, for dedicated research to respond to the vital call for empathy enhancement in medicine with programs using social neuroscience-based knowledge. The writing of this paper was supported by grants from the John Templeton Foundation (The Science of Philanthropy Initiative and Wisdom Research at the University of Chicago) and from National Institutes of Health (R01MH087525; R01MH084934) to J. Decety.

World Psychiatry · 97 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 →

Admissions to acute adolescent psychiatric units: a prospective study of clinical severity and outcome.

Background: Several countries have established or are planning acute psychiatric in-patient services that accept around-the-clock emergency admission of adolescents. Our aim was to investigate the characteristics and clinical outcomes of a cohort of patients at four Norwegian units. Methods: We used a prospective pre-post observational design. Four units implemented a clinician-rated outcome measure, the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA), which measures mental health problems and their severity. We collected also data about the diagnoses, suicidal problems, family situations, and the involvement of the Child Protection Service. Predictions of outcome (change in HoNOSCA total score) were analysed with a regression model. Results: The sample comprised 192 adolescents admitted during one year (response rate 87%). Mean age was 15.7 years (range 10-18) and 70% were girls. Fifty-eight per cent had suicidal problems at intake and the mean intake HoNOSCA total score was 18.5 (SD 6.4). The largest groups of main diagnostic conditions were affective (28%) and externalizing (26%) disorders. Diagnoses and other patient characteristics at intake did not differ between units. Clinical psychiatric disorders and developmental disorders were associated with severity (on HoNOSCA) at intake but not with outcome. Of adolescents ≥ 16 years, 33% were compulsorily admitted. Median length of stay was 8.5 days and 75% of patients stayed less than a month. Compulsory admissions and length of stay varied between units. Mean change (improvement) in the HoNOSCA total score was 5.1 (SD 6.2), with considerable variation between units. Mean discharge score was close to the often-reported outpatient level, and self-injury and emotional symptoms were the most reduced symptoms during the stay. In a regression model, unit, high HoNOSCA total score at intake, or involvement of the Child Protection Service predicted improvement during admission. Conclusions: Acute psychiatric in-patient units for adolescents effectively meet important needs for young people with suicidal risks or other severe mental health problems. These units may act in suicide prevention, stabilizing symptom severity at a lower level within a short stay. It is important to explore the differences in outcome, compulsory admissions, and length of stay between units.

International journal of mental health systems · 41 citationsread the source →