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Peer-reviewed works with DOI and abstract, discovered from MEDLINE-indexed literature. Candidates: no tier, no stated finding, not yet read.

George R, Jeba J, Ramkumar G, Chacko AG, Tharyan P. (2015)MEDLINE-indexed journal, not yet read by usThe Cochrane database of systematic reviews · meta-analysis

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

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 We also contacted experts for relevant published, unpublished and ongoing trials.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

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

Applebaum AJ, Baser RE, Roberts KE, Lynch K, Gebert R, Breitbart WS, Diamond EL. (2022)MEDLINE-indexed journal, not yet read by usTranslational behavioral medicine · randomised controlled trial

Meaning-Centered Psychotherapy for Cancer Caregivers: A pilot trial among caregivers of patients with glioblastoma multiforme.

Caregivers of patients with glioblastoma multiforme (GBM) are at significant risk for existential distress. Such distress negatively impacts caregivers' quality of life and capacity to serve in their role as healthcare proxies, and ultimately, contributes to poor bereavement outcomes. Our team developed Meaning-Centered Psychotherapy for Cancer Caregivers (MCP-C), the first targeted psychosocial intervention that directly addresses existential distress in caregivers. The purpose of this study was to evaluate the feasibility, acceptability, and preliminary effects of MCP-C among caregivers of patients with GBM via a mixed-method pilot trial. Caregivers were randomized to seven sessions of MCP-C or Enhanced Usual Care (EUC), which included distress screening and the provision of targeted referrals and completed quantitative assessments at baseline (T1), after completion of MCP-C (T2), and at 2-month follow-up (T3). A subset of participants engaged in semistructured interviews at T2. Of 60 caregivers randomized, 55 were evaluable for preliminary efficacy analysis. Constrained linear mixed models indicated the MCP-C arm had statistically significant improvement relative to the EUC arm in the primary outcome of personal meaning and multiple secondary outcomes, including benefit finding, depressive symptomatology, and spiritual wellbeing. MCP-C demonstrated preliminary efficacy in facilitating caregivers' capacity to experience a sense of meaning and purpose despite the challenges and suffering associated with providing care to patients with GBM. Future studies are needed among more diverse samples of caregivers and should include the opportunity for concurrent patient enrollment to allow for a reciprocal and augmented experience of meaning among patient-caregiver dyads.

Translational behavioral medicine · randomised controlled trial · 28 citationsread the source →

Effect of a high-fat Mediterranean diet on bodyweight and waist circumference: a prespecified secondary outcomes analysis of the PREDIMED randomised controlled trial.

Background: Because of the high density of fat, high-fat diets are perceived as likely to lead to increased bodyweight, hence health-care providers are reluctant to recommend them to overweight or obese individuals. We assessed the long-term effects of ad libitum, high-fat, high-vegetable-fat Mediterranean diets on bodyweight and waist circumference in older people at risk of cardiovascular disease, most of whom were overweight or obese. Methods: PREDIMED was a 5 year parallel-group, multicentre, randomised, controlled clinical trial done in primary care centres affiliated to 11 hospitals in Spain. 7447 asymptomatic men (aged 55-80 years) and women (aged 60-80 years) who had type 2 diabetes or three or more cardiovascular risk factors were randomly assigned (1:1:1) with a computer-generated number sequence to one of three interventions: Mediterranean diet supplemented with extra-virgin olive oil (n=2543); Mediterranean diet supplemented with nuts (n=2454); or a control diet (advice to reduce dietary fat; n=2450). Energy restriction was not advised, nor was physical activity promoted. In 2016, we reported the 5 year changes in bodyweight and waist circumference, but because of a subsequently identified protocol deviation (including enrolment of household members without randomisation, assignment to a study group without randomisation of some participants at one of 11 study sites, and apparent inconsistent use of randomisation tables at another site; 866 [11·6%] participants were affected in total), we have withdrawn our previously published report and now report revised effect estimates based on reanalyses that do not rely exclusively on the assumption that all the participants were randomly assigned. In this analysis of the trial, we measured bodyweight and waist circumference at baseline and yearly for 5 years in the intention-to-treat population. The PREDIMED trial is registered with ISRCTN.com, number ISRCTN35739639. Findings: After a median 4·8 years (IQR 2·8-5·8) of follow-up, participants in all three groups had marginally reduced bodyweight and increased waist circumference. After multivariable adjustment, including adjustment for propensity scores and use of robust variance estimators, the difference in 5 year changes in bodyweight in the Mediterranean diet with olive oil group was -0·410 kg (95% CI -0·830 to 0·010; p=0·056) and in the nut group was -0·016 kg (-0·453 to 0·421; p=0·942), compared with the control group. The adjusted difference in 5 year changes in waist circumference was -0·466 cm (-1·109 to 0·176; p=0·154) in the Mediterranean diet with olive oil group and -0·923 cm (-1·604 to -0·241; p=0·008) in the nut group, compared with the control group. Interpretation: A long-term intervention with an unrestricted-calorie, high-vegetable-fat Mediterranean diet was associated with no significant difference in bodyweight and some evidence of less gain in central adiposity compared with a control diet. These results lend support to advice not restricting intake of healthy fats for bodyweight maintenance. Funding: Spanish Government, CIBERobn, Instituto de Salud Carlos III, Hojiblanca, Patrimonio Comunal Olivarero, California Walnut Commission, Borges SA, and Morella Nuts.

The lancet. Diabetes & endocrinology · randomised controlled trial · 101 citationsread the source →

Arora M, Nazar GP, Gupta VK, Perry CL, Reddy KS, Stigler MH. (2012)MEDLINE-indexed journal, not yet read by usBMC public health · randomised controlled trial

Association of breakfast intake with obesity, dietary and physical activity behavior among urban school-aged adolescents in Delhi, India: results of a cross-sectional study.

Background: In developed countries, regular breakfast consumption is inversely associated with excess weight and directly associated with better dietary and improved physical activity behaviors. Our objective was to describe the frequency of breakfast consumption among school-going adolescents in Delhi and evaluate its association with overweight and obesity as well as other dietary, physical activity, and sedentary behaviors. Methods: Design: Cross-sectional study. Setting: Eight schools (Private and Government) of Delhi in the year 2006. Participants: 1814 students from 8th and 10th grades; response rate was 87.2%; 55% were 8th graders, 60% were boys and 52% attended Private schools. Main outcome measures: Body mass index, self-reported breakfast consumption, diet and physical activity related behaviors, and psychosocial factors. Data analysis: Mixed effects regression models were employed, adjusting for age, gender, grade level and school type (SES). Results: Significantly more Government school (lower SES) students consumed breakfast daily as compared to Private school (higher SES) students (73.8% vs. 66.3%; p<0.01). More 8th graders consumed breakfast daily vs.10th graders (72.3% vs. 67.0%; p<0.05). A dose-response relationship was observed such that overall prevalence of overweight and obesity among adolescents who consumed breakfast daily (14.6%) was significantly lower vs. those who only sometimes (15.2%) or never (22.9%) consumed breakfast (p<0.05 for trend). This relationship was statistically significant for boys (15.4 % vs. 16.5% vs. 26.0; p<0.05 for trend) but not for girls. Intake of dairy products, fruits and vegetables was 5.5 (95% CI 2.4-12.5), 1.7 (95% CI 1.1-2.5) and 2.2 (95% CI 1.3-3.5) times higher among those who consumed breakfast daily vs. those who never consumed breakfast. Breakfast consumption was associated with greater physical activity vs. those who never consumed breakfast. Positive values and beliefs about healthy eating; body image satisfaction; and positive peer and parental influence were positively associated with daily breakfast consumption, while depression was negatively associated. Conclusion: Daily breakfast consumption is associated with less overweight and obesity and with healthier dietary- and physical activity-related behaviors among urban Indian students. Although prospective studies should confirm the present results, intervention programs to prevent or treat childhood obesity in India should consider emphasizing regular breakfast consumption.

BMC public health · randomised controlled trial · 50 citationsread the source →

Parkes A, Green M, Mitchell K. (2019)MEDLINE-indexed journal, not yet read by usJournal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) · cohort or longitudinal

Coparenting and parenting pathways from the couple relationship to children's behavior problems.

Although an extensive literature has linked couple conflict with the development of children's externalizing behavior problems, longer term protective effects of positive dimensions of couple relationships on children's externalizing behavior remain understudied, particularly in relation to underlying mechanisms. Supportiveness in the dyadic couple relationship may enhance mothers' and fathers' individual parenting skills and protect against children's behavior problems, but the contribution of coparenting (couples' support for one another's individual parenting) remains unclear. This observational study investigated associations between couple supportiveness in children's infancy and middle childhood externalizing problems, exploring pathways involving coparenting and/or mothers' and fathers' individual parenting using data from the U.K. Millennium Cohort Study (MCS; N = 5,779) and the U.S. Fragile Families and Child Wellbeing Study (FFS; N = 2,069). Couple supportiveness was associated with reduced externalizing problems 8 to 10 years later (standardized betas: MCS = -.13, FFS = -.11, both ps < .001). Much of this effect (60% MCS, 55% FFS) was attributable to coparenting and parenting when children were aged 3 to 5 years. Pathways from couple supportiveness involving negative parenting were stronger than those via positive parenting, pathways via mothers' parenting were stronger than those via fathers' parenting, and there were pathways via coparenting alone (without affecting parenting). Pathways involving coparenting were similar in magnitude (MCS), or larger (FFS), than those involving parenting alone. Consistent findings across different population samples suggest that helping parents to support one another in coparenting and to develop their individual parenting skills may lessen the longer term impact of couple relationship problems during early childhood. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) · cohort or longitudinal · 30 citationsread the source →

Road traffic noise is associated with increased cardiovascular morbidity and mortality and all-cause mortality in London.

Aims: Road traffic noise has been associated with hypertension but evidence for the long-term effects on hospital admissions and mortality is limited. We examined the effects of long-term exposure to road traffic noise on hospital admissions and mortality in the general population. Methods and results: The study population consisted of 8.6 million inhabitants of London, one of Europe's largest cities. We assessed small-area-level associations of day- (7:00-22:59) and nighttime (23:00-06:59) road traffic noise with cardiovascular hospital admissions and all-cause and cardiovascular mortality in all adults (≥25 years) and elderly (≥75 years) through Poisson regression models. We adjusted models for age, sex, area-level socioeconomic deprivation, ethnicity, smoking, air pollution, and neighbourhood spatial structure. Median daytime exposure to road traffic noise was 55.6 dB. Daytime road traffic noise increased the risk of hospital admission for stroke with relative risk (RR) 1.05 [95% confidence interval (CI): 1.02-1.09] in adults, and 1.09 (95% CI: 1.04-1.14) in the elderly in areas >60 vs. <55 dB. Nighttime noise was associated with stroke admissions only among the elderly. Daytime noise was significantly associated with all-cause mortality in adults [RR 1.04 (95% CI: 1.00-1.07) in areas >60 vs. <55 dB]. Positive but non-significant associations were seen with mortality for cardiovascular and ischaemic heart disease, and stroke. Results were similar for the elderly. Conclusions: Long-term exposure to road traffic noise was associated with small increased risks of all-cause mortality and cardiovascular mortality and morbidity in the general population, particularly for stroke in the elderly.

European heart journal · 125 citationsread the source →

Archie S, Rush BR, Akhtar-Danesh N, Norman R, Malla A, Roy P, Zipursky RB. (2007)MEDLINE-indexed journal, not yet read by usSchizophrenia bulletin · cohort or longitudinal

Substance use and abuse in first-episode psychosis: prevalence before and after early intervention.

Unlabelled: Despite the high prevalence of substance abuse among first-episode psychosis (FEP) populations, few studies examine whether early intervention (EI) improves substance abuse. Objective: To examine the prevalence and pattern of substance use and abuse among an FEP sample over 12 months. Methods: All the participants were diagnosed with a first episode of a schizophrenia spectrum disorder. The participants were followed prospectively. The prevalence rates of substance use and abuse from this sample were compared before and after 12 months of EI services and were compared with rates observed in a sample from the general population. Results: A total of 200 participants (80.0% males; mean age 24 years) entered the study: 183 participants completed all the assessments at baseline, 131 participants completed all the assessments at 12 months. At baseline, the findings showed similar prevalence rates between the FEP sample and the general sample for lifetime cannabis use (60% vs 55%, respectively) and hazardous alcohol use (26% vs 21%) but significantly different prevalence rates for lifetime hallucinogen (29% vs 15%; P < .001) and cocaine use (20% vs 14%; P < .001). At 12 months, the prevalence rates for drug abuse (P < .01), hazardous alcohol use (P < .01), and concurrent drug abuse and hazardous alcohol use (P < .05) were significantly lower than at baseline. Conclusion: Substance use and abuse decreased significantly after 12 months of EI services; EI services may be able to detect and to reduce substance use among FEP patients before it becomes a more serious disorder.

Schizophrenia bulletin · cohort or longitudinal · 74 citationsread the source →

Raina R, Agarwal A, Ausmundson S, Lakin M, Nandipati KC, Montague DK, Mansour D, Zippe CD. (2006)MEDLINE-indexed journal, not yet read by usInternational journal of impotence research · randomised controlled trial

Early use of vacuum constriction device following radical prostatectomy facilitates early sexual activity and potentially earlier return of erectile function.

To assess the efficacy of vacuum constriction devices (VCD) following radical prostatectomy (RP) and determine whether early use of VCD facilitates early sexual activity and potentially earlier return of erectile function. This prospective study consisted of 109 patients who underwent nerve-sparing (NS) or non-nerve-sparing (NNS) RP between August 1999 and October 2001 and developed erectile dysfunction following surgery. The patients were randomized to VCD use daily for 9 months (Group 1, N=74) or observation without any erectogenic treatment (Group 2, N=35). Treatment efficacy was analyzed by responses to the Sexual Health Inventory of Men (SHIM) (abridged 5-item International Index of Erectile Function (IIEF-5)), which were stratified by the NS status. Patient outcome regarding compliance, change in penile length, return of natural erection, and ability for vaginal intercourse were also assessed. The mean patient age was 58.2 years, and the minimum follow-up was 9 months. Use of VCD began at an average of 3.9 weeks after RP. In Group 1, 80% (60/74) successfully used their VCD with a constriction ring for vaginal intercourse at a frequency of twice/week with an overall spousal satisfaction rate of 55% (33/60). In all, 19 of these 60 patients (32%) reported return of natural erections at 9 months, with 10/60 (17%) having erections sufficient for vaginal intercourse. The abridged IIEF-5 score significantly increased after VCD use in both the NS and NNS groups. After a mean use of 3 months, 14/74 (18%) discontinued treatment. In Group 2, 37% (13/35) of patients regained spontaneous erections at a minimum follow-up of 9 months after surgery. However, only four of these patients (29%) had erections sufficient for successful vaginal intercourse and rest of patients (71%) sought adjuvant treatment. Of the 60 successful users, 14 (23%) reported a decrease in penile length and circumference at 9 months (range, 4-8 months) compared to 12/14 (85%) among the nonresponders. However, in control group 22/35 reported decrease in penile length and circumference. Early use of VCD following RP facilitates early sexual intercourse, early patient/spousal sexual satisfaction, and potentially an earlier return of natural erections sufficient for vaginal penetration.

International journal of impotence research · randomised controlled trial · 131 citationsread the source →

Mediterranean dietary pattern and depression: the PREDIMED randomized trial.

Background: A few observational studies have found an inverse association between adherence to a Mediterranean diet and the risk of depression. Randomized trials with an intervention based on this dietary pattern could provide the most definitive answer to the findings reported by observational studies. The aim of this study was to compare in a randomized trial the effects of two Mediterranean diets versus a low-fat diet on depression risk after at least 3 years of intervention. Methods: This was a multicenter, randomized, primary prevention field trial of cardiovascular disease (Prevención con Dieta Mediterránea (PREDIMED Study)) based on community-dwelling men aged 55 to 80 years and women aged 60 to 80 years at high risk of cardiovascular disease (51% of them had type 2 diabetes; DM2) attending primary care centers affiliated with 11 Spanish teaching hospitals. Primary analyses were performed on an intention-to-treat basis. Cox regression models were used to assess the relationship between the nutritional intervention groups and the incidence of depression. Results: We identified 224 new cases of depression during follow-up. There was an inverse association with depression for participants assigned to a Mediterranean diet supplemented with nuts (multivariate hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.55 to 1.10) compared with participants assigned to the control group, although this was not significant. However, when the analysis was restricted to participants with DM2, the magnitude of the effect of the intervention with the Mediterranean diet supplemented with nuts did reach statistical significance (multivariate HR = 0.59; 95% CI 0.36 to 0.98). Conclusions: The result suggest that a Mediterranean diet supplemented with nuts could exert a beneficial effect on the risk of depression in patients with DM2. Trial registration: This trial has been registered in the Current Controlled Trials with the number ISRCTN 35739639.

BMC medicine · randomised controlled trial · 213 citationsread the source →

Oscar A. Carretero; Suzanne Oparil (2000)MEDLINE-indexed journal, not yet read by usCirculation · review

Essential Hypertension

HomeCirculationVol. 101, No. 3Essential Hypertension Free AccessOtherPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessOtherPDF/EPUBEssential Hypertension Part I: Definition and Etiology Oscar A. Carretero and Suzanne Oparil Oscar A. CarreteroOscar A. Carretero From the Hypertension and Vascular Research Division, Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich (O.A.C.), and the Division of Cardiovascular Disease, Vascular Biology and Hypertension Program, University of Alabama School of Medicine, Birmingham (S.O.). and Suzanne OparilSuzanne Oparil From the Hypertension and Vascular Research Division, Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich (O.A.C.), and the Division of Cardiovascular Disease, Vascular Biology and Hypertension Program, University of Alabama School of Medicine, Birmingham (S.O.). Originally published25 Jan 2000https://doi.org/10.1161/01.CIR.101.3.329Circulation. 2000;101:329–335Essential hypertension remains a major modifiable risk factor for cardiovascular disease (CVD) despite important advances in our understanding of its pathophysiology and the availability of effective treatment strategies. High blood pressure (BP) increases the risk of CVD for millions of people worldwide, and there is evidence that the problem is only getting worse. In the past decade, age-adjusted rates of stroke incidence have risen, and the slope of the age-adjusted rate of decline in coronary disease has leveled off. The incidence of end-stage renal disease and the prevalence of heart failure have also increased. A major contributor to these trends is inadequate control of BP in the hypertensive population. This review of current concepts regarding the definition, etiology, and treatment of essential hypertension is intended to aid the clinician in identifying those individuals at high risk who need to undergo evaluation and treatment, as well as in selecting optimal treatment strategies for hypertensive patients with comorbid conditions and/or target organ damage. The part of the review that deals with the genetic basis of hypertension and the gene/environment interaction that may lead to elevated BP is still a work in progress. Information gained from the Human Genome Project and from ongoing studies of the genetic basis of hypertension both in animal models and human populations may revolutionize the treatment of hypertension by replacing current empirical therapy with more effective, targeted treatments based on the genotype of the patient. Concepts introduced in this review form the basis for such "pharmacogenomic" approaches to antihypertensive therapy. Definition of Essential or Primary HypertensionBP is a quantitative trait that is highly variable1 ; in population studies, BP has a normal distribution that is slightly skewed to the right. There is a strong positive and continuous correlation between BP and the risk of CVD (stroke, myocardial infarction, heart failure), renal disease, and mortality, even in the normotensive range. This correlation is more robust with systolic than with diastolic BP.2 There is no specific level of BP where cardiovascular and renal complications start to occur; thus the definition of hypertension is arbitrary but needed for practical reasons in patient assessment and treatment. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) defined and classified hypertension in adults, as shown in Table 1.3 The diagnosis of hypertension is made when the average of 2 or more diastolic BP measurements on at least 2 subsequent visits is ≥90 mm Hg or when the average of multiple systolic BP readings on 2 or more subsequent visits is consistently ≥140 mm Hg. Isolated systolic hypertension is defined as systolic BP ≥140 mm Hg and diastolic BP <90 mm Hg. Individuals with high normal BP tend to maintain pressures that are above average for the general population and are at greater risk for development of definite hypertension and cardiovascular events than the general population. With the use of these definitions, it is estimated that 43 million people in the United States have hypertension or are taking antihypertensive medication, which is ≈24% of the adult population. This proportion changes with (1) race, being higher in blacks (32.4%) and lower in whites (23.3%) and Mexican Americans (22.6%); (2) age, because in industrialized countries systolic BP rises throughout life, whereas diastolic BP rises until age 55 to 60 years and thus the greater increase in prevalence of hypertension among the elderly is mainly due to systolic hypertension; (3) geographic patterns, because hypertension is more prevalent in the southeastern United States; (4) gender, because hypertension is more prevalent in men (though menopause tends to abolish this difference); and (5) socioeconomic status, which is an indicator of lifestyle attributes and is inversely related to the prevalence, morbidity, and mortality rates of hypertension. Essential, primary, or idiopathic hypertension is defined as high BP in which secondary causes such as renovascular disease, renal failure, pheochromocytoma, aldosteronism, or other causes of secondary hypertension or mendelian forms (monogenic) are not present. Essential hypertension accounts for 95% of all cases of hypertension. Essential hypertension is a heterogeneous disorder, with different patients having different causal factors that lead to high BP. Essential hypertension needs to be separated into various syndromes because the causes of high BP in most patients presently classified as having essential hypertension can be recognized. Known Etiological Factors in Essential HypertensionAlthough it has frequently been indicated that the causes of essential hypertension are not known, this is only partially true because we have little information on genetic variations or genes that are overexpressed or underexpressed as well as the intermediary phenotypes that they regulate to cause high BP.4 A number of factors increase BP, including (1) obesity, (2) insulin resistance, (3) high alcohol intake, (4) high salt intake (in salt-sensitive patients), (5) aging and perhaps (6) sedentary lifestyle, (7) stress, (8) low potassium intake, and (9) low calcium intake.56 Furthermore, many of these factors are additive, such as obesity and alcohol intake. In this review, variations in BP that are genetically determined will be called "inherited BP," although we do not know which genes cause BP to vary; we know from family studies that inherited BP can range from low normal BP to severe hypertension. Factors that increase BP, such as obesity and high alcohol and salt intake, will be called "hyperten-sinogenic factors." Some of these factors have inherited, behavioral, and environmental components. Inherited BP could be considered core BP, whereas hypertensinogenic factors cause BP to increase above the range of inherited BPs, thus creating 4 main possibilities: (1) patients who have inherited BP in the optimal category (<120/<80 mm Hg); if 1 or more hypertensinogenic factors are added, BP would probably increase but remain in the normal range (<135/<85 mm Hg) (Figure 1, first 2 columns); (2) patients who have inherited BP in the normal category (≤130/≤85 mm Hg); if 1 or more hypertensinogenic factors are added, BP will probably increase to the high normal range (130 to 139/85 to 89 mm Hg) or to stage 1 of the hypertensive category (140 to 159/90 to 99 mm Hg) (Figure 1, second 2 columns); (3) patients who have inherited BP in the high normal category (130 to 139/85 to 89 mm Hg); if 1 or more hypertensinogenic factors are added, BP will increase to the hypertensive range (≥140/≥90 mm Hg) (Figure 1, third 2 columns); and (4) patients who have inherited BP in the hypertensive range; addition of 1 or more hypertensinogenic factors will make hypertension more severe, changing it from stage 1 to stage 2 or 3 (Figure 1, fourth to sixth 2 columns).Theoretically, in a population unaffected by hypertensinogenic factors, BP will have a normal distribution; it will be skewed to the right and will have a narrow base or less variance (Figure 2, continuous line). When 1 hypertensinogenic factor is added to this population, such as increased body mass, one would expect the normal distribution curve to be further skewed to the right; consequently the base will be wider (more variance) and the curve will be flatter (Figure 2, broken line). If a second hypertensinogenic factor such as alcohol intake is added to increased body mass, the curve will be skewed more to the right and the variance will increase further, with more subjects classified as hypertensive (Figure 2, dotted line).Discovering which genetic variations place BP on the left or right side of the distribution curve is of both theoretical and practical importance because it could help the physician to better treat or cure hypertension.7 Recognition of the hypertensinogenic factors may allow nonpharmacological prevention, treatment, or cure of hypertension. Hypertensinogenic factors such as obesity, insulin resistance, or high alcohol intake also have an important genetic component. Furthermore, there are interactions between genetic and environmental factors (Figure 2) that influence intermediary phenotypes such as sympathetic nerve activity, the renin-angiotensin-aldosterone and renal kallikrein-kinin systems, and endothelial factors, which in turn influence other intermediary phenotypes such as sodium excretion, vascular reactivity, and cardiac contractility. These and many other intermediary phenotypes determine total vascular resistance and cardiac output and, consequently, BP. Recognition of the hypertensinogenic factor(s) and establishing that the patient's hypertension is the result of obesity (either alone or combined with other factors such as insulin resistance or high alcohol intake) or old age instead of essential hypertension may help the physician as well as the patient and his or her family to modify or eliminate these hypertensinogenic and CVD risk factors when possible, which may cure the hypertension or at least facilitate control of BP. When the hypertensinogenic factor cannot be reduced or eliminated, as with systolic hypertension induced by aging (arteriosclerosis), recognition of the underlying cause of high BP will emphasize the need for (1) further studies to determine whether the patient has arteriosclerosis and/or atherosclerosis, the magnitude of the disease, and whether there are occlusive lesions; (2) treatment of the atherosclerosis with lifestyle and dietary changes and lipid-lowering agents if necessary; and (3) pharmacological treatment of systolic hypertension to decrease passive stiffness (arteriosclerosis) of the major central elastic arteries and decrease morbidity and mortality rates. Thus recognition of factors that induce hypertension is not only of theoretical but also of practical importance. In conclusion, as stated by Beilin,8 "it is no longer appropriate to define essential hypertension as a rise in blood pressure without cause," since a number of causes can be clearly identified in most cases of so-called "essential hypertension." As discussed later in more detail, there is clear evidence that changes in lifestyle, including dietary changes that reduce body weight, fat, and alcohol intake and increase potassium and calcium intake,9 as well as exercise,1011 reduce or normalize BP in many patients. Inherited BPThe identification of variant (allelic) genes that contribute to the development of hypertension is complicated by the fact that the 2 phenotypes that determine BP, cardiac output and total peripheral resistance, are controlled by intermediary phenotypes, including the autonomic nervous system, vasopressor/vasodepressor hormones, the structure of the cardiovascular system, body fluid volume and renal function, and many others. Furthermore, these intermediary phenotypes are also controlled by complex mechanisms including BP itself.12 Thus there are many genes that could participate in the development of hypertension. The influence of genes on BP has been suggested by family studies demonstrating associations of BP among siblings and between parents and children. There is a better association among BP values in biological children than in adopted children and in identical as opposed to nonidentical twins. BP variability attributed to all genetic factors varies from 25% in pedigree studies to 65% in twin studies. Furthermore, genetic factors also influence behavioral patterns, which might lead to BP elevation. For example, a tendency toward obesity or alcoholism will be influenced by both genetic and environmental factors; thus the proportion of BP variability caused by inheritance is difficult to determine and may vary in different populations. Mutations in at least 10 genes have been shown to raise or lower BP through a common pathway by increasing or decreasing salt and water reabsorption by the nephron.1314 The genetic mutations responsible for 3 rare forms of mendelian (monogenic) hypertensive syndromes−glucocorticoid-remediable aldosteronism (GRA), Liddle's syndrome, and apparent mineralocorticoid excess−have been identified, whereas in a fourth, autosomal dominant hypertension with brachydactyly, the gene is not yet identified but has been mapped to chromosome 12 (12p). Subtle variations in one of these genes may also cause some forms of "essential" hypertension. For a review of the mutations that cause a decrease in BP, see Lifton.13Glucocorticoid-Remediable AldosteronismThis is an autosomal dominant form of monogenic hypertension in which aldosterone secretion is regulated by adrenocorticotropic hormone. Glucocorticoid treatment causes BP to decrease and gives the syndrome its name. The genetic mutation that causes GRA has been identified by Lifton14 as a chimeric gene fusing nucleotide sequences of the promoter-regulatory region of 11β-hydroxylase (controlled by adrenocorticotropic hormone) and the structural portion of the aldosterone synthase gene. The chimeric gene results from a meiotic mismatch and unequal crossing over. The patients are usually thought to have primary aldosteronism because they exhibit volume expansion, metabolic alkalosis with hypokalemia, low plasma renin, and high aldosterone. Most of the patients first described as having GRA showed severe hypertension and died prematurely from stroke. However, with the development of direct genetic testing, the BP of patients with this syndrome was found to cover a wide range, including normotensive levels.1516 In patients with GRA and normal BP, expression of the chimeric gene may be variable, but because steroid levels are similar in patients with severe and mild hypertension, this seems unlikely. It is also possible that the genetic background of the trait (other than the chimeric mutation), such as high renal kallikrein, places the inherited BP of these subjects in the low or ideal normal range and the mutation causes BP to increase to high normal or hypertensive stage 1. Thus the final BP would be the combined result of the inherited BP (including the genetic mutation) and the increase in BP caused by hypertensinogenic factors such as salt. Liddle's SyndromeThis is an autosomal dominant form of monogenic hypertension that results from mutations in the amiloride-sensitive epithelial sodium channel, leading to increased channel activity.17 The mutations reported to date result in the elimination of 45 to 75 amino acids from the cytoplasmic carboxyl terminus of β- or γ-subunits of the channel; thus Liddle's syndrome is genetically heterogeneous. It is characterized by the early onset of hypertension with hypokalemia and suppression of both plasma renin activity and aldosterone, the latter differentiating this syndrome from primary aldosteronism. Both the hypertension and the hypokalemia vary in severity, raising the possibility that some patients classified as having salt-sensitive essential hypertension actually have Liddle's syndrome.18 It is also possible that high BP in blacks, who are frequently salt-sensitive, is due to a polymorphism in one of the sodium channel genes or in one of the genes of systems that regulate it, causing its activity to increase. Apparent Mineralocorticoid ExcessThis is an autosomal recessive form of monogenic juvenile hypertension that results from a mutation in the renal-specific isoform 11β-hydroxysteroid dehydrogenase gene.19 Normally this enzyme converts cortisol to the inactive metabolite cortisone. In the distal nephron this is important because cortisol and aldosterone have a similar affinity for the mineralocorticoid receptor. The enzymatic deficiency allows the mineralocorticoid receptors in the nephron to be occupied and activated by cortisol, causing sodium and water retention, volume expansion, low renin, low aldosterone, and more importantly, a salt-sensitive form of hypertension. Thus this gene may be a locus for salt-sensitive essential hypertension. Autosomal Dominant Hypertension With BrachydactylyIn this monogenic syndrome, hypertension and brachydactyly are always inherited together (100% cosegregation).4 Affected persons are shorter than nonaffected relatives. The gene for hypertension has been mapped to the short arm of chromosome 12 (12p) in a large Turkish kindred. Two other families with this syndrome have been reported, 1 in Canada and 1 in the United States. In addition, the study of a Japanese child with hypertension and type E brachydactyly has allowed the area on 12p containing the gene mutation to be pinpointed further, although the gene responsible for this syndrome has not yet been cloned. Unlike the other 3 autosomal forms of hypertension, BP is not affected by volume expansion and the underlying mechanism is not known. Thus identification of the gene responsible may help clarify some of the genetic alterations in essential hypertension. Essential or Primary HypertensionThe genetic alterations responsible for inherited "essential" hypertension remain largely unknown.4 Results from family studies suggest several possible intermediary phenotypes (genetic traits) that may be related to inherited high BP, such as high sodium-lithium countertransport, low urinary kallikrein excretion, high fasting plasma insulin concentrations, high-density LDL subfractions, fat pattern index, and body mass index (BMI).12 Jeunemaitre et al2021 first reported a polymorphism in the angiotensinogen gene linked with essential hypertension in hypertensive siblings from Utah and France. This polymorphism consists of a substitution of thymidine for cytosine in nucleotide 704, which causes substitution of methionine for threonine at position 235 (M235T) and is associated with increased concentrations of plasma angiotensinogen. This variant appears to be in tight linkage disequilibrium with a promoter mutation in which adenine replaces guanine (-6A) upstream from the initiation side of transcription.22 Tests of promoter activity suggest that this nucleotide substitution increases the rate of gene transcription, which may explain the higher angiotensinogen concentration found in subjects with the variant M235T.22 Many studies have been published on various racial groups with regard to the association between allelic variations in angiotensinogen and hypertension.23 However, these variations explain only a small part of the BP variation (≈6%). Furthermore, plasma angiotensinogen concentrations, though higher in patients with the polymorphism, clearly overlap with normotensive patients. Polymorphisms and mutations in other genes such as angiotensin-converting enzyme, β2-adrenergic receptor, α-adducin, angiotensinase C, renin-binding protein, G-protein β3-subunit, atrial natriuretic factor, and the insulin receptor have also been linked to the development of essential hypertension; however, most of them show a weak association if any, and most of these studies need further confirmation. Thus these gene alterations will not be discussed here because they go beyond the scope of this review (see Luft4 ).Hypertensinogenic FactorsThere is evidence that obesity, insulin resistance, high alcohol intake, high salt intake, a sedentary lifestyle, stress, dyslipidemia, and low potassium or calcium intake increase BP in susceptible subjects. Here we will briefly discuss obesity and insulin resistance; other hypertensinogenic factors will be discussed in the section "Lifestyle Modification."Obesity and Insulin ResistanceObesity, and obesity, is the main hypertensinogenic It was estimated in the study that is associated with a mm Hg increase in systolic is also the cause of insulin resistance, left and Thus obesity is an important cardiovascular its incidence and prevalence are in most industrialized and in the United States has The between BP and body fat is not to the but is continuous throughout the range of body A direct association between hypertension and in by the in has been in and population studies from early to old A of is considered normal or whereas a of to with increases the risk of high BP by and the risk of insulin resistance by Thus insulin resistance is in many patients with obesity and hypertension. The mechanism by which obesity BP is not but increased is associated with an increase in plasma volume and cardiac both these alterations and BP can be by in both normotensive and hypertensive even when sodium intake is BP in is and fasting insulin is the of this In these BP by 10 mm Hg changing from 2 on a to a When some of these subjects by BP by 10 mm Hg and salt was no longer present. The that sodium fasting plasma plasma aldosterone, and plasma the that BP is to dietary sodium and that this may be due to the combined of and increased activity of the sympathetic nervous It is not clear whether body fat by is a factor because in for 1 3 BP, and this decrease was mainly in those who high fasting insulin and insulin levels in to In this study was not a factor because the subjects on a and actually gained an average of the which that plasma insulin by a different mechanism than of body These studies can be as that high plasma insulin causes salt and that decreasing insulin resistance by or BP. Furthermore, hypertensive subjects are more to exhibit insulin resistance than normotensive the other insulin by has a In subjects with hypertension there is resistance to the of insulin on However, in addition to this metabolic insulin increases both sympathetic nerve activity and sodium and water retention, and it could be that the hypertension is due to the of resistance to these secondary of factor and a that have also been in the of hypertension. although the mechanisms by which obesity and insulin resistance increase BP remain it is clear that these increases in BP are on the inherited of of the evaluation are to determine the and of target organ and for specific causes of hypertension hypertensinogenic factors and other CVD risk factors; and the patient to facilitate the of therapy and define and of BP by the is the most important part of the evaluation and of the patient and be in a 2) with the use of and A is a or a to an arm Two or 3 measurements be at and at least 2 be allowed between The diastolic is at the level when of BP by patients or family and/or BP the diagnosis and the of hypertension. BP values the are lower and better with target organ than BP measurements by of BP has several including hypertension from hypertension that only in the the to antihypertensive to treatment by the patient a in his or her and by the need for BP or of BP is for many patients with high BP, those who to be to antihypertensive A of or BP measurements is that and BP be and that and in to BP be and be and a in all patients The assessment the described in Table It help to known, causes of high the or of target organ and and other CVD or comorbid conditions that might or Tests and only blood blood fasting total and high-density or and a indicated in patients for the diagnosis of secondary hypertension and/or comorbid conditions urinary protein, of fasting and plasma renin is Part of a Part of this will be published in the 1, of 1. of hypertensinogenic factors such as obesity and alcohol intake on systolic and diastolic BP the stage of inherited BP to without the of the hypertensinogenic with normal or high normal inherited BP hypertensive stage 1 when BP is increased by a hypertensinogenic In patients with inherited hypertension in 1 to hypertension more severe when hypertensinogenic factors are among genetic and environmental factors in the development of hypertension. side of environmental factors and multiple genes responsible for high BP and intermediary The result of these intermediary phenotypes is blood pressure with a normal distribution skewed to the right. the theoretical BP of the population that is not affected by hypertensinogenic factors; area systolic BP in the hypertensive range. and dotted populations in which 1 or 2 hypertensinogenic factors high alcohol intake) have been that in these 2 populations the distribution are to the right and the number of hypertensive individuals is increased when hypertensinogenic factors are Table 1. and of Blood Pressure mm mm 1 2 3 systolic a patient's systolic and

Circulation · review · 1085 citationsread the source →

Delaney MC. (2018)MEDLINE-indexed journal, not yet read by usPloS one · cohort or longitudinal

Caring for the caregivers: Evaluation of the effect of an eight-week pilot mindful self-compassion (MSC) training program on nurses' compassion fatigue and resilience.

Background: Nurses vicariously exposed to the suffering of those in their care are at risk of compassion fatigue. Emerging research suggests that self-compassion interventions may provide protective factors and enhance resilience. This pilot study examined the effect of an eight-week Mindful Self-Compassion (MSC) training intervention on nurses' compassion fatigue and resilience and participants' lived experience of the effect of the training. Methods: This observational mixed research pilot study adopted an evaluation design framework. It comprised of a single group and evaluated the effects of a pilot MSC intervention by analyzing the pre- and post-change scores in self-compassion, mindfulness, secondary trauma, burnout, compassion satisfaction, and resilience. The sample of the nurses' (N = 13) written responses to the question, "How did you experience the effect of this pilot MSC training?" were also analyzed. Results: The Pre- to Post- scores of secondary trauma and burnout declined significantly and were negatively associated with self-compassion (r = -.62, p = .02) (r = -.55, p = .05) and mindfulness (r = -.54, p = .05). (r = -.60, p = .03), respectively. Resilience and compassion satisfaction scores increased. All variables demonstrated a large effect size: Mean (M) Cohen's d = 1.23. The qualitative emergent themes corroborated the quantitative findings and expanded the understanding about how MSC on the job practices enhanced nurses' coping. Conclusion: This is the first study to examine the effect of a pilot (MSC) training program on nurses' compassion fatigue and resilience in this new area of research. It provides some preliminary empirical evidence in support of the theorized benefits of self-compassion training for nurses. However, further research, such as a Randomized Control Trial (RCT) with a larger sample size and a longitudinal study, is required to see if the benefits of self-compassion training are sustainable.

PloS one · cohort or longitudinal · 117 citationsread the source →

The unique social sense of puerperium: Increased empathy and Schadenfreude in parents of newborns.

Pregnancy and puerperium are typified by marked biobehavioral changes. These changes, which are traceable in both mothers and fathers, play an important role in parenthood and may modulate social cognition abilities. However, the latter effects remain notably unexplored in parents of newborns (PNs). To bridge this gap, we assessed empathy and social emotions (envy and Schadenfreude) in 55 PNs and 60 controls (childless healthy participants without a romantic relationship or sexual intercourse in the previous 48 hours). We used facial electromyography to detect physiological signatures of social emotion processing. Results revealed higher levels of affective empathy and Schadenfreude in PNs, the latter pattern being accompanied by increased activity of the corrugator suppercilii region. These effects were not explained by potential confounding variables (educational level, executive functioning, depression, stress levels, hours of sleep). Our novel findings suggest that PNs might show social cognition changes crucial for parental bonding and newborn care.

Scientific reports · 16 citationsread the source →

Effect of Multimodal Prehabilitation on Reducing Postoperative Complications and Enhancing Functional Capacity Following Colorectal Cancer Surgery: The PREHAB Randomized Clinical Trial.

Importance: Colorectal surgery is associated with substantial morbidity rates and a lowered functional capacity. Optimization of the patient's condition in the weeks prior to surgery may attenuate these unfavorable sequelae. Objective: To determine whether multimodal prehabilitation before colorectal cancer surgery can reduce postoperative complications and enhance functional recovery. Design, setting, and participants: The PREHAB randomized clinical trial was an international, multicenter trial conducted in teaching hospitals with implemented enhanced recovery after surgery programs. Adult patients with nonmetastasized colorectal cancer were assessed for eligibility and randomized to either prehabilitation or standard care. Both arms received standard perioperative care. Patients were enrolled from June 2017 to December 2020, and follow-up was completed in December 2021. However, this trial was prematurely stopped due to the COVID-19 pandemic. Interventions: The 4-week in-hospital supervised multimodal prehabilitation program consisted of a high-intensity exercise program 3 times per week, a nutritional intervention, psychological support, and a smoking cessation program when needed. Main outcomes and measures: Comprehensive Complication Index (CCI) score, number of patients with CCI score more than 20, and improved walking capacity expressed as the 6-minute walking distance 4 weeks postoperatively. Results: In the intention-to-treat population of 251 participants (median [IQR] age, 69 [60-76] years; 138 [55%] male), 206 (82%) had tumors located in the colon and 234 (93%) underwent laparoscopic- or robotic-assisted surgery. The number of severe complications (CCI score >20) was significantly lower favoring prehabilitation compared with standard care (21 of 123 [17.1%] vs 38 of 128 [29.7%]; odds ratio, 0.47 [95% CI, 0.26-0.87]; P = .02). Participants in prehabilitation encountered fewer medical complications (eg, respiratory) compared with participants receiving standard care (19 of 123 [15.4%] vs 35 of 128 [27.3%]; odds ratio, 0.48 [95% CI, 0.26-0.89]; P = .02). Four weeks after surgery, 6-minute walking distance did not differ significantly between groups when compared with baseline (mean difference prehabilitation vs standard care 15.6 m [95% CI, -1.4 to 32.6]; P = .07). Secondary parameters of functional capacity in the postoperative period generally favored prehabilitation compared with standard care. Conclusions and relevance: This PREHAB trial demonstrates the benefit of a multimodal prehabilitation program before colorectal cancer surgery as reflected by fewer severe and medical complications postoperatively and an optimized postoperative recovery compared with standard care. Trial registration: trialregister.nl Identifier: NTR5947.

JAMA surgery · 362 citationsread the source →

Perkins AM, Meiser-Stedman R, Spaul SW, Bowers G, Perkins AG, Pass L. (2023)MEDLINE-indexed journal, not yet read by usThe British journal of clinical psychology · meta-analysis

The effectiveness of third wave cognitive behavioural therapies for children and adolescents: A systematic review and meta-analysis.

Objectives: Third wave cognitive behavioural therapies are increasingly used with children and adolescents. This meta-analysis aimed to determine the effectiveness of four third-wave interventions (acceptance and commitment therapy, compassion focused therapy, mindfulness-based cognitive therapy, and metacognitive therapy) for youth. Methods: Four electronic databases were used to identify randomized controlled trials, which tested effects related to health, well-being and functioning. Sensitivity analyses considering study quality were conducted and moderators were explored. Results: The results based on 50 RCTs meeting inclusion criteria indicated emotional symptoms/internalizing problems (g = -.68, 95% CI -.98 to -.37, k = 43, N = 3265), behavioural difficulties/externalizing problems (g = -.62, 95% CI -1.01 to -.22, k = 23, N = 1659), interference from difficulties (g = -.46, 95% CI -.87 to -.05, k = 21, N = 1786), third wave processes (g = .39, 95% CI .17 to .62, k = 22, N = 1900), wellbeing/flourishing (g = .76, 95% CI .35 to 1.17, k = 21, N = 1303) and physical health/pain (g = .72, 95% CI .01 to 1.44, k = 9, N = 1171) yielded significant effects. Effect for quality of life (g = .62, 95% CI -.08 to 1.31, k = 12, N = 1271) was non-significant. When analysing only those studies rated moderate-high quality, third wave interventions yielded significant superiority effects compared to controls for emotional symptoms/internalizing problems (g = -.55, 95% CI -.82 to -.27, k = 28, N = 2110), interference from difficulties (g = -.48, 95% CI -.90 to -.05, k = 21, N = 1605), third wave processes (g = .27, 95% CI .11 to .43, k = 18, N = 1692), well-being/flourishing (g = .50, 95% CI .18 to .81, k = 16, N = 1063), and quality of life (g = .32, 95% CI .04 to .60, k = 10, N = 1212). Behavioural difficulties/externalizing problems (g = -.38, 95% CI -.86 to .10, k = 15, N = 1351) and physical health/pain (g = .52, 95% CI -.14 to 1.17, k = 8, N = 1139) ceased to be significant. Widespread heterogeneity raised concerns about generalizability and follow-up data was relatively sparse. Conclusions: This meta-analysis finds promising results for use of third wave CBT with youth, though the review has limitations.

The British journal of clinical psychology · meta-analysis · 19 citationsread the source →

Middleton P, Shepherd E, Flenady V, McBain RD, Crowther CA. (2017)MEDLINE-indexed journal, not yet read by usThe Cochrane database of systematic reviews · meta-analysis

Planned early birth versus expectant management (waiting) for prelabour rupture of membranes at term (37 weeks or more).

Background: Prelabour rupture of membranes (PROM) at term is managed expectantly or by planned early birth. It is not clear if waiting for birth to occur spontaneously is better than intervening, e.g. by inducing labour. Objectives: The objective of this review is to assess the effects of planned early birth (immediate intervention or intervention within 24 hours) when compared with expectant management (no planned intervention within 24 hours) for women with term PROM on maternal, fetal and neonatal outcomes. Search methods: We searched Cochrane Pregnancy and Childbirth's Trials Register (9 September 2016) and reference lists of retrieved studies. Selection criteria: Randomised or quasi-randomised controlled trials of planned early birth compared with expectant management (either in hospital or at home) in women with PROM at 37 weeks' gestation or later. Data collection and analysis: Two review authors independently assessed trials for inclusion, extracted the data, and assessed risk of bias of the included studies. Data were checked for accuracy. Main results: Twenty-three trials involving 8615 women and their babies were included in the update of this review. Ten trials assessed intravenous oxytocin; 12 trials assessed prostaglandins (six trials in the form of vaginal prostaglandin E2 and six as oral, sublingual or vaginal misoprostol); and one trial each assessed Caulophyllum and acupuncture. Overall, three trials were judged to be at low risk of bias, while the other 20 were at unclear or high risk of bias. Primary outcomes: women who had planned early birth were at a reduced risk of maternal infectious morbidity (chorioamnionitis and/or endometritis) than women who had expectant management following term prelabour rupture of membranes (average risk ratio (RR) 0.49; 95% confidence interval (CI) 0.33 to 0.72; eight trials, 6864 women; Tau² = 0.19; I² = 72%; low-quality evidence), and their neonates were less likely to have definite or probable early-onset neonatal sepsis (RR 0.73; 95% CI 0.58 to 0.92; 16 trials, 7314 infants;low-quality evidence). No clear differences between the planned early birth and expectant management groups were seen for the risk of caesarean section (average RR 0.84; 95% CI 0.69 to 1.04; 23 trials, 8576 women; Tau² = 0.10; I² = 55%; low-quality evidence); serious maternal morbidity or mortality (no events; three trials; 425 women; very low-quality evidence); definite early-onset neonatal sepsis (RR 0.57; 95% CI 0.24 to 1.33; six trials, 1303 infants; very low-quality evidence); or perinatal mortality (RR 0.47; 95% CI 0.13 to 1.66; eight trials, 6392 infants; moderate-quality evidence). Secondary outcomes: women who had a planned early birth were at a reduced risk of chorioamnionitis (average RR 0.55; 95% CI 0.37 to 0.82; eight trials, 6874 women; Tau² = 0.19; I² = 73%), and postpartum septicaemia (RR 0.26; 95% CI 0.07 to 0.96; three trials, 263 women), and their neonates were less likely to receive antibiotics (average RR 0.61; 95% CI 0.44 to 0.84; 10 trials, 6427 infants; Tau² = 0.06; I² = 32%). Women in the planned early birth group were more likely to have their labour induced (average RR 3.41; 95% CI 2.87 to 4.06; 12 trials, 6945 women; Tau² = 0.05; I² = 71%), had a shorter time from rupture of membranes to birth (mean difference (MD) -10.10 hours; 95% CI -12.15 to -8.06; nine trials, 1484 women; Tau² = 5.81; I² = 60%), and their neonates had lower birthweights (MD -79.25 g; 95% CI -124.96 to -33.55; five trials, 1043 infants). Women who had a planned early birth had a shorter length of hospitalisation (MD -0.79 days; 95% CI -1.20 to -0.38; two trials, 748 women; Tau² = 0.05; I² = 59%), and their neonates were less likely to be admitted to the neonatal special or intensive care unit (RR 0.75; 95% CI 0.66 to 0.85; eight trials, 6179 infants), and had a shorter duration of hospital (-11.00 hours; 95% CI -21.96 to -0.04; one trial, 182 infants) or special or intensive care unit stay (RR 0.72; 95% CI 0.61 to 0.85; four trials, 5691 infants). Women in the planned early birth group had more positive experiences compared with women in the expectant management group. No clear differences between groups were observed for endometritis; postpartum pyrexia; postpartum antibiotic usage; caesarean for fetal distress; operative vaginal birth; uterine rupture; epidural analgesia; postpartum haemorrhage; adverse effects; cord prolapse; stillbirth; neonatal mortality; pneumonia; Apgar score less than seven at five minutes; use of mechanical ventilation; or abnormality on cerebral ultrasound (no events).None of the trials reported on breastfeeding; postnatal depression; gestational age at birth; meningitis; respiratory distress syndrome; necrotising enterocolitis; neonatal encephalopathy; or disability at childhood follow-up. In subgroup analyses, there were no clear patterns of differential effects for method of induction, parity, use of maternal antibiotic prophylaxis, or digital vaginal examination. Results of the sensitivity analyses based on trial quality were consistent with those of the main analysis, except for definite or probable early-onset neonatal sepsis where no clear difference was observed. Authors' conclusions: There is low quality evidence to suggest that planned early birth (with induction methods such as oxytocin or prostaglandins) reduces the risk of maternal infectious morbidity compared with expectant management for PROM at 37 weeks' gestation or later, without an apparent increased risk of caesarean section. Evidence was mainly downgraded due to the majority of studies contributing data having some serious design limitations, and for most outcomes estimates were imprecise. Although the 23 included trials in this review involved a large number of women and babies, the quality of the trials and evidence was not high overall, and there was limited reporting for a number of important outcomes. Thus further evidence assessing the benefits or harms of planned early birth compared with expectant management, considering maternal, fetal, neonatal and longer-term childhood outcomes, and the use of health services, would be valuable. Any future trials should be adequately designed and powered to evaluate the effects on short- and long-term outcomes. Standardisation of outcomes and their definitions, including for the assessment of maternal and neonatal infection, would be beneficial.

The Cochrane database of systematic reviews · meta-analysis · 75 citationsread the source →

Kaner EF, Beyer FR, Muirhead C, Campbell F, Pienaar ED, Bertholet N, Daeppen JB, Saunders JB, Burnand B. (2018)MEDLINE-indexed journal, not yet read by usThe Cochrane database of systematic reviews · meta-analysis

Effectiveness of brief alcohol interventions in primary care populations.

Background: Excessive drinking is a significant cause of mortality, morbidity and social problems in many countries. Brief interventions aim to reduce alcohol consumption and related harm in hazardous and harmful drinkers who are not actively seeking help for alcohol problems. Interventions usually take the form of a conversation with a primary care provider and may include feedback on the person's alcohol use, information about potential harms and benefits of reducing intake, and advice on how to reduce consumption. Discussion informs the development of a personal plan to help reduce consumption. Brief interventions can also include behaviour change or motivationally-focused counselling. This is an update of a Cochrane Review published in 2007. Objectives: To assess the effectiveness of screening and brief alcohol intervention to reduce excessive alcohol consumption in hazardous or harmful drinkers in general practice or emergency care settings. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and 12 other bibliographic databases to September 2017. We searched Alcohol and Alcohol Problems Science Database (to December 2003, after which the database was discontinued), trials registries, and websites. We carried out handsearching and checked reference lists of included studies and relevant reviews. Selection criteria: We included randomised controlled trials (RCTs) of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. The comparison group was no or minimal intervention, where a measure of alcohol consumption was reported. 'Brief intervention' was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 minutes. Any more was considered an extended intervention. Digital interventions were not included in this review. Data collection and analysis: We used standard methodological procedures expected by Cochrane. We carried out subgroup analyses where possible to investigate the impact of factors such as gender, age, setting (general practice versus emergency care), treatment exposure and baseline consumption. Main results: We included 69 studies that randomised a total of 33,642 participants. Of these, 42 studies were added for this update (24,057 participants). Most interventions were delivered in general practice (38 studies, 55%) or emergency care (27 studies, 39%) settings. Most studies (61 studies, 88%) compared brief intervention to minimal or no intervention. Extended interventions were compared with brief (4 studies, 6%), minimal or no intervention (7 studies, 10%). Few studies targeted particular age groups: adolescents or young adults (6 studies, 9%) and older adults (4 studies, 6%). Mean baseline alcohol consumption was 244 g/week (30.5 standard UK units) among the studies that reported these data. Main sources of bias were attrition and lack of provider or participant blinding. The primary meta-analysis included 34 studies (15,197 participants) and provided moderate-quality evidence that participants who received brief intervention consumed less alcohol than minimal or no intervention participants after one year (mean difference (MD) -20 g/week, 95% confidence interval (CI) -28 to -12). There was substantial heterogeneity among studies (I² = 73%). A subgroup analysis by gender demonstrated that both men and women reduced alcohol consumption after receiving a brief intervention. We found moderate-quality evidence that brief alcohol interventions have little impact on frequency of binges per week (MD -0.08, 95% CI -0.14 to -0.02; 15 studies, 6946 participants); drinking days per week (MD -0.13, 95% CI -0.23 to -0.04; 11 studies, 5469 participants); or drinking intensity (-0.2 g/drinking day, 95% CI -3.1 to 2.7; 10 studies, 3128 participants).We found moderate-quality evidence of little difference in quantity of alcohol consumed when extended and no or minimal interventions were compared (-14 g/week, 95% CI -37 to 9; 6 studies, 1296 participants). There was little difference in binges per week (-0.08, 95% CI -0.28 to 0.12; 2 studies, 456 participants; moderate-quality evidence) or difference in days drinking per week (-0.45, 95% CI -0.81 to -0.09; 2 studies, 319 participants; moderate-quality evidence). Extended versus no or minimal intervention provided little impact on drinking intensity (9 g/drinking day, 95% CI -26 to 9; 1 study, 158 participants; low-quality evidence).Extended intervention had no greater impact than brief intervention on alcohol consumption, although findings were imprecise (MD 2 g/week, 95% CI -42 to 45; 3 studies, 552 participants; low-quality evidence). Numbers of binges were not reported for this comparison, but one trial suggested a possible drop in days drinking per week (-0.5, 95% CI -1.2 to 0.2; 147 participants; low-quality evidence). Results from this trial also suggested very little impact on drinking intensity (-1.7 g/drinking day, 95% CI -18.9 to 15.5; 147 participants; very low-quality evidence).Only five studies reported adverse effects (very low-quality evidence). No participants experienced any adverse effects in two studies; one study reported that the intervention increased binge drinking for women and two studies reported adverse events related to driving outcomes but concluded they were equivalent in both study arms. Sources of funding were reported by 67 studies (87%). With two exceptions, studies were funded by government institutes, research bodies or charitable foundations. One study was partly funded by a pharmaceutical company and a brewers association, another by a company developing diagnostic testing equipment. Authors' conclusions: We found moderate-quality evidence that brief interventions can reduce alcohol consumption in hazardous and harmful drinkers compared to minimal or no intervention. Longer counselling duration probably has little additional effect. Future studies should focus on identifying the components of interventions which are most closely associated with effectiveness.

The Cochrane database of systematic reviews · meta-analysis · 409 citationsread the source →

Rogers JP, Chesney E, Oliver D, Pollak TA, McGuire P, Fusar-Poli P, Zandi MS, Lewis G, David AS. (2020)MEDLINE-indexed journal, not yet read by usThe lancet. Psychiatry · meta-analysis

Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic.

Background: Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality. Findings: 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5-36·0] of 129 patients), depressed mood (42 [32·6%; 24·7-40·9] of 129), anxiety (46 [35·7%; 27·6-44·2] of 129), impaired memory (44 [34·1%; 26·2-42·5] of 129), and insomnia (54 [41·9%; 22·5-50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5-14·1] of 332 patients), insomnia (34 [12·1%; 8·6-16·3] of 280), anxiety (21 [12·3%; 7·7-17·7] of 171), irritability (28 [12·8%; 8·7-17·6] of 218), memory impairment (44 [18·9%; 14·1-24·2] of 233), fatigue (61 [19·3%; 15·1-23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9-37·3] of 181) and sleep disorder (14 [100·0%; 88·0-100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7-42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1-18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1-19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1-84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation: If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.

The lancet. Psychiatry · meta-analysis · 1531 citationsread the source →

Flodgren G, Rachas A, Farmer AJ, Inzitari M, Shepperd S. (2015)MEDLINE-indexed journal, not yet read by usThe Cochrane database of systematic reviews · meta-analysis

Interactive telemedicine: effects on professional practice and health care outcomes.

Background: Telemedicine (TM) is the use of telecommunication systems to deliver health care at a distance. It has the potential to improve patient health outcomes, access to health care and reduce healthcare costs. As TM applications continue to evolve it is important to understand the impact TM might have on patients, healthcare professionals and the organisation of care. Objectives: To assess the effectiveness, acceptability and costs of interactive TM as an alternative to, or in addition to, usual care (i.e. face-to-face care, or telephone consultation). Search methods: We searched the Effective Practice and Organisation of Care (EPOC) Group's specialised register, CENTRAL, MEDLINE, EMBASE, five other databases and two trials registers to June 2013, together with reference checking, citation searching, handsearching and contact with study authors to identify additional studies. Selection criteria: We considered randomised controlled trials of interactive TM that involved direct patient-provider interaction and was delivered in addition to, or substituting for, usual care compared with usual care alone, to participants with any clinical condition. We excluded telephone only interventions and wholly automatic self-management TM interventions. Data collection and analysis: For each condition, we pooled outcome data that were sufficiently homogenous using fixed effect meta-analysis. We reported risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes, and mean differences (MD) for continuous outcomes. Main results: We included 93 eligible trials (N = 22,047 participants), which evaluated the effectiveness of interactive TM delivered in addition to (32% of studies), as an alternative to (57% of studies), or partly substituted for usual care (11%) as compared to usual care alone. The included studies recruited patients with the following clinical conditions: cardiovascular disease (36), diabetes (21), respiratory conditions (9), mental health or substance abuse conditions (7), conditions requiring a specialist consultation (6), co morbidities (3), urogenital conditions (3), neurological injuries and conditions (2), gastrointestinal conditions (2), neonatal conditions requiring specialist care (2), solid organ transplantation (1), and cancer (1).Telemedicine provided remote monitoring (55 studies), or real-time video-conferencing (38 studies), which was used either alone or in combination. The main TM function varied depending on clinical condition, but fell typically into one of the following six categories, with some overlap: i) monitoring of a chronic condition to detect early signs of deterioration and prompt treatment and advice, (41); ii) provision of treatment or rehabilitation (12), for example the delivery of cognitive behavioural therapy, or incontinence training; iii) education and advice for self-management (23), for example nurses delivering education to patients with diabetes or providing support to parents of very low birth weight infants or to patients with home parenteral nutrition; iv) specialist consultations for diagnosis and treatment decisions (8), v) real-time assessment of clinical status, for example post-operative assessment after minor operation or follow-up after solid organ transplantation (8) vi), screening, for angina (1).The type of data transmitted by the patient, the frequency of data transfer, (e.g. telephone, e-mail, SMS) and frequency of interactions between patient and healthcare provider varied across studies, as did the type of healthcare provider/s and healthcare system involved in delivering the intervention. We found no difference between groups for all-cause mortality for patients with heart failure (16 studies; N = 5239; RR:0.89, 95% CI 0.76 to 1.03, P = 0.12; I(2) = 44%) (moderate to high certainty of evidence) at a median of six months follow-up. Admissions to hospital (11 studies; N = 4529) ranged from a decrease of 64% to an increase of 60% at median eight months follow-up (moderate certainty of evidence). We found some evidence of improved quality of life (five studies; N = 482; MD:-4.39, 95% CI -7.94 to -0.83; P < 0.02; I(2) = 0%) (moderate certainty of evidence) for those allocated to TM as compared with usual care at a median three months follow-up. In studies recruiting participants with diabetes (16 studies; N = 2768) we found lower glycated haemoglobin (HbA1c %) levels in those allocated to TM than in controls (MD -0.31, 95% CI -0.37 to -0.24; P < 0.00001; I(2)= 42%, P = 0.04) (high certainty of evidence) at a median of nine months follow-up. We found some evidence for a decrease in LDL (four studies, N = 1692; MD -12.45, 95% CI -14.23 to -10.68; P < 0.00001; I(2 =) 0%) (moderate certainty of evidence), and blood pressure (four studies, N = 1770: MD: SBP:-4.33, 95% CI -5.30 to -3.35, P < 0.00001; I(2) = 17%; DBP: -2.75 95% CI -3.28 to -2.22, P < 0.00001; I(2) = 45% (moderate certainty evidence), in TM as compared with usual care. Seven studies that recruited participants with different mental health and substance abuse problems, reported no differences in the effect of therapy delivered over video-conferencing, as compared to face-to-face delivery. Findings from the other studies were inconsistent; there was some evidence that monitoring via TM improved blood pressure control in participants with hypertension, and a few studies reported improved symptom scores for those with a respiratory condition. Studies recruiting participants requiring mental health services and those requiring specialist consultation for a dermatological condition reported no differences between groups. Authors' conclusions: The findings in our review indicate that the use of TM in the management of heart failure appears to lead to similar health outcomes as face-to-face or telephone delivery of care; there is evidence that TM can improve the control of blood glucose in those with diabetes. The cost to a health service, and acceptability by patients and healthcare professionals, is not clear due to limited data reported for these outcomes. The effectiveness of TM may depend on a number of different factors, including those related to the study population e.g. the severity of the condition and the disease trajectory of the participants, the function of the intervention e.g., if it is used for monitoring a chronic condition, or to provide access to diagnostic services, as well as the healthcare provider and healthcare system involved in delivering the intervention.

The Cochrane database of systematic reviews · meta-analysis · 456 citationsread the source →

Vitamin A supplementation for extremely low birth weight infants: outcome at 18 to 22 months.

Background: A National Institute of Child Health and Human Development Neonatal Research Network randomized trial showed that vitamin A supplementation reduced bronchopulmonary dysplasia (O2 at 36 weeks' postmenstrual age) or death in extremely low birth weight (ELBW) neonates (relative risk [RR]: 0.89). As with postnatal steroids or other interventions, it is important to ensure that there are no longer-term adverse effects that outweigh neonatal benefits. Primary objective: To determine if vitamin A supplementation in ELBW infants during the first month after birth affects survival without neurodevelopmental impairment at a corrected age of 18 to 22 months. Design/methods: Infants enrolled in the National Institute of Child Health and Human Development vitamin A trial were evaluated at 18 to 22 months by carefully standardized assessments: Bayley Mental Index (MDI) and Psychomotor Index (PDI), visual and hearing screens, and physical examination for cerebral palsy (CP). The medical history was also obtained. Neurodevelopmental impairment (NDI) was predefined as > or =1 of MDI <70, PDI <70, CP, blind in both eyes, or hearing aids in both ears. Results: Of 807 enrolled infants, 133 died before and 16 died after discharge. Five hundred seventy-nine (88%) of the 658 remaining infants were followed up. The primary outcome of NDI or death could be determined for 687 of 807 randomized infants (85%). Baseline characteristics and predischarge and postdischarge mortality were comparable in both study groups. NDI or death by 18 to 22 months occurred in 190 of 345 (55%) infants in the vitamin A group and in 204 of 342 (60%) of the control group (RR: 0.94; 95% confidence interval: 0.80-1.07). RRs for low MDI, low PDI, and CP were also <1.0. We found no evidence that neonatal vitamin A supplementation reduces hospitalizations or pulmonary problems after discharge. Conclusion: Vitamin A supplementation for ELBW infants reduces bronchopulmonary dysplasia without increasing mortality or neurodevelopmental impairment at 18 to 22 months. However, this study was not powered to evaluate small magnitudes of change in long-term outcomes.

Pediatrics · randomised controlled trial · 80 citationsread the source →

Bloom JR, Stewart SL, Oakley-Girvan I, Banks PJ, Shema S. (2012)MEDLINE-indexed journal, not yet read by usPsycho-oncology

Quality of life of younger breast cancer survivors: persistence of problems and sense of well-being.

Objective: Ten years after diagnosis, women diagnosed with breast cancer at age 50 or younger were assessed to determine whether quality of life (QOL) problems found at five years persisted. We predicted that QOL in the physical and social domains would be poorer, but improvements would be found in the psychological domain. Methods: We re-interviewed 312 women, who had been interviewed at their five year anniversary and remained cancer free, on their QOL in three domains (physical, social, and psychological). Comparisons between their 5- and 10-year reports were performed using paired t-tests for numeric variables and McNemar's test for categorical variables. Multiple regression analysis was used to model change from 5 to 10 years in each QOL domain, given the level of QOL at 5 years. Results: The women's mean age was 55, 60% were college graduates, 79% had a partner, and 27% were non-Euro-American. Ten years after diagnosis they reported poorer general health (p<0.0001) and physical well-being (p = 0.001), less sexual activity (p = 0.009), and more chronic conditions (p<0.0001) than at 5 years. Relationships were found between: (1) the number of chronic conditions at 5 years and decreased physical, social, and psychological well-being at 10 years; and (2) a smaller social network at 5 years and poorer social functioning at 10 years. Conclusions: Certain aspects of both physical and social QOL worsened over time. The remaining question is whether these changes can be attributed to the late effects of treatment or to normal effects of aging.

Psycho-oncology · 57 citationsread the source →

Moreno-Lopez L, Contreras-Rodriguez O, Soriano-Mas C, Stamatakis EA, Verdejo-Garcia A. (2016)MEDLINE-indexed journal, not yet read by usNeuroImage. Clinical

Disrupted functional connectivity in adolescent obesity.

Background/objective: Obesity has been associated with brain alterations characterised by poorer interaction between a hypersensitive reward system and a comparatively weaker prefrontal-cognitive control system. These alterations may occur as early as in adolescence, but this notion remains unclear, as no studies so far have examined global functional connectivity in adolescents with excess weight. Subjects/methods: We investigated functional connectivity in a sample of 60 adolescents with excess weight and 55 normal weight controls. We first identified parts of the brain displaying between-group global connectivity differences and then characterised the extent of the differences in functional network integrity and their association with reward sensitivity. Results: Adolescent obesity was linked to neuroadaptations in functional connectivity within brain hubs linked to interoception (insula), emotional memory (middle temporal gyrus) and cognitive control (dorsolateral prefrontal cortex) (pFWE < 0.05). The connectivity between the insula and the anterior cingulate cortex was reduced in comparison to controls, as was the connectivity between the middle temporal gyrus and the posterior cingulate cortex and cuneus/precuneus (pFWE < 0.05). Conversely, the middle temporal gyrus displayed increased connectivity with the orbitofrontal cortex (pFWE < 0.05). Critically, these networks were correlated with sensitivity to reward (p < 0.05). Conclusions: These findings suggest that adolescent obesity is linked to disrupted functional connectivity in brain networks relevant to maintaining balance between reward, emotional memories and cognitive control. Our findings may contribute to reconceptualization of obesity as a multi-layered brain disorder leading to compromised motivation and control, and provide a biological account to target prevention strategies for adolescent obesity.

NeuroImage. Clinical · 66 citationsread the source →

Jeuland J, Fitchett G, Schulman-Green D, Kapo J. (2017)MEDLINE-indexed journal, not yet read by usJournal of palliative medicine

Chaplains Working in Palliative Care: Who They Are and What They Do.

Background: Palliative care (PC) programs utilize chaplains to address patients' spiritual care needs; however, there is no comprehensive description of chaplaincy in PC programs nationally. Objective: To describe chaplains working in PC across the United States, including their integration on the PC team and visit content. Design: National online survey conducted February-April 2015. Subjects: We invited participation from hospital-based chaplains belonging to four national professional chaplain associations who spent 15% or more of their working hours with PC teams. Measure(s): We developed a 41-item survey to investigate main outcomes of chaplain demographics, practice information, integration into the PC team, and visit content. Results: 531 valid responses were received. We report on respondents who were full-time chaplains (n = 382). Almost half were women (46%), and the majority was Protestant (70%). The average number of PC patients seen per day was 5.2 (SD = 3.5, range 1-30). Half (52%) reported frequently participating in PC rounds. Primary chaplain activities were relationship building (76%), care at the time of death (69%), and helping patients with existential issues or spiritual distress (49%). Over half (55%) reported addressing goals of care 60% of the time or more. Discussion: This survey provides the first description of chaplains working in PC across the United States. We describe chaplains' critical role in attending to relationship building, care for the dying, and goals of care conversations. Our results highlight how the chaplains' level of involvement in PC affects the content of their visits. Our study suggests that when chaplains are more involved in PC teams, they provide more comprehensive support to PC patients and their families.

Journal of palliative medicine · 57 citationsread the source →

Gamification for health promotion: systematic review of behaviour change techniques in smartphone apps.

Objective: Smartphone games that aim to alter health behaviours are common, but there is uncertainty about how to achieve this. We systematically reviewed health apps containing gaming elements analysing their embedded behaviour change techniques. Methods: Two trained researchers independently coded apps for behaviour change techniques using a standard taxonomy. We explored associations with user ratings and price. Data sources: We screened the National Health Service (NHS) Health Apps Library and all top-rated medical, health and wellness and health and fitness apps (defined by Apple and Google Play stores based on revenue and downloads). We included free and paid English language apps using 'gamification' (rewards, prizes, avatars, badges, leaderboards, competitions, levelling-up or health-related challenges). We excluded apps targeting health professionals. Results: 64 of 1680 (4%) health apps included gamification and met inclusion criteria; only 3 of these were in the NHS Library. Behaviour change categories used were: feedback and monitoring (n=60, 94% of apps), reward and threat (n=52, 81%), and goals and planning (n=52, 81%). Individual techniques were: self-monitoring of behaviour (n=55, 86%), non-specific reward (n=49, 82%), social support unspecified (n=48, 75%), non-specific incentive (n=49, 82%) and focus on past success (n=47, 73%). Median number of techniques per app was 14 (range: 5-22). Common combinations were: goal setting, self-monitoring, non-specific reward and non-specific incentive (n=35, 55%); goal setting, self-monitoring and focus on past success (n=33, 52%). There was no correlation between number of techniques and user ratings (p=0.07; rs=0.23) or price (p=0.45; rs=0.10). Conclusions: Few health apps currently employ gamification and there is a wide variation in the use of behaviour change techniques, which may limit potential to improve health outcomes. We found no correlation between user rating (a possible proxy for health benefits) and game content or price. Further research is required to evaluate effective behaviour change techniques and to assess clinical outcomes. Trial registration number: CRD42015029841.

BMJ open · systematic review · 209 citationsread the source →

Jackson S, Brown J, Norris E, Livingstone-Banks J, Hayes E, Lindson N. (2022)MEDLINE-indexed journal, not yet read by usThe Cochrane database of systematic reviews · systematic review

Mindfulness for smoking cessation.

Background: Mindfulness-based smoking cessation interventions may aid smoking cessation by teaching individuals to pay attention to, and work mindfully with, negative affective states, cravings, and other symptoms of nicotine withdrawal. Types of mindfulness-based interventions include mindfulness training, which involves training in meditation; acceptance and commitment therapy (ACT); distress tolerance training; and yoga. Objectives: To assess the efficacy of mindfulness-based interventions for smoking cessation among people who smoke, and whether these interventions have an effect on mental health outcomes. Search methods: We searched the Cochrane Tobacco Addiction Group's specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries to 15 April 2021. We also employed an automated search strategy, developed as part of the Human Behaviour Change Project, using Microsoft Academic. Selection criteria: We included randomised controlled trials (RCTs) and cluster-RCTs that compared a mindfulness-based intervention for smoking cessation with another smoking cessation programme or no treatment, and assessed smoking cessation at six months or longer. We excluded studies that solely recruited pregnant women. Data collection and analysis: We followed standard Cochrane methods. We measured smoking cessation at the longest time point, using the most rigorous definition available, on an intention-to-treat basis. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for smoking cessation for each study, where possible. We grouped eligible studies according to the type of intervention and type of comparator. We carried out meta-analyses where appropriate, using Mantel-Haenszel random-effects models. We summarised mental health outcomes narratively. Main results: We included 21 studies, with 8186 participants. Most recruited adults from the community, and the majority (15 studies) were conducted in the USA. We judged four of the studies to be at low risk of bias, nine at unclear risk, and eight at high risk. Mindfulness-based interventions varied considerably in design and content, as did comparators, therefore, we pooled small groups of relatively comparable studies. We did not detect a clear benefit or harm of mindfulness training interventions on quit rates compared with intensity-matched smoking cessation treatment (RR 0.99, 95% CI 0.67 to 1.46; I2 = 0%; 3 studies, 542 participants; low-certainty evidence), less intensive smoking cessation treatment (RR 1.19, 95% CI 0.65 to 2.19; I2 = 60%; 5 studies, 813 participants; very low-certainty evidence), or no treatment (RR 0.81, 95% CI 0.43 to 1.53; 1 study, 325 participants; low-certainty evidence). In each comparison, the 95% CI encompassed benefit (i.e. higher quit rates), harm (i.e. lower quit rates) and no difference. In one study of mindfulness-based relapse prevention, we did not detect a clear benefit or harm of the intervention over no treatment (RR 1.43, 95% CI 0.56 to 3.67; 86 participants; very low-certainty evidence). We did not detect a clear benefit or harm of ACT on quit rates compared with less intensive behavioural treatments, including nicotine replacement therapy alone (RR 1.27, 95% CI 0.53 to 3.02; 1 study, 102 participants; low-certainty evidence), brief advice (RR 1.27, 95% CI 0.59 to 2.75; 1 study, 144 participants; very low-certainty evidence), or less intensive ACT (RR 1.00, 95% CI 0.50 to 2.01; 1 study, 100 participants; low-certainty evidence). There was a high level of heterogeneity (I2 = 82%) across studies comparing ACT with intensity-matched smoking cessation treatments, meaning it was not appropriate to report a pooled result. We did not detect a clear benefit or harm of distress tolerance training on quit rates compared with intensity-matched smoking cessation treatment (RR 0.87, 95% CI 0.26 to 2.98; 1 study, 69 participants; low-certainty evidence) or less intensive smoking cessation treatment (RR 1.63, 95% CI 0.33 to 8.08; 1 study, 49 participants; low-certainty evidence). We did not detect a clear benefit or harm of yoga on quit rates compared with intensity-matched smoking cessation treatment (RR 1.44, 95% CI 0.40 to 5.16; 1 study, 55 participants; very low-certainty evidence). Excluding studies at high risk of bias did not substantially alter the results, nor did using complete case data as opposed to using data from all participants randomised. Nine studies reported on changes in mental health and well-being, including depression, anxiety, perceived stress, and negative and positive affect. Variation in measures and methodological differences between studies meant we could not meta-analyse these data. One study found a greater reduction in perceived stress in participants who received a face-to-face mindfulness training programme versus an intensity-matched programme. However, the remaining eight studies found no clinically meaningful differences in mental health and well-being between participants who received mindfulness-based treatments and participants who received another treatment or no treatment (very low-certainty evidence). Authors' conclusions: We did not detect a clear benefit of mindfulness-based smoking cessation interventions for increasing smoking quit rates or changing mental health and well-being. This was the case when compared with intensity-matched smoking cessation treatment, less intensive smoking cessation treatment, or no treatment. However, the evidence was of low and very low certainty due to risk of bias, inconsistency, and imprecision, meaning future evidence may very likely change our interpretation of the results. Further RCTs of mindfulness-based interventions for smoking cessation compared with active comparators are needed. There is also a need for more consistent reporting of mental health and well-being outcomes in studies of mindfulness-based interventions for smoking cessation.

The Cochrane database of systematic reviews · systematic review · 33 citationsread the source →

Vanderlinden J, Boen F, van Uffelen JGZ. (2020)MEDLINE-indexed journal, not yet read by usThe international journal of behavioral nutrition and physical activity · systematic review

Effects of physical activity programs on sleep outcomes in older adults: a systematic review.

Background: One in two older adults report sleep problems, which not only cause fatigue, but also negatively affect general functioning, activities of daily living, and physical and mental health. Although it is known that physical activity is positively associated with sleep in older adults, the effects of physical activity programs on sleep in older adults has not been reviewed. The aim of this systematic review was to systematically review the effects of physical activity programs on sleep in generally healthy older adults aged 60+ years. Methods: Searches were performed in PubMed, Embase, Web of Science, SPORTDiscus, PEDro and CINAHL. The methodological quality of the included studies was rated using the 'Quality Assessment Tool for Quantitative Studies'. Only studies of moderate and strong quality were included. This review was registered in PROSPERO (CRD42018094007). Results: Fourteen studies met the inclusion criteria (six randomised controlled trials and eight pretest-posttest studies). Of these studies, five were moderate and nine were strong quality studies. Mean age of study samples ranged from 64 to 76 years. Exercise programs included various activities aimed at improving mobility, endurance and strength. Intervention duration ranged from 2 weeks to 12 months. Eleven studies used subjective measures of sleep, two used objective measures and one used both. Sixteen different sleep outcomes were reported. All but one study, found at least one significant improvement on sleep outcomes. No significantly detrimental effects were reported. Effect sizes, calculated in ten studies, ranged from 0,34-1,55 and were substantial (≥0,8) in four studies. Conclusions: This systematic review suggests that exercise programs positively affect various aspects of sleep in generally healthy older adults. More specifically, moderate intensity exercise programs, with a frequency of three times per week and a duration of 12 weeks up to 6 months, showed the highest number of significant improvements in different sleep outcomes in older adults. Furthermore, programs that offered single exercise types, such as Baduanjin, Tai chi and the silver yoga program, or a combination of exercises showed the highest proportion of significant versus reported effects on sleep outcomes.

The international journal of behavioral nutrition and physical activity · systematic review · 148 citationsread the source →

Chavez DA, Garten RS, Rodriguez-Miguelez P, Kim Y, Gagnon D, Romero SA, Kidd JM, Kirkman DL. (2026)MEDLINE-indexed journal, not yet read by usAmerican journal of physiology. Heart and circulatory physiology · randomised controlled trial

Acute effects of passive heat exposure on vascular function and exercise capacity in patients with chronic kidney disease.

Vascular dysfunction and exercise intolerance contribute to chronic kidney disease (CKD)-related cardiovascular disease. Passive heat exposure provides a physiological stimulus for beneficial vascular adaptations and improvements in exercise capacity but has not yet been investigated in CKD. The purpose of this pilot study was to examine the physiological response to an acute bout of passive heat exposure in patients with CKD. In this randomized, crossover trial, 10 participants with Stage G2-G4 CKD were enrolled (means ± SE; age, 41 ± 4 yr; 6 females; estimated glomerular filtration rate, 55 ± 7 mL/min/1.73 m2). After completing a baseline visit, participants completed two experimental visits: passive heat exposure via far-infrared sauna (HT; 25 min, 60°C) and thermoneutral control (CON; 25 min, 22°C). Macrovascular function, assessed by flow-mediated dilation (FMD), and microvascular function, assessed by the blood flow response to passive limb movement, were measured after a 60-min recovery period following exposure on each experimental visit. Exercise capacity was assessed with the 6-min walk test. Urinary markers of kidney function and injury were collected immediately and over 24 h following visits. FMD (3.84 ± 0.61 vs. 6.68 ± 0.76%, P < 0.01) and leg blood flow response to passive limb movement (area under the curve, 179 ± 29 vs. 243 ± 23 arbitrary units, P = 0.01) were greater following HT compared with CON. There was a clinically meaningful difference in 6-min walk distance between CON (632 ± 29 yards) and HT (670 ± 30 yards, P < 0.01). There were no significant changes in kidney function or biomarkers of acute kidney injury following HT. In this pilot study, a single bout of passive heat exposure acutely improved vascular function and exercise capacity in patients with CKD.NEW & NOTEWORTHY This is the first known study to examine the acute vascular, renal, and exercise response to a single bout of passive heat exposure in chronic kidney disease (CKD). Macrovascular function, microvascular function, and exercise capacity were acutely greater after a single session of passive heating, without any effect on kidney function or markers of kidney injury. These preliminary pilot findings could inform future clinical trials of chronic heat therapy for cardiovascular health in CKD.

American journal of physiology. Heart and circulatory physiology · randomised controlled trialread the source →

Hill AM, McPhail SM, Waldron N, Etherton-Beer C, Ingram K, Flicker L, Bulsara M, Haines TP. (2015)MEDLINE-indexed journal, not yet read by usLancet (London, England) · randomised controlled trial

Fall rates in hospital rehabilitation units after individualised patient and staff education programmes: a pragmatic, stepped-wedge, cluster-randomised controlled trial.

Background: Falls are the most frequent adverse events that are reported in hospitals. We examined the effectiveness of individualised falls-prevention education for patients, supported by training and feedback for staff, delivered as a ward-level programme. Methods: Eight rehabilitation units in general hospitals in Australia participated in this stepped-wedge, cluster-randomised study, undertaken during a 50 week period. Units were randomly assigned to intervention or control groups by use of computer-generated, random allocation sequences. We included patients admitted to the unit during the study with a Mini-Mental State Examination (MMSE) score of more than 23/30 to receive individualised education that was based on principles of changes in health behaviour from a trained health professional, in addition to usual care. We provided information about patients' goals, feedback about the ward environment, and perceived barriers to engagement in falls-prevention strategies to staff who were trained to support the uptake of strategies by patients. The coprimary outcome measures were patient rate of falls per 1000 patient-days and the proportion of patients who were fallers. All analyses were by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials registry, number ACTRN12612000877886). Findings: Between Jan 13, and Dec 27, 2013, 3606 patients were admitted to the eight units (n=1983 control period; n=1623 intervention period). There were fewer falls (n=196, 7·80/1000 patient-days vs n=380, 13·78/1000 patient-days, adjusted rate ratio 0·60 [robust 95% CI 0·42-0·94], p=0·003), injurious falls (n=66, 2·63/1000 patient-days vs 131, 4·75/1000 patient-days, 0·65 [robust 95% CI 0·42-0·88], p=0·006), and fallers (n=136 [8·38%] vs n=248 [12·51%] adjusted odds ratio 0·55 [robust 95% CI 0·38 to 0·81], p=0·003) in the intervention compared with the control group. There was no significant difference in length of stay (intervention median 11 days [IQR 7-19], control 10 days [6-18]). Interpretation: Individualised patient education programmes combined with training and feedback to staff added to usual care reduces the rates of falls and injurious falls in older patients in rehabilitation hospital-units. Funding: State Health Research Advisory Council, Department of Health, Government of Western Australia.

Lancet (London, England) · randomised controlled trial · 143 citationsread the source →

Ghadiri Vasfi M, Moradi-Lakeh M, Esmaeili N, Soleimani N, Hajebi A. (2015)MEDLINE-indexed journal, not yet read by usPsychiatric services (Washington, D.C.) · randomised controlled trial

Efficacy of aftercare services for people with severe mental disorders in Iran: a randomized controlled trial.

Objectives: This study aimed to determine whether aftercare services reduced the number of rehospitalizations and length of hospital stay among patients with severe mental disorders. Methods: A total of 120 patients with schizophrenia and schizoaffective or bipolar disorder between the ages of 15 and 65 were recruited from 2010 to 2012 for a randomized controlled trial. The participants were followed up for 20 months after discharge from a university-affiliated hospital in Tehran, Iran. The selection procedure was random sampling. Sixty patients received aftercare services, which included treatment follow-up, family psychoeducation, and patient social skills training, and 60 patients received treatment as usual. Number of hospitalizations and length of hospital stay were primary outcome measures, and severity of psychopathology and severity of illness were secondary outcome measures. The quantitative primary and secondary outcomes measures were compared by using repeated-measures analysis. Results: Three members of the control group did not complete the study. The cumulative number of hospitalizations during the follow-up period was 55 for the control group and 26 for the intervention group. Length of stay was significantly greater in the control group compared with the intervention group (rate ratio=2.38, 95% confidence interval=2.17-2.62). Psychopathology was less severe in the intervention group compared with the control group (p<.001). Conclusions: Aftercare services are efficacious for reducing both the need for rehospitalization and the severity of psychopathology.

Psychiatric services (Washington, D.C.) · randomised controlled trial · 15 citationsread the source →

Wang L, Zhang J, Guo C, He J, Zhang S, Wang Y, Zhao Y, Li L, Wang J, Hou L, Li S, Wang Y, Hao L, Zhao Y, Wu M, Fang J, Rong P. (2022)MEDLINE-indexed journal, not yet read by usBrain stimulation · randomised controlled trial

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in patients with mild cognitive impairment: A double blinded randomized clinical trial.

Background: There are 9.9 million new cases of dementia in the world every year. Short-term conversion rate from mild cognitive impairment (MCI) to dementia is between 20% and 40%, but long-term in 5-10 years ranges from 60% to 100%. It is particularly important to prevent or prolong the development of MCI into dementia. Both auriculotherapy and vagus nerve stimulation are effective on improving cognitive functions. However, there is no double blinded randomized clinical trial to support the effectiveness of transcutaneous electrical stimulation of auricular acupoints in patients with MCI. Methods: This randomized controlled trial involved patients with MCI, aged from 55 to 75 years old. Patients were randomly allocated to transcutaneous auricular vagus nerve stimulation (taVNS) group or sham taVNS group. In the taVNS group, two auricular acupoints were stimulated, including heart (concha, CO15) and kidney (CO10), which are in the distribution of vagus nerve. While in the sham taVNS group, two other auricular acupoints were stimulated, including elbow (scaphoid fossa, SF3) and shoulder (SF4,5), which are out of the distribution of vagus nerve. The primary outcome was the Montreal cognitive assessment-basic, MOCA-B. The secondary outcomes included auditory verbal learning test-HuaShan version (AVLT-H), shape trails test A&B (STT-A&B), animal fluence test (AFT), Boston naming test (BNT), Pittsburgh sleep quality index (PSQI), rapid eye movement sleep behavior disorder screening questionnaire (RBDSQ), Epworth sleepiness scale (ESS) and functional activities questionnaire (FAQ). These outcome measures were taken at baseline, 24 weeks later. Results: After 24 weeks of intervention, the data of 52 patients were intended for analysis. After intervention, there was significant difference in the overall scores of MoCA-B between taVNS group and sham taVNS group (p = 0.033 < 0.05). In taVNS group, compared with before intervention, the overall scores of MOCA-B increased significantly after intervention (p < 0.001). As for N5 and N7, the two sub-indicators of AVLT-H, in taVNS group, compared with before intervention, both N5 and N7 increased significantly after intervention (both ps < 0.001). As for STTB, in taVNS group, compared with before intervention, STTB was significantly reduced after intervention (p = 0.016). For BNT, in taVNS group, compared with before intervention, BNT increased significantly after intervention (p < 0.001). In taVNS group, compared with before intervention, PSQI, RBDSQ, ESS and FAQ decreased significantly after intervention (p = 0.002, 0.025, <0.001, 0.006 respectively). 1 patient with a history of tympanic membrane perforation in taVNS group was reported with mild adverse reactions which disappeared a week after termination of taVNS. The intervention of taVNS is effective on increasing the overall scores of MoCA-B, N5 and N7. Conclusion: The clinical trial demonstrated that taVNS can improve cognitive performance in patients with MCI. This inexpensive, effective and innovative method can be recommended as a therapy for more patients with MCI in the prevention or prolonging of its development into dementia, but it is still required to be further investigated. Trial registration: http://www.chictr.org.cn. (ID: ChiCTR2000038868).

Brain stimulation · randomised controlled trial · 109 citationsread the source →

Conwell Y, Van Orden KA, Stone DM, McIntosh WL, Messing S, Rowe J, Podgorski C, Kaukeinen KA, Tu X. (2021)MEDLINE-indexed journal, not yet read by usThe American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · randomised controlled trial

Peer Companionship for Mental Health of Older Adults in Primary Care: A Pragmatic, Nonblinded, Parallel-Group, Randomized Controlled Trial.

Objectives: To determine whether peer companionship delivered by an aging services agency to socially-disconnected older adult primary care patients was associated with improvement in suicidal ideation depression, anxiety, and psychological connectedness. Design: Pragmatic, nonblinded, parallel-group, randomized controlled trial comparing peer companionship, The Senior Connection (TSC), to care-as-usual (CAU). Setting: Lifespan, a nonmedical, community-based aging services agency. Participants: Adult primary care patients ages 60 years or older who endorsed feelings of loneliness or being a burden on others. Intervention: TSC was delivered by Lifespan volunteers who provided supportive visits and phone calls in the subjects' homes. CAU involved no peer companion assignment. Measurements: The primary outcome was suicidal ideation assessed by the Geriatric Suicide Ideation Scale; secondary outcomes were depression, anxiety, and feelings of belonging and being a burden on others. Data were collected at baseline, 3-, 6-, and 12-months. Results: Subjects (55% female) had a mean age of 71 years. There was no difference between groups in change in suicidal ideation or belonging. Subjects randomized to TSC had greater reduction in depression (PHQ-9; 2.33 point reduction for TSC versus 1.32 for CAU, p = 0.05), anxiety (GAD-7; TSC 1.52 versus CAU 0.28, p = 0.03), and perceived burden on others (INQ; 0.46 TSC versus 0.09 CAU, p <0.01). Conclusions: TSC was superior to CAU for improving depression, anxiety, and perceived burden, but not suicidal ideation. Although effect sizes were small, the low-cost and nationwide availability of peer companionship justify further examination of its effectiveness and scalability in improving mental health outcomes of socially disconnected older adults.

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · randomised controlled trial · 33 citationsread the source →

Schönenberg M, Wiedemann E, Schneidt A, Scheeff J, Logemann A, Keune PM, Hautzinger M. (2017)MEDLINE-indexed journal, not yet read by usThe lancet. Psychiatry · randomised controlled trial

Neurofeedback, sham neurofeedback, and cognitive-behavioural group therapy in adults with attention-deficit hyperactivity disorder: a triple-blind, randomised, controlled trial.

Background: Many studies suggest that electroencephalographic (EEG) neurofeedback might be beneficial in the treatment of attention-deficit hyperactivity disorder (ADHD). However, numbers of well controlled studies are low and neurofeedback techniques are regarded as highly controversial. The present trial examined the efficacy (compared with sham neurofeedback) and efficiency (compared with meta-cognitive therapy) of a standard EEG neurofeedback protocol in adults with ADHD. Methods: We did a concurrent, triple-blind, randomised, controlled trial using authorised deception in adults with ADHD from one centre (University of Tübingen) in Tübingen, Germany. Participants were eligible if they fulfilled the DSM-IV-TR criteria for ADHD, were aged between 18 years and 60 years, and had no or stable use of medication for at least 2 months with no intention to change. We excluded participants who had comorbid schizophrenia or schizoaffective disorder, bipolar disorder, borderline personality disorder, epilepsy, or traumatic brain injury; substance abuse or dependence; or current or planned other psychological treatment. Those eligible were randomly assigned to three groups: a neurofeedback group which received 30 verum θ-to-β neurofeedback sessions over 15 weeks, a sham neurofeedback group which received 15 sham followed by 15 verum θ-to-β neurofeedback sessions over 15 weeks, or a meta-cognitive group therapy group which received 12 sessions over 12 weeks. Participants were assigned equally to one of the three interventions through a computerised minimisation randomisation procedure stratified by sex, age, and baseline symptom severity of ADHD. Participants were masked as to whether they were receiving neurofeedback or sham neurofeedback, but those receiving meta-cognitive therapy were aware of their treatment. Clinical assessors (ie, those assessing outcomes) and research staff who did the neurofeedback training were masked to participants' randomisation status only for neurofeedback and sham neurofeedback. The primary outcome was symptom score on the Conners' adult ADHD rating scale, assessed before treatment, at midtreatment (after 8 weeks), after treatment (after 16 weeks), and 6 months later. All individuals with at least one observation after randomisation were included in the analyses. This trial is registered with ClinicalTrials.gov, number NCT01883765. Findings: Between Feb 1, 2013, and Dec 1, 2015, 761 people were assessed for eligibility. 656 (86%) were excluded and 118 (15%) were eligible for participation in this study. Eligible participants were randomly assigned to neurofeedback (38 [32%]), sham neurofeedback (39 [33%]), or meta-cognitive therapy (41 [35%]). 37 (97%) individuals for neurofeedback, 38 (97%) for sham neurofeedback, and 38 (93%) for meta-cognitive therapy were included in analyses. Self-reported ADHD symptoms decreased substantially for all treatment groups (B=-2·58 [95% CI -3·48 to -1·68]; p<0·0001) between pretreatment and the end of 6 month follow-up, independent of treatment condition (neurofeedback vs sham neurofeedback B=-0·89 [95% CI -2·14 to 0·37], p=0·168; neurofeedback vs meta-cognitive therapy -0·30 [-1·55 to 0·95], p=0·639). No treatment-related or trial-related serious adverse events were reported. Interpretation: Our findings suggest that neurofeedback training is not superior to a sham condition or group psychotherapy. All three treatments were equivalently effective in reducing ADHD symptoms. This first randomised, sham-controlled trial did not show any specific effects of neurofeedback on ADHD symptoms in adults. Funding: German Research Foundation.

The lancet. Psychiatry · randomised controlled trial · 91 citationsread the source →

Dickens AP, Richards SH, Greaves CJ, Campbell JL. (2011)MEDLINE-indexed journal, not yet read by usBMC public health · systematic review

Interventions targeting social isolation in older people: a systematic review.

Background: Targeting social isolation in older people is a growing public health concern. The proportion of older people in society has increased in recent decades, and it is estimated that approximately 25% of the population will be aged 60 or above within the next 20 to 40 years. Social isolation is prevalent amongst older people and evidence indicates the detrimental effect that it can have on health and wellbeing. The aim of this review was to assess the effectiveness of interventions designed to alleviate social isolation and loneliness in older people. Methods: Relevant electronic databases (MEDLINE, EMBASE, ASSIA, IBSS, PsycINFO, PubMed, DARE, Social Care Online, the Cochrane Library and CINAHL) were systematically searched using an extensive search strategy, for randomised controlled trials and quasi-experimental studies published in English before May 2009. Additional articles were identified through citation tracking. Studies were included if they related to older people, if the intervention aimed to alleviate social isolation and loneliness, if intervention participants were compared against inactive controls and, if treatment effects were reported. Two independent reviewers extracted data using a standardised form. Narrative synthesis and vote-counting methods were used to summarise and interpret study data. Results: Thirty two studies were included in the review. There was evidence of substantial heterogeneity in the interventions delivered and the overall quality of included studies indicated a medium to high risk of bias. Across the three domains of social, mental and physical health, 79% of group-based interventions and 55% of one-to-one interventions reported at least one improved participant outcome. Over 80% of participatory interventions produced beneficial effects across the same domains, compared with 44% of those categorised as non-participatory. Of interventions categorised as having a theoretical basis, 87% reported beneficial effects across the three domains compared with 59% of interventions with no evident theoretical foundation. Regarding intervention type, 86% of those providing activities and 80% of those providing support resulted in improved participant outcomes, compared with 60% of home visiting and 25% of internet training interventions. Fifty eight percent of interventions that explicitly targeted socially isolated or lonely older people reported positive outcomes, compared with 80% of studies with no explicit targeting. Conclusions: More, well-conducted studies of the effectiveness of social interventions for alleviating social isolation are needed to improve the evidence base. However, it appeared that common characteristics of effective interventions were those developed within the context of a theoretical basis, and those offering social activity and/or support within a group format. Interventions in which older people are active participants also appeared more likely to be effective. Future interventions incorporating all of these characteristics may therefore be more successful in targeting social isolation in older people.

BMC public health · systematic review · 395 citationsread the source →

Medication augmentation after the failure of SSRIs for depression.

Background: Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach. Methods: We randomly assigned 565 adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55 mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of remission (defined as a score of less than 6 at the end of this study) and response (a reduction in baseline scores of 50 percent or more). Results: The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P<0.009). Conclusions: Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. (ClinicalTrials.gov number, NCT00021528.).

The New England journal of medicine · randomised controlled trial · 656 citationsread the source →

Grilo CM, Masheb RM, Wilson GT. (2005)MEDLINE-indexed journal, not yet read by usBiological psychiatry · randomised controlled trial

Efficacy of cognitive behavioral therapy and fluoxetine for the treatment of binge eating disorder: a randomized double-blind placebo-controlled comparison.

Background: Cognitive behavioral therapy (CBT) and certain medications have been shown to be effective for binge eating disorder (BED), but no controlled studies have compared psychological and pharmacological therapies. We conducted a randomized, placebo-controlled study to test the efficacy of CBT and fluoxetine alone and in combination for BED. Methods: 108 patients were randomized to one of four 16-week individual treatments: fluoxetine (60 mg/day), placebo, CBT plus fluoxetine (60 mg/day) or CBT plus placebo. Medications were provided in double-blind fashion. Results: Of the 108 patients, 86 (80%) completed treatments. Remission rates (zero binges for 28 days) for completers were: 29% (fluoxetine), 30% (placebo), 55% (CBT+fluoxetine), and 73% (CBT+placebo). Intent-to-treat (ITT) remission rates were: 22% (fluoxetine), 26% (placebo), 50% (CBT+fluoxetine), and 61% (CBT+placebo). Completer and ITT analyses on remission and dimensional measures of binge eating, cognitive features, and psychological distress produced consistent findings. Fluoxetine was not superior to placebo, CBT+fluoxetine and CBT+placebo did not differ, and both CBT conditions were superior to fluoxetine and to placebo. Weight loss was modest, did not differ across treatments, but was associated with binge eating remission. Conclusions: CBT, but not fluoxetine, demonstrated efficacy for the behavioral and psychological features of BED, but not obesity.

Biological psychiatry · randomised controlled trial · 149 citationsread the source →

Kiviniemi AM, Hautala AJ, Kinnunen H, Tulppo MP. (2007)MEDLINE-indexed journal, not yet read by usEuropean journal of applied physiology · randomised controlled trial

Endurance training guided individually by daily heart rate variability measurements.

Purpose of this study was to test utility of heart rate variability (HRV) in daily endurance exercise prescriptions. Twenty-six healthy, moderately fit males were randomized into predefined training group (TRA, n = 8), HRV-guided training group (HRV, n = 9), and control group (n = 9). Four-week training period consisted of running sessions lasting 40 min each at either low- or high-intensity level. TRA group trained on 6 days a week, with two sessions at low and four at high intensity. Individual training program for HRV group was based on individual changes in high-frequency R-R interval oscillations measured every morning. Increase or no change in HRV resulted in high-intensity training on that day. If there was significant decrease in HRV (below reference value [10-day mean-SD] or decreasing trend for 2 days), low-intensity training or rest was prescribed. Peak oxygen consumption (VO(2peak)) and maximal running velocity (Load(max)) were measured in maximal treadmill test before and after the training. In TRA group, Load(max) increased from 15.1 +/- 1.3 to 15.7 +/- 1.2 km h(-1) (P = 0.004), whereas VO(2peak) did not change significantly (54 +/- 4 pre and 55 +/- 3 ml kg(-1) min(-1) post, P = 0.224). In HRV group, significant increases were observed in both Load(max) (from 15.5 +/- 1.0 to 16.4 +/- 1.0 km h(-1), P < 0.001) and VO(2peak) (from 56 +/- 4 to 60 +/- 5 ml kg(-1) min(-1), P = 0.002). The change in Load(max) was significantly greater in HRV group compared to TRA group (0.5 +/- 0.4 vs. 0.9 +/- 0.2 km h(-1), P = 0.048, adjusted for baseline values). No significant differences were observed in the changes of VO(2peak) between the groups. We concluded that cardiorespiratory fitness can be improved effectively by using HRV for daily training prescription.

European journal of applied physiology · randomised controlled trial · 193 citationsread the source →

Buchheit M, Gindre C. (2006)MEDLINE-indexed journal, not yet read by usAmerican journal of physiology. Heart and circulatory physiology · randomised controlled trial

Cardiac parasympathetic regulation: respective associations with cardiorespiratory fitness and training load.

The objective of this study was to establish the separate associations between parasympathetic modulations of the heart [evaluated through heart rate (HR) variability (HRV) indexes and postexercise HR recovery (HRR) indexes] with cardiorespiratory fitness and training load. We have measured cardiorespiratory fitness through peak oxygen consumption (Vo2 max) and estimated weekly training load with the Baecke sport score in 55 middle-aged individuals (30.8 +/- 1.8 yr, body mass index 24.5 +/- 0.4 kg/m2). HRV indexes were analyzed at rest under controlled breathing, and HRR was estimated from HR curve fitting after maximal exercise or from measurements of the number of beats recovered at 60 s after exercise. Multiple linear regressions were used to investigate the separate relationships between vagal-related HRV indexes and Vo2 max and Baecke scores. On the basis of their Vo2 max and Baecke scores, subjects were classified as fit or unfit and as low trained (LT) or moderately trained (MT), which yielded four groups: UnfitLT, UnfitMT, FitLT, and FitMT. Vagal-related HRV indexes were positively correlated with Vo2 max (P < 0.05) but not with Baecke scores. In contrast, HRR indexes were related to Baecke scores (P < 0.05) but not with Vo2 max. FitLT and FitMT had significantly higher (P < 0.05) normalized vagal-related HRV indexes than UnfitLT and UnfitMT, but HRR did not change. Moderate training was associated with significantly lower HRR indexes both in UnfitMT and FitMT compared with UnfitLT and FitLT, but there was no difference in vagal-related HRV indexes. These results indicate that vagal-related HRV indexes are related more to cardiorespiratory fitness, whereas HRR appears to be better associated with training load.

American journal of physiology. Heart and circulatory physiology · randomised controlled trial · 174 citationsread the source →

Kennedy DO, Veasey R, Watson A, Dodd F, Jones E, Maggini S, Haskell CF. (2010)MEDLINE-indexed journal, not yet read by usPsychopharmacology · randomised controlled trial

Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males.

Rationale: A significant proportion of the general population report supplementing their diet with one or more vitamins or minerals, with common reasons for doing so being to combat stress and fatigue and to improve mental functioning. Few studies have assessed the relationship between supplementation with vitamins/minerals and psychological functioning in healthy cohorts of non-elderly adults. Objectives: The present randomised, placebo-controlled, double-blind, parallel groups trial assessed the cognitive and mood effects of a high-dose B-complex vitamin and mineral supplement (Berocca(R)) in 215 males aged 30 to 55 years, who were in full-time employment. Methods: Participants attended the laboratory prior to and on the last day of a 33-day treatment period where they completed the Profile of Mood States (POMS), Perceived Stress Scale (PSS) and General Health Questionnaire (GHQ-12). Cognitive performance and task-related modulation of mood/fatigue were assessed with the 60 min cognitive demand battery. On the final day, participants also completed the Stroop task for 40 min whilst engaged in inclined treadmill walking and subsequent executive function was assessed. Results: Vitamin/mineral supplementation led to significant improvements in ratings on the PSS, GHQ-12 and the 'vigour' subscale of the POMS. The vitamin/mineral group also performed better on the Serial 3s subtractions task and rated themselves as less 'mentally tired' both pre- and post-completion of the cognitive demand battery. Conclusions: Healthy members of the general population may benefit from augmented levels of vitamins/minerals via direct dietary supplementation. Specifically, supplementation led to improved ratings of stress, mental health and vigour and improved cognitive performance during intense mental processing.

Psychopharmacology · randomised controlled trial · 108 citationsread the source →

Johansson E, Steineck G, Holmberg L, Johansson JE, Nyberg T, Ruutu M, Bill-Axelson A, SPCG-4 Investigators. (2011)MEDLINE-indexed journal, not yet read by usThe Lancet. Oncology · randomised controlled trial

Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial.

Background: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years. Methods: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint. Findings: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7-17) and a median age of 77·0 years (range 61-88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07-1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life. Interpretation: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information. Funding: US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér.

The Lancet. Oncology · randomised controlled trial · 277 citationsread the source →

Circulating microRNA changes in heart failure patients treated with cardiac resynchronization therapy: responders vs. non-responders.

Aims: MicroRNAs (miRNAs) play an important role in the pathogenesis of structural alterations of the failing heart through their ability to regulate negatively the expression levels of genes that govern the process of adaptive and maladaptive cardiac remodelling. We studied whether LV reverse remodelling after CRT was associated with changes of circulating miRNAs in patients with heart failure (HF) and dyssynchrony. Methods and results: A prospective, non-randomized self-control trial was performed in 81 patients with HF eligible for CRT. At baseline, to select the HF miRNA profile, we evaluated the expression of 84 miRNAs (implicated in the pathogenesis of structural alterations of the failing heart) in three groups of patients: healthy subjects (healthy group, n = 15); patients with HF (HF group, n = 81); and patients without HF matched for age, sex, and concomitant disease with HF patients (control group, n = 60). At 12 months, the selected miRNA profile was evaluated in plasma from responder (n = 55) and non-responder HF patients (n = 26) to CRT. In the test cohort, the HF patients were characterized by lower expression of 48 miRNAs (all P < 0.04) as compared with healthy subjects. In the validation cohort, the HF patients were characterized by lower expression of 24 miRNAs (all P < 0.03) as compared with control patients. At 12 months, 55 patients (68%) were considered responders and 26 non-responders to CRT (32%). Responders showed an increase in expression of 19 miRNAs (all P < 0.03) compared with baseline expression, whereas in the non-responders we observed an increase of six miRNAs (all P < 0.05) compared with baseline expression. At follow-up, miRNAs were differentially expressed between responders and non-responders. The responders were characterized by higher expression of five miRNAs (miRNA-26b-5p, miRNA-145-5p, miRNA-92a-3p, miRNA-30e-5p, and miRNA-29a-3p; P < 0.01 for all) as compared with non-responders. Conclusions: In responders, reverse remodelling is associated with favourable changes in miRNAs that regulate cardiac fibrosis, apoptosis, and hypertrophy.

European journal of heart failure · clinical trial · 134 citationsread the source →

Johnson NJ, Dodampahala K, Rosselot B, Perman SM, Mikkelsen ME, Goyal M, Gaieski DF, Grossestreuer AV. (2017)MEDLINE-indexed journal, not yet read by usTherapeutic hypothermia and temperature management · cohort or longitudinal

The Association Between Arterial Oxygen Tension and Neurological Outcome After Cardiac Arrest.

A number of observational studies have evaluated the association between arterial oxygen tensions and outcome after cardiac arrest with variable results. The objective of this study is to determine the association between arterial oxygen tension and neurological outcome after cardiac arrest. A retrospective cohort analysis was performed using the Penn Alliance for Therapeutic Hypothermia registry. Adult patients who experienced return of spontaneous circulation after in-hospital or out-of-hospital cardiac arrest (OHCA) and had a partial pressure of arterial oxygen (PaO2) recorded within 48 hours were included. Our primary exposure of interest was PaO2. Hyperoxemia was defined as PaO2 > 300 mmHg, hypoxemia as PaO2 < 60 mmHg, and optimal oxygenation as PaO2 60-300 mmHg. The primary outcome was neurological function at hospital discharge among survivors, as described by the cerebral performance category (CPC) score, dichotomized into "favorable" (CPCs 1-2) and "unfavorable" (CPCs 3-5). Secondary outcomes included in-hospital mortality. A total of 544 patients from 13 institutions were included. Average age was 61 years, 56% were male, and 51% were white. A total of 64% experienced OHCA, 81% of arrests were witnessed, and pulseless electrical activity was the most common initial rhythm (40%). More than 72% of the patients had cardiac etiology for their arrests, and 55% underwent targeted temperature management. A total of 38% of patients survived to hospital discharge. There was no significant association between PaO2 at any time interval and neurological outcome at hospital discharge. Hyperoxemia at 12 hours after cardiac arrest was associated with decreased odds of survival (OR 0.17 [0.03-0.89], p = 0.032). There was no significant association between arterial oxygen tension measured within the first 48 hours after cardiac arrest and neurological outcome.

Therapeutic hypothermia and temperature management · cohort or longitudinal · 34 citationsread the source →

Kelly P, John S, Vincent AL, Reed P. (2015)MEDLINE-indexed journal, not yet read by usArchives of disease in childhood · cohort or longitudinal

Abusive head trauma and accidental head injury: a 20-year comparative study of referrals to a hospital child protection team.

Aim: To describe children referred for suspected abusive head trauma (AHT) to a hospital child protection team in Auckland, New Zealand. Methods: Comparative review of demographics, histories, injuries, investigations and diagnostic outcomes for referrals under 15 years old from 1991 to 2010. Results: Records were available for 345 children. Referrals increased markedly (88 in the first decade, 257 in the second), but the diagnostic ratio was stable: AHT 60%, accidental or natural 29% and uncertain cause 11%. The probability of AHT was similar regardless of socio-economic status or ethnicity. In children under 2 years old with accidental head injuries (75/255, 29%) or AHT (180/255, 71%), characteristics of particular interest for AHT included no history of trauma (88/98, 90%), no evidence of impact to the head (84/93, 90%), complex skull fractures with intracranial injury (22/28, 79%), subdural haemorrhage (160/179, 89%) and hypoxic ischaemic injury (38/39, 97%). In children over 2 years old, these characteristics did not differ significantly between children with accidental head injuries (21/47, 45%) and AHT (26/47, 55%). The mortality of AHT was higher in children over 2 years old (10/26, 38%) than under 2 years (19/180, 11%). Conclusions: The striking increase in referrals for AHT probably represents increasing incidence. The decision to refer a hospitalised child with a head injury for assessment for possible AHT should not be influenced by socio-economic status or ethnicity. Children over 2 years old hospitalised for AHT are usually injured by mechanisms involving impact and should be considered at high risk of death.

Archives of disease in childhood · cohort or longitudinal · 63 citationsread the source →

Winzer R, Sorjonen K, Lindberg L. (2018)MEDLINE-indexed journal, not yet read by usInternational journal of environmental research and public health · cohort or longitudinal

What Predicts Stable Mental Health in the 18⁻29 Age Group Compared to Older Age Groups? Results from the Stockholm Public Health Cohort 2002⁻2014.

Mental health has decreased in young people since the 1990s, and mental health promotion is an urgent matter. A first step is to identify which social determinants could be of importance for intervention. We used the Stockholm Public Health Cohort, a longitudinal population-based health survey, completed by 31,000 inhabitants in the Stockholm County. We focused on the 18⁻29 age group, n = 3373 (60% females, 40% males) and aimed at assessing which social determinants predict stable mental health, measured as scoring <3 points on the General Health Questionnaire 12 at all time points: 2002, 2007, 2010, and 2014. Forty-six percent of males and 36% of females reported stable mental health. Among the 17 predictors on sociodemographics, socioeconomics, social capital, health behavior, and victimization, six predicted stable mental health in the following order: occupation and especially employment, emotional support, male gender, being born in Sweden, absence of financial strain, and consumption of fruit and berries. In the 30⁻84 age group, 66% males and 55% females reported stable mental health. Nine determinants in the following rank predicted stable mental health: absence of financial strain, occupation and especially being self-employed, emotional support, male gender, physical activity, instrumental support, interpersonal trust, community trust, and absence of hazardous alcohol consumption. Interaction analysis showed significant difference between the younger and older group regarding physical activity and absence of financial strain with importance being higher for the older group. Our findings indicate that the determinants of health differ across the life-course with fewer predictors related to social capital and health behavior in the younger group compared to the older. We conclude that health-promoting interventions should be lifespan-sensitive.

International journal of environmental research and public health · cohort or longitudinal · 13 citationsread the source →

Sippel C, Kim Y, Wallau A, Brossart P, Schmidt-Wolf I, Walger P. (2015)MEDLINE-indexed journal, not yet read by usJournal of cancer research and clinical oncology

AML versus ICU: outcome of septic AML patients in an intensive care setting.

Purpose: Intensive therapy regimens in patients with acute myeloid leukemia (AML) frequently result in sepsis and septic shock. In this study, we investigated the prognostic outcome of AML patients requiring intensive care treatment due to severe sepsis or septic shock. Design: We present a retrospective cohort study in a medical intensive care unit (ICU) of a university hospital that serves as a tertiary care center. Materials and methods: Here we present data from 44 AML patients of our ICU with 29 requiring invasive mechanical ventilation due to sepsis and compared multiple clinical and laboratory parameters of ICU survivors and non-survivors. Results: Mean age was 59.5 years, the overall mortality rate was 41% (18/44), and the mortality rate among patients who received mechanical ventilation was 55% (16/29). The mortality rate among younger patients (aged 60 years or less) was 17% (3/18), while 58% of the older patients died (15/26). The mortality rate among younger patients who received mechanical ventilation was 23% (3/13) compared with 81% (13/16) of the older patients. The mean invasive ventilation time was 415 h in non-survivors compared with 667 h in survivors. No differences could be identified between survivors and non-survivors, concerning multiple laboratory parameters or AML prognostic and therapeutic parameters; our analysis, however, confirmed a statistically significant difference in the patients' age. Conclusions: In previous studies, age was one of the most important prognostic factors in AML patients receiving mechanical ventilation due to severe sepsis or septic shock. In spite of improvements in diagnostic and treatment over the last couple of years, our study indicates that this fact still is true. However, the overall outcome has improved over the years due to improvements in intensive care medicine.

Journal of cancer research and clinical oncology · 14 citationsread the source →

Lindmark U, Stenström U, Gerdin EW, Hugoson A. (2010)MEDLINE-indexed journal, not yet read by usScandinavian journal of public health · cohort or longitudinal

The distribution of ''sense of coherence'' among Swedish adults: a quantitative cross-sectional population study.

Background: Antonovsky's concept of ''sense of coherence'' (SOC) has been shown to be related to health. The aim of this study was to describe the distribution of SOC scores and their components in an adult Swedish population aged 20-80 years. Methods: A random sample of 910 individuals from Jönköping, Sweden, aged 20, 30, 40, 50, 60, 70 and 80 years, of which 589 agreed to participate in an oral health examination. The participants answered Antonovsky's 13-item version of ''the life orientation questionnaire scale''. The response to the items and the distribution of the three components of comprehensibility, manageability and meaningfulness were analyzed for different age groups and genders using mean values and standard deviations, Student's t-test and ANOVA. Results: A total of 526 individuals, 263 men and 263 women, answered all 13 questions and constituted the final material for the study (response rate 89%). The individual SOC score increased with age. The 20 year olds had a statistically significantly lower SOC score compared with the other age groups and 55% of them had a low SOC (< or = 66 points) compared with 17% of the 80 year olds. Men in the 60 and 70 year age groups had a statistically significantly higher SOC score compared with women of the same age. Conclusions: The individual distribution of SOC varied with age and gender. Twenty year olds had a significantly lower SOC score compared with elderly age groups. Elderly men had a statistically significantly higher SOC score compared with women of the same age.

Scandinavian journal of public health · cohort or longitudinal · 60 citationsread the source →

Campbell HA, Akerman AP, Kissling LS, Prout JR, Gibbons TD, Thomas KN, Cotter JD. (2022)MEDLINE-indexed journal, not yet read by usExperimental physiology

Acute physiological and psychophysical responses to different modes of heat stress.

New findings: What is the central question of this study? What are the profiles of acute physiological and psychophysical strain during and in recovery from different modes of heating, and to what extent do these diminish after repeated exposure? What is the main finding and its importance? Mode of heating affects the strain profiles during heat stress and recovery. Exercise in the heat incurred the greatest cardiovascular strain during heating and recovery. Humid heat was poorly tolerated despite heat strain being no greater than in other heating modes, and tolerance did not improve with multiple exposures. Abstract: Heat stress is common and arises endogenously and exogenously. It can be acutely hazardous while also increasingly advocated to drive health and performance-related adaptations. Yet, the nature of strain (deviation in regulated variables) imposed by different heating modes is not well established, despite the potential for important differences. We, therefore, compared three modes of heat stress for thermal, cardiovascular and perceptual strain profiles during exposure and recovery when experienced as a novel stimulus and an accustomed stimulus. In a crossover design, 13 physically active participants (five females) underwent 5 days of 60-min exposures to hot water immersion (40°C), sauna (55°C, 54% relative humidity) and exercise in the heat (40°C, 52% relative humidity), and a thermoneutral water immersion control (36.5°C), each separated by ≥4 weeks. Physiological (thermal, cardiovascular, haemodynamic) and psychophysical strain responses were assessed on days 1 and 5. Sauna evoked the warmest skin (40°C; P < 0.001) but exercise in the heat caused the largest increase in core temperature, sweat rate, heart rate (post hoc comparisons all P < 0.001) and systolic blood pressure (P ≤ 0.002), and possibly decrease in diastolic blood pressures (P ≤ 0.130), regardless of day. Thermal sensation and feeling state were more favourable on day 5 than on day 1 (P ≤ 0.021), with all modes of heat being equivalently uncomfortable (P ≥ 0.215). Plasma volume expanded the largest extent during immersions (P < 0.001). The current data highlight that exercising in the heat generates a more complex strain profile, while passive heat stress in humid heat has lower tolerance and more cardiovascular strain than hot water immersion.

Experimental physiology · 26 citationsread the source →

Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge.

Background: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. Methods: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. Findings: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044). Interpretation: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. Funding: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.

EClinicalMedicine · 441 citationsread the source →

Bjørkløf GH, Engedal K, Selbæk G, Kouwenhoven SE, Helvik AS. (2013)MEDLINE-indexed journal, not yet read by usDementia and geriatric cognitive disorders · review

Coping and depression in old age: a literature review.

Background/aims: The interest in the relation between coping and depression in older persons is growing, but research on the concepts and instruments of coping in relation to depression among older persons is scarce and systematic reviews are lacking. With this background, we wanted to gain a systematic overview of this field by performing a systematic literature search. Methods: A computer-aided search in MEDLINE, CINAHL, PsycINFO, Embase, PubMed and www.salutogenesis.fi was conducted. We systematically searched for studies including coping and depression among persons 60 years of age and above. The included studies were evaluated according to predefined quality criteria. Results: Seventy-five studies, 38 clinical and 37 community settings, were included. Of these, 44 were evaluated to be of higher quality. Studies recruiting samples of older persons with a major depressive disorder, moderate or severe cognitive impairment or those who were dependent on care were scarce, thus the research is not representative of such samples. We found a huge variety of instruments assessing resources and strategies of coping (55 inventories). Although we found the relation between resources and strategies of coping and depression to be strong in the majority of studies, i.e. a higher sense of control and internal locus of control, more active strategies and positive religious coping were significantly associated with fewer symptoms of depression both in longitudinal and cross-sectional studies in clinical and community settings. Conclusion: Resources and strategies of coping are significantly associated with depressive symptoms in late life, but more research to systematize the field of coping and to validate the instruments of resources and strategies of coping in older populations is required, especially among older persons suffering from major depression and cognitive decline.

Dementia and geriatric cognitive disorders · review · 77 citationsread the source →

L. Pinède; P. Duhaut; R Loire (2001)MEDLINE-indexed journal, not yet read by usMedicine · review

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 →

Robert Barnhart; Mary Jo Davenport; Susan Epps; Vey M. Nordquist (2003)MEDLINE-indexed journal, not yet read by usPhysical Therapy · review

Developmental Coordination Disorder

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

Physical Therapy · review · 472 citationsread the source →

Peter J. Barnes; Ian M. Adcock (2003)MEDLINE-indexed journal, not yet read by usAnnals of Internal Medicine · review

How Do Corticosteroids Work in Asthma?

Reviews2 September 2003How Do Corticosteroids Work in Asthma?Peter J. Barnes, DM, DSc and Ian M. Adcock, PhDPeter J. Barnes, DM, DScFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this author and Ian M. Adcock, PhDFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-5_Part_1-200309020-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesAsthma is the most common chronic disease in westernized countries. Patients with asthma have an underlying chronic inflammation of the airways characterized by activated mast cells, eosinophils, and T-helper 2 lymphocytes. This results in increased responsiveness of the airways to such triggers as exercise, allergens, and air pollutants. This chronic inflammation underlies the typical symptoms of asthma, which include intermittent wheezing, coughing, shortness of breath, and chest tightness. Corticosteroids are the most effective treatment for asthma, and inhaled corticosteroids have become first-line treatment for children and adults with persistent symptoms. Corticosteroids suppress the chronic airway inflammation in patients with asthma, and the molecular ...References1. Busse WW, Lemanske RF. Asthma. N Engl J Med. 2001;344:350-62. [PMID: 11172168] CrossrefMedlineGoogle Scholar2. Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998;50:515-96. [PMID: 9860804] MedlineGoogle Scholar3. Barnes PJ, Adcock IM. Transcription factors and asthma. Eur Respir J. 1998;12:221-34. [PMID: 9701442] CrossrefMedlineGoogle Scholar4. Hart LA, Krishnan VL, Adcock IM, Barnes PJ, Chung KF. Activation and localization of transcription factor, nuclear factor-B, in asthma. Am J Respir Crit Care Med. 1998;158:1585-92. [PMID: 9817712] CrossrefMedlineGoogle Scholar5. Barnes PJ, Karin M. Nuclear factor-B: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med. 1997;336:1066-71. [PMID: 9091804] CrossrefMedlineGoogle Scholar6. Donovan CE, Mark DA, He HZ, Liou HC, Kobzik L, Wang Y, . NF-kappa B/Rel transcription factors: c-Rel promotes airway hyperresponsiveness and allergic pulmonary inflammation. J Immunol. 1999;163:6827-33. [PMID: 10586083] MedlineGoogle Scholar7. Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell. 1996;87:953-9. [PMID: 8945521] CrossrefMedlineGoogle Scholar8. Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Annu Rev Biochem. 2001;70:81-120. [PMID: 11395403] CrossrefMedlineGoogle Scholar9. Ito K, Barnes PJ, Adcock IM. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol. 2000;20:6891-903. [PMID: 10958685] CrossrefMedlineGoogle Scholar10. Gao L, Cueto MA, Asselbergs F, Atadja P. Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem. 2002;277:25748-55. [PMID: 11948178] CrossrefMedlineGoogle Scholar11. Ito K, Caramori G, Lim S, Oates T, Chung KF, Barnes PJ, . Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med. 2002;166:392-6. [PMID: 12153977] CrossrefMedlineGoogle Scholar12. Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms [Editorial]. Clin Sci (Lond). 1998;94:557-72. [PMID: 9854452] CrossrefMedlineGoogle Scholar13. Barnes PJ. Molecular mechanisms of corticosteroids in allergic diseases. Allergy. 2001;56:928-36. [PMID: 11576070] CrossrefMedlineGoogle Scholar14. Schwiebert LM, Stellato C, Schleimer RP. The epithelium as a target of glucocorticoid action in the treatment of asthma. Am J Respir Crit Care Med. 1996; 154:S16-9; discussion S19-20. [PMID: 8756782] Google Scholar15. Herrscher RF, Kasper C, Sullivan TJ. Endogenous cortisol regulates immunoglobulin E-dependent late phase reactions. J Clin Invest. 1992;90:596-603. [PMID: 1644926] CrossrefMedlineGoogle Scholar16. Barnes PJ. Therapeutic strategies for allergic diseases. Nature. 1999;402:B31-8. [PMID: 10586893] CrossrefMedlineGoogle Scholar17. Yudt MR, Cidlowski JA. The glucocorticoid receptor: coding a diversity of proteins and responses through a single gene. Mol Endocrinol. 2002;16:1719-26. [PMID: 12145329] CrossrefMedlineGoogle Scholar18. Leung DY, Hamid Q, Vottero A, Szefler SJ, Surs W, Minshall E, . Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor . J Exp Med. 1997;186:1567-74. [PMID: 9348314] CrossrefMedlineGoogle Scholar19. Hecht K, Carlstedt-Duke J, Stierna P, Gustaffson J, Bronnegard M, Wilkstrom AC. Evidence that the -isoform of the human glucocorticoid receptor does not act as a physiologically significant repressor. J Biol Chem. 1997;272:26659-64. [PMID: 9334248] CrossrefMedlineGoogle Scholar20. Bodwell JE, Webster JC, Jewell CM, Cidlowski JA, Hu JM, Munck A. Glucocorticoid receptor phosphorylation: overview, function and cell cycle-dependence. J Steroid Biochem Mol Biol. 1998;65:91-9. [PMID: 9699861] CrossrefMedlineGoogle Scholar21. Reichardt HM, Kaestner KH, Tuckermann J, Kretz O, Wessely O, Bock R, . DNA binding of the glucocorticoid receptor is not essential for survival. Cell. 1998;93:531-41. [PMID: 9604929] CrossrefMedlineGoogle Scholar22. Ito K, Jazrawi E, Cosio B, Barnes PJ, Adcock IM. p65-activated histone acetyltransferase activity is repressed by glucocorticoids: mifepristone fails to recruit HDAC2 to the p65-HAT complex. J Biol Chem. 2001;276:30208-15. [PMID: 11395507] CrossrefMedlineGoogle Scholar23. Yao TP, Ku G, Zhou N, Scully R, Livingston DM. The nuclear hormone receptor coactivator SRC-1 is a specific target of p300. Proc Natl Acad Sci U S A. 1996;93:10626-31. [PMID: 8855229] CrossrefMedlineGoogle Scholar24. Kurihara I, Shibata H, Suzuki T, Ando T, Kobayashi S, Hayashi M, . Expression and regulation of nuclear receptor coactivators in glucocorticoid action. Mol Cell Endocrinol. 2002;189:181-9. [PMID: 12039076] CrossrefMedlineGoogle Scholar25. Hall SE, Lim S, Witherden IR, Tetley TD, Barnes PJ, Kamal AM, . Lung type II cell and macrophage annexin I release: differential effects of two glucocorticoids. Am J Physiol. 1999;276:L114-21. [PMID: 9887063] MedlineGoogle Scholar26. Newton R, Hart LA, Stevens DA, Bergmann M, Donnelly LE, Adcock IM, . Effect of dexamethasone on interleukin-1beta-(IL-1)-induced nuclear factor-B (NF-B) and B-dependent transcription in epithelial cells. Eur J Biochem. 1998;254:81-9. [PMID: 9652398] CrossrefMedlineGoogle Scholar27. Heck S, Bender K, Kullmann M, Gottlicher M, Herrlich P, Cato AC. IB-independent downregulation of NF-B activity by glucocorticoid receptor. EMBO J. 1997;16:4698-707. [PMID: 9303314] CrossrefMedlineGoogle Scholar28. Reichardt HM, Tuckermann JP, Gottlicher M, Vujic M, Weih F, Angel P, . Repression of inflammatory responses in the absence of DNA binding by the glucocorticoid receptor. EMBO J. 2001;20:7168-73. [PMID: 11742993] CrossrefMedlineGoogle Scholar29. Hart L, Lim S, Adcock I, Barnes PJ, Chung KF. Effects of inhaled corticosteroid therapy on expression and DNA-binding activity of nuclear factor B in asthma. Am J Respir Crit Care Med. 2000;161:224-31. [PMID: 10619824] CrossrefMedlineGoogle Scholar30. Imhof A, Wolffe AP. Transcription: gene control by targeted histone acetylation. Curr Biol. 1998;8:R422-4. [PMID: 9637914] CrossrefMedlineGoogle Scholar31. Peterson CL. HDAC's at work: everyone doing their part. Mol Cell. 2002;9:921-2. [PMID: 12049726] CrossrefMedlineGoogle Scholar32. Berger SL. An embarrassment of niches: the many covalent modifications of histones in transcriptional regulation. Oncogene. 2001;20:3007-13. [PMID: 11420715] CrossrefMedlineGoogle Scholar33. Bannister AJ, Schneider R, Kouzarides T. Histone methylation: dynamic or static? Cell. 2002;109:801-6. [PMID: 12110177] CrossrefMedlineGoogle Scholar34. Kagoshima M, Wilcke T, Ito K, Tsaprouni L, Barnes PJ, Punchard N, . Glucocorticoid-mediated transrepression is regulated by histone acetylation and DNA methylation. Eur J Pharmacol. 2001;429:327-34. [PMID: 11698053] CrossrefMedlineGoogle Scholar35. Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293:1074-80. [PMID: 11498575] CrossrefMedlineGoogle Scholar36. Bergmann M, Barnes PJ, Newton R. Molecular regulation of granulocyte macrophage colony-stimulating factor in human lung epithelial cells by interleukin (IL)-1, IL-4, and IL-13 involves both transcriptional and post-transcriptional mechanisms. Am J Respir Cell Mol Biol. 2000;22:582-9. [PMID: 10783130] CrossrefMedlineGoogle Scholar37. Caelles C, Gonzalez-Sancho JM, Munoz A. Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 1997;11:3351-64. [PMID: 9407028] CrossrefMedlineGoogle Scholar38. Vanden Berghe W, Vermeulen L, De Wilde G, De Bosscher K, Boone E, Haegeman G. Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol. 2000;60:1185-95. [PMID: 11007957] CrossrefMedlineGoogle Scholar39. Lasa M, Brook M, Saklatvala J, Clark AR. Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. Mol Cell Biol. 2001;21:771-80. [PMID: 11154265] CrossrefMedlineGoogle Scholar40. Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR. Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38. Mol Cell Biol. 2002;22:7802-11. [PMID: 12391149] CrossrefMedlineGoogle Scholar41. Barnes PJ. Scientific rationale for inhaled combination therapy with long-acting 2-agonists and corticosteroids. Eur Respir J. 2002;19:182-91. [PMID: 11843317] CrossrefMedlineGoogle Scholar42. Adcock IM, Stevens DA, Barnes PJ. Interactions of glucocorticoids and 2-agonists. Eur Respir J. 1996;9:160-8. [PMID: 8834349] CrossrefMedlineGoogle Scholar43. Mak JC, Nishikawa M, Shirasaki H, Miyayasu K, Barnes PJ. Protective effects of a glucocorticoid on downregulation of pulmonary 2-adrenergic receptors in vivo. J Clin Invest. 1995;96:99-106. [PMID: 7615841] CrossrefMedlineGoogle Scholar44. Mak JC, Hisada T, Salmon M, Barnes PJ, Chung KF. Glucocorticoids reverse IL-1-induced impairment of -adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinases. Br J Pharmacol. 2002;135:987-96. [PMID: 11861327] CrossrefMedlineGoogle Scholar45. Eickelberg O, Roth M, Lorx R, Bruce V, Rudiger J, Johnson M, . Ligand-independent activation of the glucocorticoid receptor by 2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem. 1999;274:1005-10. [PMID: 9873044] CrossrefMedlineGoogle Scholar46. Pang L, Knox AJ. Regulation of TNF--induced eotaxin release from cultured human airway smooth muscle cells by 2-agonists and corticosteroids. FASEB J. 2001;15:261-269. [PMID: 11149914] CrossrefMedlineGoogle Scholar47. Korn SH, Wouters EF, Wesseling G, Arends JW, Thunnissen FB. Interaction between glucocorticoids and 2-agonists: and glucocorticoid-receptor mRNA expression in human bronchial epithelial cells. Biochem Pharmacol. 1998;56:1561-9. [PMID: 9973176] CrossrefMedlineGoogle Scholar48. Usmani OS, Maneechotesuwan K, Adcock IM, Barnes PJ. Glucocorticoid receptor activation following inhaled fluticasone and salmeterol [Abstract]. Am J Respir Crit Care Med. 2002;165:A616. Google Scholar49. Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med. 2003;167:813-8. [PMID: 12623857] CrossrefMedlineGoogle Scholar50. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, . A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci U S A. 2002;99:8921-6. [PMID: 12070353] CrossrefMedlineGoogle Scholar51. Evans DJ, Taylor DA, Zetterstrom O, Chung KF, O'Connor BJ, Barnes PJ. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med. 1997;337:1412-8. [PMID: 9358138] CrossrefMedlineGoogle Scholar52. Ukena D, Harnest U, Sakalauskas R, Magyar P, Vetter N, Steffen H, . Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma. Eur Respir J. 1997;10:2754-60. [PMID: 9493656] CrossrefMedlineGoogle Scholar53. Lim S, Jatakanon A, Gordon D, Macdonald C, Chung KF, Barnes PJ. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice. Thorax. 2000;55:837-41. [PMID: 10992535] CrossrefMedlineGoogle Scholar54. Szefler SJ, Leung DY. Glucocorticoid-resistant asthma: pathogenesis and clinical implications for management. Eur Respir J. 1997;10:1640-7. [PMID: 9230260] CrossrefMedlineGoogle Scholar55. Barnes PJ. Steroid-resistant asthma. Eur Resp Rev. 2000;10:74-8. Google Scholar56. Spahn JD, Szefler SJ, Surs W, Doherty DE, Nimmagadda SR, Leung DY. A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity. J Immunol. 1996;157:2654-9. [PMID: 8805670] MedlineGoogle Scholar57. Irusen E, Matthews JG, Takahashi A, Barnes PJ, Chung KF, Adcock IM. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol. 2002;109:649-57. [PMID: 11941315] CrossrefMedlineGoogle Scholar58. Hamid QA, Wenzel SE, Hauk PJ, Tsicopoulos A, Wallaert B, Lafitte JJ, . Increased glucocorticoid receptor in airway cells of glucocorticoid-insensitive asthma. Am J Respir Crit Care Med. 1999;159:1600-4. [PMID: 10228133] CrossrefMedlineGoogle Scholar59. Gagliardo R, Chanez P, Vignola AM, Bousquet J, Vachier I, Godard P, . Glucocorticoid receptor and in glucocorticoid dependent asthma. Am J Respir Crit Care Med. 2000;162:7-13. [PMID: 10903212] CrossrefMedlineGoogle Scholar60. Corrigan CJ, Brown PH, Barnes NC, Szefler SJ, Tsai JJ, Frew AJ, . Glucocorticoid resistance in chronic asthma. Glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics, and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro. Am Rev Respir Dis. 1991;144:1016-25. [PMID: 1952426] CrossrefMedlineGoogle Scholar61. Adcock IM, Lane SJ, Brown CR, Lee TH, Barnes PJ. Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma. J Exp Med. 1995;182:1951-8. [PMID: 7500041] CrossrefMedlineGoogle Scholar62. Matthews JG, Ito K, Barnes PJ, Adcock IM. Corticosteroid-resistant and corticosteroid-dependent asthma: two clinical phenotypes can be associated with the same in vitro defects in nuclear translocation and acetylation of histone 4 [Abstract]. Am J Respir Crit Care Med. 2000;161:A189. Google Scholar63. Keatings VM, Jatakanon A, Worsdell YM, Barnes PJ. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997;155:542-8. [PMID: 9032192] CrossrefMedlineGoogle Scholar64. Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:1635-9. [PMID: 10556133] CrossrefMedlineGoogle Scholar65. Nightingale JA, Rogers DF, Fan Chung K, Barnes PJ. No effect of inhaled budesonide on the response to inhaled ozone in normal subjects. Am J Respir Crit Care Med. 2000;161:479-86. [PMID: 10673189] CrossrefMedlineGoogle Scholar66. Culpitt SV, Rogers DF, Shah P, De Matos C, Russell RE, Donnelly LE, . Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:24-31. [PMID: 12406856] CrossrefMedlineGoogle Scholar67. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J. 2001;15:1110-2. [PMID: 11292684] CrossrefMedlineGoogle Scholar68. Ito K, Watanabe S, Kharitonov S, Hanazawa T, Adcock IM, Barnes PJ. Histone deacetylase activity and gene expression in COPD patients [Abstract]. Eur Respir J. 2001;18:316S. MedlineGoogle Scholar69. Montuschi P, Collins JV, Ciabattoni G, Lazzeri N, Corradi M, Kharitonov SA, . Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000;162:1175-7. [PMID: 10988150] CrossrefMedlineGoogle Scholar70. Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids. New developments. Am J Respir Crit Care Med. 1998;157:S1-53. [PMID: 9520807] CrossrefMedlineGoogle Scholar71. Heck S, Kullmann M, Gast A, Ponta H, Rahmsdorf HJ, Herrlich P, . A distinct modulating domain in glucocorticoid receptor monomers in the repression of activity of the transcription factor AP-1. EMBO J. 1994;13:4087-95. [PMID: 8076604] CrossrefMedlineGoogle Scholar72. Adcock IM, Nasuhara Y, Stevens DA, Barnes PJ. Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-B and lack of I-B involvement. Br J Pharmacol. 1999;127:1003-11. [PMID: 10433509] CrossrefMedlineGoogle Scholar73. Vayssiere BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, . Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol. 1997;11:1245-55. [PMID: 9259316] CrossrefMedlineGoogle Scholar74. Belvisi MG, Wicks SL, Battram CH, Bottoms SE, Redford JE, Woodman P, . Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity. J Immunol. 2001;166:1975-82. [PMID: 11160246] CrossrefMedlineGoogle Scholar75. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, . Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell. 2002;110:93-105. [PMID: 12151000] CrossrefMedlineGoogle Scholar76. Barnes PJ. New treatments for COPD. Nat Rev Drug Discov. 2002;1:437-46. [PMID: 12119745] CrossrefMedlineGoogle Scholar77. Ito K, Lim S, Chung KF, Barnes PJ, Adcock IM. Theophylline enhances histone deacetylase activity and restores glucocorticoid function during oxidative stress [Abstract]. Am J Respir Crit Care Med. 2002;165:A625. Google Scholar Author, Article, and Disclosure InformationAffiliations: From National Heart and Lung Institute, Imperial College, London, United Kingdom. Disclosures:Grants received: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca); Grants pending: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca).Corresponding Author: P.J. Barnes, DM, DSc, Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom; e-mail, p.j.[email protected]ac.uk. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNanotechnology based advanced therapeutic strategies for targeting interleukins in chronic respiratory diseasesLipopolysaccharide Regulates Pro- and Anti-Inflammatory Cytokines, Corticosterone, and Melatonin in ToadsThe central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to interventionAsthma and COVID-19: Emphasis on Adequate of as of and as a Effect of the resistance in asthma: and molecular effects of on a of allergic between and and gene expression of glucocorticoid and receptors from the for of human respiratory with glucocorticoids in the treatment of asthma: of the oral corticosteroids and persistent in from the asthma to bronchial asthma as for A of of Melatonin and Glucocorticoid with in the a between Melatonin and of in Steroid Drug by of proteins during the Efficacy of to in a of corticosteroids in asthma: the between and the novel mode of action of the Association and 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Annals of Internal Medicine · review · 370 citationsread the source →

Brehmer Y, Westerberg H, Bäckman L. (2012)MEDLINE-indexed journal, not yet read by usFrontiers in human neuroscience

Working-memory training in younger and older adults: training gains, transfer, and maintenance.

Working memory (WM), a key determinant of many higher-order cognitive functions, declines in old age. Current research attempts to develop process-specific WM training procedures, which may lead to general cognitive improvement. Adaptivity of the training as well as the comparison of training gains to performance changes of an active control group are key factors in evaluating the effectiveness of a specific training program. In the present study, 55 younger adults (20-30 years of age) and 45 older adults (60-70 years of age) received 5 weeks of computerized training on various spatial and verbal WM tasks. Half of the sample received adaptive training (i.e., individually adjusted task difficulty), whereas the other half-worked on the same task material but on a low task difficulty level (active controls). Performance was assessed using criterion, near-transfer, and far-transfer tasks before training, after 5 weeks of intervention, as well as after a 3-month follow-up interval. Results indicate that (a) adaptive training generally led to larger training gains than low-level practice, (b) training and transfer gains were somewhat greater for younger than for older adults in some tasks, but comparable across age groups in other tasks, (c) far-transfer was observed to a test on sustained attention and for a self-rating scale on cognitive functioning in daily life for both young and old, and (d) training gains and transfer effects were maintained across the 3-month follow-up interval across age.

Frontiers in human neuroscience · 228 citationsread the source →

Wu S, Renzaho AMN, Hall BJ, Shi L, Ling L, Chen W. (2021)MEDLINE-indexed journal, not yet read by usThe lancet. Psychiatry

Time-varying associations of pre-migration and post-migration stressors in refugees' mental health during resettlement: a longitudinal study in Australia.

Background: Understanding the time-varying association of pre-migration and post-migration stressors in refugees' mental health could help in designing tailored health promotion services at different resettlement stages and improving the efficiency of resource allocation. In this study, we explored these time-varying associations. Methods: We used data from the first four waves (October, 2013, to February, 2017) of a national refugee-based longitudinal study, the Building a New Life in Australia (BNLA) project. Post-traumatic stress disorder (PTSD) and high risk of severe mental illness (HR-SMI) were used to assess mental health. The independent variables included the number of potentially traumatic events experienced during the pre-migration process, and a range of post-migration stressors. We used logistic regression models to analyse the relative importance of variables and time-varying associations between the pre-migration potentially traumatic events, post-migration resettlement stressors, and refugees' mental health. Analyses were stratified by gender, and sociodemographic covariates included age, marital status, education level, country of birth, and weekly income. Results: 2399 participants were surveyed in Wave 1 of the BNLA project in 2013-14, of whom 2009 (83·7%) responded in Wave 2 in 2014-15, 1894 (78·9%) in Wave 3 in 2015-16, and 1929 (80·4%) in Wave 4 in 2016-17. The three most important factors associated with mental health in each wave differed for male and female refugees, but the socioeconomic stressors of loneliness and adjustment to life in Australia were consistently prominent. Positive associations between socioeconomic stressors and mental ill-health were found for both genders, with a peak at Wave 2 (adjusted odds ratio [AOR] among men, 1·60 [95% CI 1·26-2·03], p=0.0001 for PTSD; AOR 1·86 [1·35-2·55], p=0·0001 for HR-SMI; and among women, AOR 1·81 [1·27-2·57], p=0·0009 for PTSD; AOR 2·24 [1·49-3·38], p=0·0001 for HR-SMI). Associations between loneliness and mental health fluctuated, but were significant for both genders in Wave 4 (among men, AOR 1·90 [1·21-2·99], p=0·0051 for PTSD; AOR 3·70 [2·18-6·27], p<0·0001 for HR-SMI; and among women, AOR 3·65 [2·08-6·39], p<0·0001 for PTSD; AOR 3·68 [2·02-6·69], p<0·0001 for HR-SMI). The association between difficulties in adjustment to life in Australia and male refugees' mental ill-health increased continuously during the resettlement period. Interpretation: Gender-specific and time-sensitive services should be considered to improve refugees' mental health. For both genders, improved economic conditions that complement social security benefits deserve attention and are relevant throughout the resettlement process. At the later stage of resettlement, services to reduce loneliness could be carried out, and reducing stressors related to adjustment to life in the host country is especially needed for male refugees. Funding: None.

The lancet. Psychiatry · 63 citationsread the source →

Nuzum D, Meaney S, O'Donoghue K. (2016)MEDLINE-indexed journal, not yet read by usBMJ supportive & palliative care

The provision of spiritual and pastoral care following stillbirth in Ireland: a mixed methods study.

Background: The death of a baby is recognised as one of the most difficult bereavements with life-long impact for parents. How bereaved parents are cared for influences their grief journey. Optimal holistic care is provided when the physical, emotional, spiritual and social needs of parents are attended to. This study reviewed how spiritual care is provided to bereaved parents following stillbirth in maternity units in Ireland and the impact of stillbirth on healthcare chaplains. Methods: This was a mixed methods study using semistructured qualitative interviews with hospital chaplains in Irish maternity units. Quantitative data about the provision of services to bereaved parents were collated from the interviews. Qualitative data were analysed thematically to identify key themes. Results: 20 chaplains from 17 units participated in the study (85% of Irish maternity units). 12 chaplains (60%) are formally accredited chaplains; only one has received specialist training in perinatal bereavement care. 11 chaplains (55%) provide follow-up bereavement care. Seven chaplains (35%) did not feel part of the multidisciplinary team. The main themes that emerged were the impact of stillbirth, suffering and the challenge to faith creating inner conflict and doubt. Conclusions: The provision of spiritual care following stillbirth in Ireland is diverse. Spiritual care in this specialised area by chaplains who are not professionally trained and accredited potentially impacts quality and depth of care. Chaplains experience considerable impact and challenge to personal faith and belief as they provide care. Recommendations are made for ongoing education and greater support for chaplains.

BMJ supportive & palliative care · 11 citationsread the source →

Soriani N, Trevisi E, Calamari L. (2012)MEDLINE-indexed journal, not yet read by usJournal of animal science

Relationships between rumination time, metabolic conditions, and health status in dairy cows during the transition period.

The main objective of this experiment was to monitor the rumination pattern during the transition period in primiparous (PR) and pluriparous (PL) dairy cows and to investigate its relationships with metabolic conditions, milk yield, and health status. The study was carried out in an experimental free-stall barn and involved 32 Italian Friesian cows (9 PR and 23 PL) during the transition phase. The rumination time (RT) was recorded with an automatic system (HR-Tag), and data were calculated and summarized in 2-h intervals. Blood samples were collected during the transition phase to assess biochemical variables related to energy, protein, and mineral metabolism, as well as markers of inflammatory conditions and some enzyme activity. Daily milk yield, BW, nutritional condition, and health status were also recorded. The average RT before calving (-20 to -6 d) was 463 min/d in PR (range 270 to 620) and 522 min/d in PL (range 411 to 640). In the early lactation [15 to 40 d in milk (DIM)], the average RT was 504 min/d in PR (range 400 to 585) and 562 min/d in PL (range 414 to 685) and was positively correlated with milk yield (r = 0.36; P < 0.001). The RT reached the minimum at calving d (262 min/d in PR and 278 min/d in PL). Before calving the percentage of RT during the nighttime was 60% in PR and 62% in PL, whereas the values decreased after calving (55% in PR and 57% in PL). During the first weeks of lactation, PR showed a shorter RT than PL in the 2-h intervals that included milkings. Cows with reduced RT before calving maintained reduced RT after calving and suffered a greater frequency of disease than cows with greater RT in late pregnancy. Moreover, cows characterized by mild inflammatory conditions and without health disorders or only mild health disorders during the puerperium showed a greater average rumination time (over 520 min/d) during the first 10 d of lactation. Conversely, the decreased RT (450 min/d) during the first few days of lactation was observed in cows with subclinical diseases or health disorders. Cows affected by clinical mastitis during the trial showed a reduction of RT and a change in its variability already some days before the drug treatment. Our results suggest that the automatic measurement of RT is useful to predict calving time and to quickly obtain information on health status of the animals in a period as critical as the transition phase.

Journal of animal science · 123 citationsread the source →

Pollini RA, Paquette CE, Drvar T, Marshalek P, Ang-Rabanes M, Feinberg J, Haut MW. (2021)MEDLINE-indexed journal, not yet read by usThe International journal on drug policy

A qualitative assessment of discharge against medical advice among patients hospitalized for injection-related bacterial infections in West Virginia.

Background: The incidence of infective endocarditis (IE) and other systemic bacterial infections is increasing, and people who inject drugs (PWID) have higher rates of discharge against medical advice (AMA) for these infections than patients whose infections are not injection-related. In this study, we characterize factors that contribute to AMA hospital discharge among PWID. Methods: We conducted qualitative interviews with twenty PWID hospitalized with serious injection-related bacterial infections in West Virginia. Participants completed a brief survey and in-depth qualitative interview. Interviews were recorded and transcribed verbatim and analyzed using a codebook developed based on deductive and inductive thematic analysis. We also conducted medical records abstraction and used descriptive statistics to summarize medical and survey data. Results: Average age was 34 years, 55% were female, 95% identified as white, and 75% had a primary diagnosis of IE. Drugs injected prior to hospitalization were methamphetamine (60%), prescription opioids (38%), and/or heroin/fentanyl (25%). Participants cited multiple contributors to AMA discharge including negative interactions with hospital staff that they perceived as stigmatizing, including being searched or monitored for illicit drug use; inadequate management of pain and withdrawal; boredom and confinement during lengthy hospitalizations; and isolation from family and other social supports. Conclusion: We identified multiple factors contributing to AMA discharge that are amenable to intervention. Given the significant morbidity, mortality, and financial costs associated with hospitalizing PWID for serious injection-related bacterial infections, hospitals should be highly motivated to develop and test interventions designed to improve outcomes among these patients.

The International journal on drug policy · 34 citationsread the source →

Zhang L, Zhang L, Mersky JP, Gruber AMH, Kim JY. (2023)MEDLINE-indexed journal, not yet read by usTrauma, violence & abuse

Intergenerational Transmission of Parental Adverse Childhood Experiences and Children's Outcomes: A Scoping Review.

Adverse childhood experiences (ACEs) are among the leading environmental causes of morbidity and mortality. Extending research on within-generation effects, more recent scholarship has explored between-generation consequences of ACEs. Despite growing interest in the intergenerational effects of parents' ACEs on children's outcomes, this line of scholarship has yet to be coalesced into a comprehensive review. The current study is a scoping review on the intergenerational transmission of parental ACEs and children's outcomes. Ten databases such as PubMed, APA PsycArticles, and Social Work Abstracts were searched. To be included, empirical studies must have been published in English and analyzed associations between a cumulative measure of at least four parental ACEs and children's outcomes. Sixty-eight studies qualified for the review and, among these, 60 were published in the most recent 5 years (2018-2022). Fifty-one studies had sample sizes smaller than 500, and 55 focused on the effect of maternal ACEs. Nearly all studies demonstrated that parental ACEs could affect children's outcomes directly or indirectly via mechanisms like maternal mental health problems or parenting-related factors. By scoping the extant literature, this review advances the knowledge base regarding the intergenerational impacts of parental childhood trauma and children's outcomes. It also reveals methodological limitations that should be addressed in future research to strengthen causal inferences along with practical implications for interventions that aim to interrupt the intergenerational transmission of trauma.

Trauma, violence & abuse · 66 citationsread the source →

Kandola A, Lewis G, Osborn DPJ, Stubbs B, Hayes JF. (2020)MEDLINE-indexed journal, not yet read by usThe lancet. Psychiatry

Depressive symptoms and objectively measured physical activity and sedentary behaviour throughout adolescence: a prospective cohort study.

Background: Identifying modifiable risk factors is essential to reduce the prevalence adolescent depression. Self-report data suggest that physical activity and sedentary behaviour might be associated with depressive symptoms in adolescents. We examined associations between depressive symptoms and objectively measured physical activity and sedentary behaviour in adolescents. Methods: From a population-based cohort of adolescents whose mothers were invited to participate in the Avon Longitudinal Study of Parents and Children (ALSPAC) study, we included participants with at least one accelerometer recording and a Clinical Interview Schedule-Revised (CIS-R) depression score at age 17·8 years (reported as age 18 years hereafter). Amounts of time spent in sedentary behaviour and physical activity (light or moderate-to-vigorous) were measured with accelerometers at around 12 years, 14 years, and 16 years of age. Total physical activity was also recorded as count per minute (CPM), with raw accelerometer counts averaged over 60 s epochs. Associations between the physical activity and sedentary behaviour variables and depression (CIS-R) scores at age 18 years were analysed with regression and group-based trajectory modelling. Findings: 4257 adolescents from the 14 901 enrolled in the ALSPAC study had a CIS-R depression score at age 18 years. Longitudinal analyses included 2486 participants at age 12 years, 1938 at age 14 years, and 1220 at age 16 years. Total follow-up time was 6 years. Total physical activity decreased between 12 years and 16 years of age, driven by decreasing durations of light activity (mean 325·66 min/day [SD 58·09] at 12 years; 244·94 min/day [55·08] at 16 years) and increasing sedentary behaviour (430·99 min/day [65·80]; 523·02 min/day [65·25]). Higher depression scores at 18 years were associated with a 60 min/day increase in sedentary behaviour at 12 years (incidence rate ratio [IRR] 1·111 [95% CI 1·051-1·176]), 14 years (1·080 [1·012-1·152]), and 16 years of age (1·107 [1·015-1·208]). Depression scores at 18 years were lower for every additional 60 min/day of light activity at 12 years (0·904 [0·850-0·961]), 14 years (0·922 [0·857-0·992]), and 16 years of age (0·889 [0·809-0·974]). Group-based trajectory modelling across 12-16 years of age identified three latent subgroups of sedentary behaviour and activity levels. Depression scores were higher in those with persistently high (IRR 1·282 [95% CI 1·061-1·548]) and persistently average (1·249 [1·078-1·446]) sedentary behaviour compared with those with persistently low sedentary behaviour, and were lower in those with persistently high levels of light activity (0·804 [0·652-0·990]) compared with those with persistently low levels of light activity. Moderate-to-vigorous physical activity (per 15 min/day increase) at age 12 years (0·910 [0·857-0·966]) and total physical activity (per 100 CPM increase) at ages 12 years (0·941 [0·910-0·972]) and 14 years (0·965 [0·932-0·999]), were negatively associated with depressive symptoms. Interpretation: Sedentary behaviour displaces light activity throughout adolescence, and is associated with a greater risk of depressive symptoms at 18 years of age. Increasing light activity and decreasing sedentary behaviour during adolescence could be an important target for public health interventions aimed at reducing the prevalence of depression. Funding: Details of funding are provided in the Acknowledgments.

The lancet. Psychiatry · 211 citationsread the source →

Spittal MJ, Fedyszyn I, Middleton A, Bassilios B, Gunn J, Woodward A, Pirkis J. (2015)MEDLINE-indexed journal, not yet read by usThe Australian and New Zealand journal of psychiatry

Frequent callers to crisis helplines: who are they and why do they call?

Objective: Frequent callers present a challenge for crisis helplines, which strive to achieve optimal outcomes for all callers within finite resources. This study aimed to describe frequent callers to Lifeline (the largest crisis helpline in Australia) and compare them with non-frequent callers, with a view to furthering knowledge about models of service delivery that might meet the needs of frequent callers. Method: Lifeline provided an anonymous dataset on calls made between December 2011 and May 2013. We assumed calls from the same (encrypted) phone number were made by the same person, and aggregated call level data up to the person level. Individuals who made 0.667 calls per day in any period from 1 week to the full 549 days for which we had data (i.e. 4.7 calls in 7 days, 20 calls in 30 days, 40 calls in 60 days, etc.) were regarded as frequent callers. Results: Our analysis dataset included 411,725 calls made by 98,174 individuals, 2594 (2.6%) of whom met our definition of frequent callers. We identified a number of predictors of being a frequent caller, including being male or transgender, and never having been married. The odds increased with age until 55-64 years, and then declined. Suicidality, self-harm, mental health issues, crime, child protection and domestic violence issues all predicted being a frequent caller. Conclusions: Collectively, frequent callers have a significant impact on crisis lines, and solutions need to be found for responding to them that are in everybody's best interests (i.e. the frequent callers themselves, other callers, telephone crisis supporters who staff crisis lines, and those who manage crisis lines). In striking this balance, the complex and multiple needs of frequent callers must be taken into account.

The Australian and New Zealand journal of psychiatry · 40 citationsread the source →

Hutchings HA, Taylor N, Remesh A, Rafferty J. (2023)MEDLINE-indexed journal, not yet read by usEuropean journal of obstetrics, gynecology, and reproductive biology

A study evaluating quality of life and factors affecting it before, during and after menopause.

Objective: To determine if quality of life (QoL) changes before, during and after menopause and whether these changes are linked to symptoms, demographics, and/or lifestyle factors. Methods: We undertook a cross-sectional online survey. We invited women aged between 35 and 60 years to complete the survey which included the Short-Form 36 (SF-36) generic quality of life measure, the menopause specific Utian-Quality of life (UQOL) measure, and questions about health and wellbeing, menopause symptoms and hormonal stage. The data were analysed with one-way ANOVA analysis and multivariate regression modelling. Results: 279 women completed the survey. Most were aged between 51 and 55 years. In the unadjusted analysis there was a tendency for QoL to deteriorate from pre to peri to menopause and then increase slightly post menopause. This was however not significant in multivariate analysis. Multivariate analysis identified that lifestyle factors significantly influenced QoL. Regular exercise resulted in better QoL scores across a number of the UQol and SF-36 sub-scales. Being very overweight and having more menopause symptoms resulted in worse QoL. Conclusions: Although there was a trend towards worse quality of life in the peri and menopause stages this was not significantly different in adjusted multivariate analyses. Those experiencing more symptoms had significantly worse QoL. Lifestyle factors may affect QoL, but the picture is not straightforward. It is promising that there was a trend toward improved QoL in the post-menopausal stage. These findings should inform education material and promote awareness of the menopause and its impact on QoL. (245).

European journal of obstetrics, gynecology, and reproductive biology · 10 citationsread the source →

Assari S. (2018)MEDLINE-indexed journal, not yet read by usJournal of racial and ethnic health disparities

Life Expectancy Gain Due to Employment Status Depends on Race, Gender, Education, and Their Intersections.

Purpose: Despite the well-established health effects of socioeconomic status (SES), SES resources such as employment may differently influence health outcomes across sub-populations. This study used a national sample of US adults to test if the effect of baseline employment (in 1986) on all-cause mortality over a 25-year period depends on race, gender, education level, and their intersections. Methods: Data came from the Americans' Changing Lives (ACL) study, which followed 2025 Whites and 1156 Blacks for 25 years from 1986 to 2011. The focal predictor of interest was baseline employment (1986), operationalized as a dichotomous variable. The main outcome of interest was time to all-cause mortality from 1986 to 2011. Covariates included baseline age, health behaviors (smoking, drinking, and exercise), physical health (obesity, chronic disease, function, and self-rated health), and mental health (depressive symptoms). A series of Cox proportional hazard models were used to test the association between employment and mortality risk in the pooled sample and based on race, gender, education, and their intersections. Results: Baseline employment in 1986 was associated with a lower risk of mortality over a 25-year period, net of covariates. In the pooled sample, baseline employment interacted with race (HR = .69, 95% CI = .49-.96), gender (HR = .73, 95% CI = .53-1.01), and education (HR = .64, 95% CI = .46-.88) on mortality, suggesting diminished protective effects for Blacks, women, and individuals with lower education, compared to Whites, men, and those with higher education. In stratified models, the association was significant for Whites (HR = .71, 95%CI = .59-.90), men (HR = .60, 95%CI = .43-.83), and individuals with high education (HR = .66, 95%CI = .50-.86) but not for Blacks (HR = .77, 95%CI = .56-1.01), women (HR = .88, 95%CI = .69-1.12), and those with low education (HR = .92, 95%CI = .67-1.26). The largest effects of employment on life expectancy were seen for highly educated men (HR = .50, 95%CI = .32-.78), White men (HR = .55, 95%CI = .38-.79), and highly educated Whites (HR = .63, 95%CI = .46-.84). The effects were non-significant for Black men (HR = 1.10, 95%CI = .68-1.78), Whites with low education (HR = 1.01, 95%CI = .67-1.51), and women with low education (HR = 1.06, 95%CI = .71-1.57). Conclusion: In the USA, the health gain associated with employment is conditional on one's race, gender, and education level, along with their intersections. Blacks, women, and individuals with lower education gain less from employment than do Whites, men, and highly educated people. More research is needed to understand how the intersections of race, gender, and education alter health gains associated with socioeconomic resources.

Journal of racial and ethnic health disparities · 131 citationsread the source →