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Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a population-based study.

Background: Globally, there is a paucity of multimorbidity and comorbidity data, especially for minority ethnic groups and younger people. We estimated the frequency of common disease combinations and identified non-random disease associations for all ages in a multiethnic population. Methods: In this population-based study, we examined multimorbidity and comorbidity patterns stratified by ethnicity or race, sex, and age for 308 health conditions using electronic health records from individuals included on the Clinical Practice Research Datalink linked with the Hospital Episode Statistics admitted patient care dataset in England. We included individuals who were older than 1 year and who had been registered for at least 1 year in a participating general practice during the study period (between April 1, 2010, and March 31, 2015). We identified the most common combinations of conditions and comorbidities for index conditions. We defined comorbidity as the accumulation of additional conditions to an index condition over an individual's lifetime. We used network analysis to identify conditions that co-occurred more often than expected by chance. We developed online interactive tools to explore multimorbidity and comorbidity patterns overall and by subgroup based on ethnicity, sex, and age. Findings: We collected data for 3 872 451 eligible patients, of whom 1 955 700 (50·5%) were women and girls, 1 916 751 (49·5%) were men and boys, 2 666 234 (68·9%) were White, 155 435 (4·0%) were south Asian, and 98 815 (2·6%) were Black. We found that a higher proportion of boys aged 1-9 years (132 506 [47·8%] of 277 158) had two or more diagnosed conditions than did girls in the same age group (106 982 [40·3%] of 265 179), but more women and girls were diagnosed with multimorbidity than were boys aged 10 years and older and men (1 361 232 [80·5%] of 1 690 521 vs 1 161 308 [70·8%] of 1 639 593). White individuals (2 097 536 [78·7%] of 2 666 234) were more likely to be diagnosed with two or more conditions than were Black (59 339 [60·1%] of 98 815) or south Asian individuals (93 617 [60·2%] of 155 435). Depression commonly co-occurred with anxiety, migraine, obesity, atopic conditions, deafness, soft-tissue disorders, and gastrointestinal disorders across all subgroups. Heart failure often co-occurred with hypertension, atrial fibrillation, osteoarthritis, stable angina, myocardial infarction, chronic kidney disease, type 2 diabetes, and chronic obstructive pulmonary disease. Spinal fractures were most strongly non-randomly associated with malignancy in Black individuals, but with osteoporosis in White individuals. Hypertension was most strongly associated with kidney disorders in those aged 20-29 years, but with dyslipidaemia, obesity, and type 2 diabetes in individuals aged 40 years and older. Breast cancer was associated with different comorbidities in individuals from different ethnic groups. Asthma was associated with different comorbidities between males and females. Bipolar disorder was associated with different comorbidities in younger age groups compared with older age groups. Interpretation: Our findings and interactive online tools are a resource for: patients and their clinicians, to prevent and detect comorbid conditions; research funders and policy makers, to redesign service provision, training priorities, and guideline development; and biomedical researchers and manufacturers of medicines, to provide leads for research into common or sequential pathways of disease and inform the design of clinical trials. Funding: UK Research and Innovation, Medical Research Council, National Institute for Health and Care Research, Department of Health and Social Care, Wellcome Trust, British Heart Foundation, and The Alan Turing Institute.

The Lancet. Digital health · 118 citationsread the source →

Fatherhood among healthcare workers: perceived work-family conflict and its influential factors during the COVID-19 pandemic: cross-sectional and exploratory longitudinal findings from the VOICE study.

Background: The increased mental distress among healthcare workers (HCW) during the COVID-19 pandemic has been well documented. Frontline research has rarely focused on fathers among HCW. This web-based multi-center study aimed to evaluate work-family conflict (WFC) among HCW fathers during the COVID-19 pandemic. Methods: Work-family conflict was assessed in cross-sectional, partly overlapping subsamples of 2,844 fathers across four time points (T1: n = 1,155; T2: n = 930; T3: n = 343; T4: n = 416) from April 2020 to May 2022, and compared to 6,981 age-matched mothers and 1,194 male colleagues without children. A longitudinal subsample of n = 188 fathers who participated at two or more time points was analyzed separately. The impact of workload, exhaustion, fear, moral concerns, and institutional trust on HCW fathers' WFC was analyzed using exploratory factor analysis, cross-sectional linear modeling, and longitudinal linear mixed-effects modeling. Results: Fathers reported higher WFC at T1-T3, with levels comparable to mothers, except at T2, when fathers exceeded them. WFC increased from T1 to T4. Risk factors included higher workload, exhaustion, moral concerns, and lower institutional trust, with exploratory longitudinal evidence pointing to a growing protective role of institutional trust against WFC over time. Younger age, cohabitation, children in the household, contact with COVID-19 and full-time employment were also linked to higher WFC. More fathers were working full-time than childless male colleagues. Conclusion: Our findings underscore that WFC among HCW fathers is a structural issue that requires targeted workplace adaptations during crises. Addressing fathers' caregiving roles through flexible and culturally sensitive policies will be crucial to mitigate conflict and promote sustainable work-family integration. Future research should examine causal pathways to develop tailored work-life balance models for fathers.

Frontiers in public health · cohort or longitudinalread the source →

Methodological weakness of the death-word-fragment task: Alternative implicit death anxiety measures.

The efficacy of different implicit death anxiety measures was examined. In Study 1 (N = 133), the death-word-fragment task (DWFT), commonly used to test death-thought accessibility in terror management theory (TMT) research, did not differentiate between mortality salience (MS) and control conditions. Instead, death-related word completions were associated with word dimensions other than MS induction. Study 2 (N = 155) tested three implicit measures (lexical-decision task, dot-probe task, ambiguous pictures task), which differentiated between conditions, revealing greater sensitivity than the DWFT. As TMT research widens its scope, investigating measures to capture implicit death concerns is important.

Death studies · 5 citationsread the source →

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

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

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

The Unintentional Procrastination Scale.

Procrastination refers to the delay or postponement of a task or decision and is often conceptualised as a failure of self-regulation. Recent research has suggested that procrastination could be delineated into two domains: intentional and unintentional. In this two-study paper, we aimed to develop a measure of unintentional procrastination (named the Unintentional Procrastination Scale or the 'UPS') and test whether this would be a stronger marker of psychopathology than intentional and general procrastination. In Study 1, a community sample of 139 participants completed a questionnaire that consisted of several items pertaining to unintentional procrastination that had been derived from theory, previous research, and clinical experience. Responses were subjected to a principle components analysis and assessment of internal consistency. In Study 2, a community sample of 155 participants completed the newly developed scale, along with measures of general and intentional procrastination, metacognitions about procrastination, and negative affect. Data from the UPS were subjected to confirmatory factor analysis and revised accordingly. The UPS was then validated using correlation and regression analyses. The six-item UPS possesses construct and divergent validity and good internal consistency. The UPS appears to be a stronger marker of psychopathology than the pre-existing measures of procrastination used in this study. Results from the regression models suggest that both negative affect and metacognitions about procrastination differentiate between general, intentional, and unintentional procrastination. The UPS is brief, has good psychometric properties, and has strong associations with negative affect, suggesting it has value as a research and clinical tool.

Journal of rational-emotive and cognitive-behavior therapy : RET · 8 citationsread the source →

Trends in the Prevalence and Incidence of Attention-Deficit/Hyperactivity Disorder Among Adults and Children of Different Racial and Ethnic Groups.

Importance: An increasing prevalence of adult attention-deficit/hyperactivity disorder (ADHD) diagnosis and treatment has been reported in clinical settings and administrative data in the United States. However, there are limited data on recent trends of adult ADHD diagnosis among racial/ethnic subgroups. Objective: To examine trends, including associated demographic characteristics, psychiatric diagnoses, and negative outcomes, in the prevalence and incidence of adult ADHD diagnosis among 7 racial/ethnic groups during a 10-year period. Design, setting, and participants: This cohort study investigated trends in the diagnosis of ADHD in adults who identified as African American or black, Native American, Pacific Islander, Latino or Hispanic, non-Hispanic white, Asian American, or other using the Kaiser Permanente Northern California health plan medical records. A total of 5 282 877 adult patients and 867 453 children aged 5 to 11 years who received care at Kaiser Permanente Northern California from January 1, 2007, to December 31, 2016, were included. Data analysis was performed from January 2017 through September 2019. Exposures: Period of ADHD diagnosis. Main outcomes and measures: Prevalence and incidence of licensed mental health clinician-diagnosed ADHD in adults and prevalence of licensed mental health clinician-diagnosed ADHD in children aged 5 to 11 years. Results: Of 5 282 877 adult patients (1 155 790 [21.9%] aged 25-34 years; 2 667 562 [50.5%] women; 2 204 493 [41.7%] white individuals), 59 371 (1.12%) received diagnoses of ADHD. Prevalence increased from 0.43% in 2007 to 0.96% in 2016. Among 867 453 children aged 5 to 11 years (424 449 [48.9%] girls; 260 236 [30.0%] white individuals), prevalence increased from 2.96% in 2007 to 3.74% in 2016. During the study period, annual adult ADHD prevalence increased for every race/ethnicity, but white individuals consistently had the highest prevalence rates (white individuals: 0.67%-1.42%; black individuals: 0.22%-0.69%; Native American individuals: 0.56%-1.14%; Pacific Islander individuals: 0.11%-0.39%; Hispanic or Latino individuals: 0.25%-0.65%; Asian American individuals: 0.11%-0.35%; individuals from other races/ethnicities: 0.29%-0.71%). Incidence of ADHD diagnosis per 10 000 person-years increased from 9.43 in 2007 to 13.49 in 2016. Younger age (eg, >65 years vs 18-24 years: odds ratio [OR], 0.094; 95% CI, 0.088-0.101; P < .001), male sex (women: OR, 0.943; 95% CI, 0.928-0.959; P < .001), white race (eg, Asian patients vs white patients: OR, 0.248; 95% CI, 0.240-0.257; P < .001), being divorced (OR, 1.131; 95% CI, 1.093-1.171; P < .001), being employed (eg, retired vs employed persons: OR, 0.278; 95% CI, 0.267-0.290; P < .001), and having a higher median education level (OR, 2.156; 95% CI, 2.062-2.256; P < .001) were positively associated with odds of ADHD diagnosis. Having an eating disorder (OR, 5.192; 95% CI, 4.926-5.473; P < .001), depressive disorder (OR, 4.118; 95% CI, 4.030-4.207; P < .001), bipolar disorder (OR, 4.722; 95% CI, 4.556-4.894; P < .001), or anxiety disorder (OR, 2.438; 95% CI, 2.385-2.491; P < .001) was associated with higher odds of receiving an ADHD diagnosis. Adults with ADHD had significantly higher odds of frequent health care utilization (OR, 1.303; 95% CI, 1.272-1.334; P < .001) and sexually transmitted infections (OR, 1.289; 95% CI 1.251-1.329; P < .001) compared with adults with no ADHD diagnosis. Conclusions and relevance: This study confirmed the reported increases in rates of ADHD diagnosis among adults, showing substantially lower rates of detection among minority racial/ethnic subgroups in the United States. Higher odds of negative outcomes reflect the economic and personal consequences that substantiate the need to improve assessment and treatment of ADHD in adults.

JAMA network open · 154 citationsread the source →

Dehydroepiandrosterone for women in the peri- or postmenopausal phase.

Background: During menopause a decreasing ovarian follicular response generally causes a fluctuation and eventual decrease in estrogen levels. This can lead to the development of various perimenopausal and postmenopausal symptoms (for example hot flushes, night sweats, vaginal dryness). Dehydroepiandrosterone (DHEA) is one of the main precursors of androgens, which in turn are converted to testosterone and estrogens. It is possible that the administration of DHEA may increase estrogen and testosterone levels in peri- and postmenopausal women to alleviate their symptoms and improve general wellbeing and sexual function (for example libido, dyspareunia, satisfaction). Treatment with DHEA is controversial as there is uncertainty about its effectiveness and safety. This review should clearly outline the evidence for DHEA in the treatment of menopausal symptoms and evaluate its effectiveness and safety by combining the results of randomised controlled trials. Objectives: To assess the effectiveness and safety of administering DHEA to women with menopausal symptoms in the peri- or postmenopausal phase. Search methods: The databases that we searched (3 June 2014) with no language restrictions applied were the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS. We also searched conference abstracts and citation lists in the ISI Web of Knowledge. Ongoing trials were searched in the trials registers. Reference lists of retrieved articles were checked. Selection criteria: We included randomised controlled trials comparing any dose and form of DHEA by any route of administration versus any other active intervention, placebo or no treatment for a minimal treatment duration of seven days in peri- and postmenopausal women. Data collection and analysis: Two authors independently extracted data after assessing eligibility for inclusion and quality of studies. Authors were contacted for additional information. Main results: Twenty-eight trials with 1273 menopausal women were included in this review. Data could be extracted from 16 trials to conduct the meta-analysis. The overall quality of the studies was moderate to low with the majority of studies that were included in the meta-analysis having reasonable methodology. Compared to placebo, DHEA did not improve quality of life (standardised mean difference (SMD) 0.16, 95% confidence interval (CI) -0.03 to 0.34, P = 0.10, 8 studies, 287 women (132 from parallel and 155 from crossover trials), I² = 0%, moderate quality evidence; one trial of the nine that reported on this outcome was removed in a sensitivity analysis as it was judged to be at high risk of bias). DHEA was found to be associated with androgenic side effects (mainly acne) (odds ratio (OR) 3.77, 95% CI 1.36 to 10.4, P = 0.01, 5 studies, 376 women, I² = 10%, moderate quality evidence) when compared to placebo. No associations were found with other adverse effects. It was unclear whether DHEA affected menopausal symptoms as the results from the trials were inconsistent and could not easily be pooled to provide an overall effect due to different types of measurement (for example continuous, dichotomous, change and end scores). DHEA was found to improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55, P = 0.01, 5 studies, 261 women (239 women from parallel trials and 22 women from crossover trials), I² = 0%; one trial judged to be at high risk of bias was removed during sensitivity analysis) compared to placebo. There was no difference in the acne associated with DHEA when comparing studies that used oral DHEA (OR 2.16, 95% CI 0.47 to 9.96, P = 0.90, 3 studies, 136 women, I² = 5%, very low quality evidence) to one study that used skin application of DHEA (OR 2.74, 95% CI 0.10 to 74.87, P = 0.90, 1 study, 22 women, very low quality evidence). The effects did not differ for sexual function when studies using oral DHEA (SMD 0.11, 95% CI -0.13 to 0.35, P = 0.36, 5 studies, 340 women, I² = 0) were compared to a study using intravaginal DHEA (SMD 0.42, 95% CI 0.03 to 0.81, 1 study, 218 women). Test for subgroup differences: Chi² = 1.77, df = 1 (P = 0.18), I² = 43.4%. Insufficient data were available to assess quality of life and menopausal symptoms for this comparison. There were insufficient data available to compare the effects of DHEA to hormone therapy (HT) for quality of life, menopausal symptoms, and adverse effects. No large differences in treatment effects were found for sexual function when comparing DHEA to HT (mean difference (MD) 1.26, 95% CI -0.21 to 2.73, P = 0.09, 2 studies, 41 women, I² = 0%). Authors' conclusions: There is no evidence that DHEA improves quality of life but there is some evidence that it is associated with androgenic side effects. There is uncertainty whether DHEA decreases menopausal symptoms, but DHEA may slightly improve sexual function compared with placebo.

The Cochrane database of systematic reviews · meta-analysis · 22 citationsread the source →

Genomics and proteomics of mycobacteriophage patience, an accidental tourist in the Mycobacterium neighborhood.

Unlabelled: Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host. Importance: The mycobacteriophage Patience genome has a notably lower GC content (50.3%) than its Mycobacterium smegmatis host (67.4%) and has markedly different codon usage biases. The viral genome has an abundance of codons that are rare in the host and are decoded by wobble tRNA pairing, although the phage grows well and expression of most of the genes is detected by mass spectrometry. Patience thus has the genomic profile of a virus that evolved primarily in one type of host genetic landscape (moderate-GC bacteria) but has found its way into a distinctly different high-GC environment. Although Patience genes are ill matched to the host expression apparatus, this is of little functional consequence and has not evidently imposed a barrier to migration across the microbial landscape. Interestingly, comparison of expression levels and codon usage profiles reveals evidence of codon selection as the genome evolves and adapts to its new environment.

mBio · 39 citationsread the source →

Offspring psychopathology following preconception, prenatal and postnatal maternal bereavement stress.

Background: Preconception, prenatal and postnatal maternal stress is associated with increased offspring psychopathology, but findings are inconsistent and need replication. We estimated associations between maternal bereavement stress and offspring autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, suicide attempt and completed suicide. Method: Using Swedish registers, we conducted the largest population-based study to date examining associations between stress exposure in 738,144 offspring born 1992-2000 for childhood outcomes and 2,155,221 offspring born 1973-1997 for adult outcomes with follow-up to 2009. Maternal stress was defined as death of a first-degree relative during (a) the 6 months before conception, (b) pregnancy or (c) the first two postnatal years. Cox proportional survival analyses were used to obtain hazard ratios (HRs) in unadjusted and adjusted analyses. Results: Marginal increased risk of bipolar disorder and schizophrenia following preconception bereavement stress was not significant. Third-trimester prenatal stress increased the risk of ASD [adjusted HR (aHR) 1.58, 95% confidence interval (CI) 1.15-2.17] and ADHD (aHR 1.31, 95% CI 1.04-1.66). First postnatal year stress increased the risk of offspring suicide attempt (aHR 1.13, 95% CI 1.02-1.25) and completed suicide (aHR 1.51, 95% CI 1.08-2.11). Bereavement stress during the second postnatal year increased the risk of ASD (aHR 1.30, 95% CI 1.09-1.55). Conclusions: Further research is needed regarding associations between preconception stress and psychopathological outcomes. Prenatal bereavement stress increases the risk of offspring ASD and ADHD. Postnatal bereavement stress moderately increases the risk of offspring suicide attempt, completed suicide and ASD. Smaller previous studies may have overestimated associations between early stress and psychopathological outcomes.

Psychological medicine · 159 citationsread the source →

Rationale and Methodology of the 2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (CAFVMHS): A 16-year Follow-up Survey: Raison D'être Et Méthodologie De L'enquête De Suivi Sur La Santé Mentale Des Membres Des Forces Armées Canadiennes Et Des Anciens Combattants, 2018 (ESSMFACM).

Objective: Knowledge is limited regarding the longitudinal course and predictors of mental health problems, suicide, and physical health outcomes among military and veterans. Statistics Canada, in collaboration with researchers at the University of Manitoba and an international team, conducted the Canadian Armed Forces Members and Veterans Mental Health Follow-Up Survey (CAFVMHS). Herein, we describe the rationale and methods of this important survey. Method: The CAFVMHS is a longitudinal survey design with 2 time points (2002 and 2018). Regular Force military personnel who participated in the first Canadian Community Health Survey Cycle 1.2-Mental Health and Well-Being, Canadian Forces Supplement (CCHS-CFS) in 2002 (N = 5,155) were reinterviewed in 2018 (n = 2,941). The World Mental Health Survey-Composite International Diagnostic Interview was used with the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. Results: The CAFVMHS includes 2,941 respondents (66% veterans; 34% active duty) and includes data on mental disorder diagnoses, physical health conditions, substance use, medication use, general health, mental health services, perceived need for care, social support, moral injury, deployment experiences, stress, physical activity, military-related sexual assault, childhood experiences, and military and sociodemographic information. Conclusions: The CAFVMHS provides a unique opportunity to further understand the health and well-being of military personnel in Canada over time to inform intervention and prevention strategies and improve outcomes. The data are available through the Statistics Canada Research Data Centres across Canada and can be used cross-sectionally or be longitudinally linked to the 2002 CCHS-CFS data.

Canadian journal of psychiatry. Revue canadienne de psychiatrie · 18 citationsread the source →

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

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

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

Effect of Community Health Worker Support on Clinical Outcomes of Low-Income Patients Across Primary Care Facilities: A Randomized Clinical Trial.

Importance: Addressing the social determinants of health has been difficult for health systems to operationalize. Objective: To assess a standardized intervention, Individualized Management for Patient-Centered Targets (IMPaCT), delivered by community health workers (CHWs) across 3 health systems. Design, setting, and participants: This 2-armed, single-blind, multicenter randomized clinical trial recruited patients from 3 primary care facilities in Philadelphia, Pennsylvania, between January 28, 2015, and March 28, 2016. Patients who resided in a high-poverty zip code, were uninsured or publicly insured, and who had a diagnosis for 2 or more chronic diseases were recruited, and patients were randomized to either the CHW intervention or the control arm (goal setting only). Follow-up assessments were conducted at 6 and 9 months after enrollment. Data were analyzed using an intention-to-treat approach from June 2017 to March 2018. Intervention: Participants set a chronic disease management goal with their primary care physician; those randomized to the CHW intervention received 6 months of tailored support. Main outcomes and measures: The primary outcome was change in self-rated physical health. The secondary outcomes were self-rated mental health, chronic disease control, patient activation, patient-reported quality of primary care, and all-cause hospitalization. Results: Of the 592 participants, 370 (62.5%) were female, with a mean (SD) age of 52.6 (11.1) years. Participants in both arms had similar improvements in self-rated physical health (mean [SD], 1.8 [11.2] vs 1.6 [9.9]; P = .89). Patients in the intervention group were more likely to report the highest quality of care (odds ratio [OR], 1.8; 95% CI, 1.4-2.4; risk difference [RD], 0.12; P < .001) and spent fewer total days in the hospital at 6 months (155 days vs 345 days; absolute event rate reduction, 69%) and 9 months (300 days vs 471 days; absolute event rate reduction, 65%). This reduction was driven by a shorter average length of stay (difference, -3.1 days; 95% CI, -6.33 to 0.22; P = .06) and a lower mean number of hospitalizations (difference, -0.3; 95% CI, -0.6 to 0.0; P = .07) among patients who were hospitalized. Patients in the intervention group had a lower odds of repeat hospitalizations (OR, 0.4; 95% CI, 0.2-0.9; RD, -0.24; P = .02), including 30-day readmissions (OR, 0.3; 95% CI, 0.1-0.9; RD, -0.17; P = .04). Conclusions and relevance: A standardized intervention did not improve self-rated health but did improve the patient-perceived quality of care while reducing hospitalizations, suggesting that health systems may use a standardized intervention to address the social determinants of health. Trial registration: ClinicalTrials.gov identifier: NCT02347787.

JAMA internal medicine · randomised controlled trial · 207 citationsread the source →

Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial.

Background: In current international guidelines the recommendation for intra-aortic balloon pump (IABP) use has been downgraded in cardiogenic shock complicating acute myocardial infarction on the basis of registry data. In the largest randomised trial (IABP-SHOCK II), IABP support did not reduce 30 day mortality compared with control. However, previous trials in cardiogenic shock showed a mortality benefit only at extended follow-up. The present analysis therefore reports 6 and 12 month results. Methods: The IABP-SHOCK II trial was a randomised, open-label, multicentre trial. Patients with cardiogenic shock complicating acute myocardial infarction who were undergoing early revascularisation and optimum medical therapy were randomly assigned (1:1) to IABP versus control via a central web-based system. The primary efficacy endpoint was 30 day all-cause mortality, but 6 and 12 month follow-up was done in addition to quality-of-life assessment for all survivors with the Euroqol-5D questionnaire. A masked central committee adjudicated clinical outcomes. Patients and investigators were not masked to treatment allocation. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00491036. Findings: Between June 16, 2009, and March 3, 2012, 600 patients were assigned to IABP (n=301) or control (n=299). Of 595 patients completing 12 month follow-up, 155 (52%) of 299 patients in the IABP group and 152 (51%) of 296 patients in the control group had died (relative risk [RR] 1·01, 95% CI 0·86-1·18, p=0·91). There were no significant differences in reinfarction (RR 2·60, 95% CI 0·95-7·10, p=0·05), recurrent revascularisation (0·91, 0·58-1·41, p=0·77), or stroke (1·50, 0·25-8·84, p=1·00). For survivors, quality-of-life measures including mobility, self-care, usual activities, pain or discomfort, and anxiety or depression did not differ significantly between study groups. Interpretation: In patients undergoing early revascularisation for myocardial infarction complicated by cardiogenic shock, IABP did not reduce 12 month all-cause mortality. Funding: German Research Foundation; German Heart Research Foundation; German Cardiac Society; Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte; University of Leipzig--Heart Centre; Maquet Cardiopulmonary; Teleflex Medical.

Lancet (London, England) · randomised controlled trial · 641 citationsread the source →

Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Despite increasing public health concerns regarding obesity, few safe and effective drug treatments are available. Combination treatment with sustained-release naltrexone and bupropion was developed to produce complementary actions in CNS pathways regulating bodyweight. The Contrave Obesity Research I (COR-I) study assessed the effect of such treatment on bodyweight in overweight and obese participants. Methods: Men and women aged 18-65 years who had a body-mass index (BMI) of 30-45 kg/m(2) and uncomplicated obesity or BMI 27-45 kg/m(2) with dyslipidaemia or hypertension were eligible for enrolment in this randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 34 sites in the USA. Participants were prescribed mild hypocaloric diet and exercise and were randomly assigned in a 1:1:1 ratio to receive sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB32), sustained-release naltrexone 16 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets (also known as NB16), or matching placebo twice a day, given orally for 56 weeks. The trial included a 3-week dose escalation. Randomisation was done by use of a centralised, computer-generated, web-based system and was stratified by study centre. Co-primary efficacy endpoints at 56 weeks were percentage change in bodyweight and proportion of participants who achieved a decrease in bodyweight of 5% or more. The primary analysis included all randomised participants with a baseline weight measurement and a post-baseline weight measurement while on study drug (last observation carried forward). This study is registered with ClinicalTrials.gov, number NCT00532779. Findings: 1742 participants were enrolled and randomised to double-blind treatment (naltrexone 32 mg plus bupropion, n=583; naltrexone 16 mg plus bupropion, n=578; placebo, n=581). 870 (50%) participants completed 56 weeks of treatment (n=296; n=284; n=290, respectively) and 1453 (83%) were included in the primary analysis (n=471; n=471; n=511). Mean change in bodyweight was -1.3% (SE 0.3) in the placebo group, -6.1% (0.3) in the naltrexone 32 mg plus bupropion group (p<0.0001 vs placebo) and -5.0% (0.3) in the naltrexone 16 mg plus bupropion group (p<0.0001 vs placebo). 84 (16%) participants assigned to placebo had a decrease in bodyweight of 5% or more compared with 226 (48%) assigned to naltrexone 32 mg plus bupropion (p<0.0001 vs placebo) and 186 (39%) assigned to naltrexone 16 mg plus bupropion (p<0.0001 vs placebo). The most frequent adverse event in participants assigned to combination treatment was nausea (naltrexone 32 mg plus bupropion, 171 participants [29.8%]; naltrexone 16 mg plus bupropion, 155 [27.2%]; placebo, 30 [5.3%]). Headache, constipation, dizziness, vomiting, and dry mouth were also more frequent in the naltrexone plus bupropion groups than in the placebo group. A transient increase of around 1.5 mm Hg in mean systolic and diastolic blood pressure was followed by a reduction of around 1 mm Hg below baseline in the naltrexone plus bupropion groups. Combination treatment was not associated with increased depression or suicidality events compared with placebo. Interpretation: A sustained-release combination of naltrexone plus bupropion could be a useful therapeutic option for treatment of obesity. Funding: Orexigen Therapeutics.

Lancet (London, England) · randomised controlled trial · 622 citationsread the source →

The Moral Injury and Distress Scale: Psychometric evaluation and initial validation in three high-risk populations.

Objective: The concept of moral injury resonates with impacted populations, but research has been limited by existing measures, which have primarily focused on war veterans and asked about exposure to potentially morally injurious events (PMIEs) rather than PMIE exposure outcomes. Our goal was to develop and examine the psychometric properties of the Moral Injury and Distress Scale (MIDS), a new measure of the possible emotional, cognitive, behavioral, social, and/or spiritual sequelae of PMIE exposure. Method: The MIDS was validated by surveying three groups: military veterans, healthcare workers, and first responders (N = 1,232). Results: Most respondents (75.0%; n = 924) reported PMIE exposure. Analyses yielded 18 items that contributed to a single latent factor representing moral distress with fully or partially invariant configurations, loadings, and intercepts across occupational groups. The MIDS full-scale score demonstrated excellent internal consistency (α = .95) and moderate 2-week stability (r = .68, p < .001, n = 155). For convergent validity, associations between the MIDS and PMIE exposure measures, as well as putative indicators of moral injury (e.g., guilt, shame), were positive and large (r = .59-.69, p < .001), as were correlations with posttraumatic stress, depressive, and insomnia symptoms (r = .51-.67, p < .001). The MIDS was a stronger predictor of functioning than PMIE exposure measures, explaining seven times greater unique variance (9% vs. 1%-1.3%). Conclusions: The MIDS is the first scale to assess moral injury symptoms indexed to a specific PMIE that is validated across several high-risk populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Psychological trauma : theory, research, practice and policy · 26 citationsread the source →

Anxiety, Depression and Post Traumatic Stress Disorder after critical illness: a UK-wide prospective cohort study.

Background: Survivors of intensive care are known to be at increased risk of developing longer-term psychopathology issues. We present a large UK multicentre study assessing the anxiety, depression and post-traumatic stress disorder (PTSD) caseness in the first year following discharge from an intensive care unit (ICU). Methods: Design: prospective multicentre follow-up study of survivors of ICU in the UK. Setting: patients from 26 ICUs in the UK. Inclusion criteria: patients who had received at least 24 h of level 3 ICU care and were 16 years of age or older. Interventions: postal follow up: Hospital Anxiety and Depression Score (HADS) and the Post-Traumatic Stress Disorder (PTSD) Check List-Civilian (PCL-C) at 3 and 12 months following discharge from ICU. Main outcome measure: caseness of anxiety, depression and PTSD, 2-year survival. Results: In total, 21,633 patients admitted to ICU were included in the study. Postal questionnaires were sent to 13,155 survivors; of these 38% (4943/13155) responded and 55% (2731/4943) of respondents passed thresholds for one or more condition at 3 or 12 months following discharge. Caseness prevalence was 46%, 40% and 22% for anxiety, depression and PTSD respectively; 18% (870/4943 patients) met the caseness threshold for all three psychological conditions. Patients with symptoms of depression were 47% more likely to die during the first 2 years after discharge from ICU than those without (HR 1.47, CI 1.19-1.80). Conclusions: Over half of those who respond to postal questionnaire following treatment on ICU in the UK reported significant symptoms of anxiety, depression or PTSD. When symptoms of one psychological disorder are present, there is a 65% chance they will co-occur with symptoms of one of the other two disorders. Depression following critical illness is associated with an increased mortality risk in the first 2 years following discharge from ICU. Trial registration: ISRCTN Registry, ISRCTN69112866 . Registered on 2 May 2006.

Critical care (London, England) · cohort or longitudinal · 340 citationsread the source →

Development and validation of the Body and Appearance Self-Conscious Emotions Scale (BASES).

The purpose of these studies was to develop a psychometrically sound measure of shame, guilt, authentic pride, and hubristic pride for use in body and appearance contexts. In Study 1, 41 potential items were developed and assessed for item quality and comprehension. In Study 2, a panel of experts (N=8; M=11, SD=6.5 years of experience) reviewed the scale and items for evidence of content validity. Participants in Study 3 (n=135 males, n=300 females) completed the BASES and various body image, personality, and emotion scales. A separate sample (n=155; 35.5% male) in Study 3 completed the BASES twice using a two-week time interval. The BASES subscale scores demonstrated evidence for internal consistency, item-total correlations, concurrent, convergent, incremental, and discriminant validity, and 2-week test-retest reliability. The 4-factor solution was a good fit in confirmatory factor analysis, reflecting body-related shame, guilt, authentic and hubristic pride subscales of the BASES. The development and validation of the BASES may help advance body image and self-conscious emotion research by providing a foundation to examine the unique antecedents and outcomes of these specific emotional experiences.

Body image · cohort or longitudinal · 74 citationsread the source →

The familial risk of autism.

Importance: Autism spectrum disorder (ASD) aggregates in families, but the individual risk and to what extent this is caused by genetic factors or shared or nonshared environmental factors remains unresolved. Objective: To provide estimates of familial aggregation and heritability of ASD. Design, setting, and participants: A population-based cohort including 2,049,973 Swedish children born 1982 through 2006. We identified 37,570 twin pairs, 2,642,064 full sibling pairs, 432,281 maternal and 445,531 paternal half sibling pairs, and 5,799,875 cousin pairs. Diagnoses of ASD to December 31, 2009 were ascertained. Main outcomes and measures: The relative recurrence risk (RRR) measures familial aggregation of disease. The RRR is the relative risk of autism in a participant with a sibling or cousin who has the diagnosis (exposed) compared with the risk in a participant with no diagnosed family member (unexposed). We calculated RRR for both ASD and autistic disorder adjusting for age, birth year, sex, parental psychiatric history, and parental age. We estimated how much of the probability of developing ASD can be related to genetic (additive and dominant) and environmental (shared and nonshared) factors. Results: In the sample, 14,516 children were diagnosed with ASD, of whom 5689 had autistic disorder. The RRR and rate per 100,000 person-years for ASD among monozygotic twins was estimated to be 153.0 (95% CI, 56.7-412.8; rate, 6274 for exposed vs 27 for unexposed ); for dizygotic twins, 8.2 (95% CI, 3.7-18.1; rate, 805 for exposed vs 55 for unexposed); for full siblings, 10.3 (95% CI, 9.4-11.3; rate, 829 for exposed vs 49 for unexposed); for maternal half siblings, 3.3 (95% CI, 2.6-4.2; rate, 492 for exposed vs 94 for unexposed); for paternal half siblings, 2.9 (95% CI, 2.2-3.7; rate, 371 for exposed vs 85 for unexposed); and for cousins, 2.0 (95% CI, 1.8-2.2; rate, 155 for exposed vs 49 for unexposed). The RRR pattern was similar for autistic disorder but of slightly higher magnitude. We found support for a disease etiology including only additive genetic and nonshared environmental effects. The ASD heritability was estimated to be 0.50 (95% CI, 0.45-0.56) and the autistic disorder heritability was estimated to 0.54 (95% CI, 0.44-0.64). Conclusions and relevance: Among children born in Sweden, the individual risk of ASD and autistic disorder increased with increasing genetic relatedness. Heritability of ASD and autistic disorder were estimated to be approximately 50%. These findings may inform the counseling of families with affected children.

JAMA · cohort or longitudinal · 702 citationsread the source →

Placebo effects in children: a review.

Of more than 155,000 PubMed citations found with the search term "placebo," only ~9,000 (5.8%) included the terms "children" or "adolescents." When all these papers were screened, only ~2,000 of them investigated the placebo effect per se, and of those, only ~50 (2.5%) discussed the placebo effect in children and adolescents. In this narrative review, we explore four aspects of the placebo response in children and adolescents: (i) the legal and ethical limitations and restrictions for the inclusion of children in clinical trials as well as in experimental (placebo) research that may explain the poor knowledge base; (ii) the question of whether or not the placebo effect is larger in children and adolescents as compared with adults; (iii) whether the mechanisms underlying the placebo effect are similar between children and adults; and (iv) whether mediators and moderators of the placebo effect are comparable between children and adults. We finally discuss some of the consequences from the current placebo research in adults that may affect both experimental and clinical research in children and adolescents.

Pediatric research · review · 117 citationsread the source →

Developmental Coordination Disorder

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

Physical Therapy · review · 472 citationsread the source →

Psychological therapies for people with borderline personality disorder.

Background: Borderline personality disorder (BPD) is a relatively common personality disorder with a major impact on health services as those affected often present in crisis, often self-harming. Objectives: To evaluate the effects of psychological interventions for people with borderline personality disorder. Search strategy: We conducted a systematic search of 26 specialist and general bibliographic databases (December 2002) and searched relevant reference lists for further trials. Selection criteria: All relevant clinical randomised controlled trials involving psychological treatments for people with BPD. The definition of psychological treatments included behavioural, cognitive-behavioural, psychodynamic and psychoanalytic. Data collection and analysis: We independently selected, quality assessed and data extracted studies. For binary outcomes we calculated a standard estimation of the risk ratio (RR), its 95% confidence interval (CI), and where possible the number need to help/harm (NNT/H). For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). Main results: We identified seven studies involving 262 people, and five separate comparisons. Comparing dialectical behaviour therapy (DBT) with treatment as usual studies found no difference for the outcome of still meeting SCID-II criteria for the diagnosis of BPD by six months (n=28, 1 RCT, RR 0.69 CI 0.35 to 1.38) or admission to hospital in previous three months (n=28, 1 RCT, RR 0.77 CI 0.28 to 2.14). Self harm or parasuicide may decrease at 6 to 12 months (n=63, 1 RCT, RR 0.81 CI 0.66 to 0.98, NNT 12 CI 7 to 108). One study detected statistical difference in favour of people receiving DBT compared with those allocated to treatment as usual for average scores of suicidal ideation at 6 months (n=20, MD -15.30 CI -25.46 to -5.14). There was no difference for the outcome of leaving the study early (n=155, 3 RCTs, RR 0.74 CI 0.52 to 1.04). For the outcome of interviewer-assessed alcohol free days, skewed data are reported and tend to favour DBT. When a substance abuse focused DBT was compared with comprehensive validation therapy plus 12-step substance misuse programme no clear differences were found for service outcomes (n=23, 1 RCT, RR imprisoned 1.09 CI 0.64 to 1.87) or leaving the study early (n=23, 1 RCT, RR 7.58 CI 0.44 to 132.08). When dialectical behaviour therapy-oriented treatment is compared with client centred therapy no differences were found for service outcomes (n=24, 1 RCT, RR admitted 0.33 CI 0.08 to 1.33). However, fewer people in the DBT group displayed indicators of parasuicidal behaviour (n=24, RR 0.13 CI 0.02 to 0.85, NNT 2 CI 2 to 11). There were no differences for outcomes of anxiety and depression (n=24, 1 RCT, RR anxiety BAI >/=10 0.60 CI 0.32 to 1.12; RR depression HDRS >/=10 0.43 CI 0.14 to 1.28) but people who received DBT had less general psychiatric severity than those in the control (MD BPRS at 6 months -7.41 CI -13.72 to -1.10). Finally this one relevant study reports skewed data for suicidal ideation with considerably lower scores for people allocated to DBT. When psychoanalytically oriented partial hospitalization was compared with general psychiatric care the former tended to come off best. People who received treatment in a psychoanalytic orientated day hospital were less likely to be admitted into inpatient care when measured at different time points (e.g. n=44, RR admitted to inpatient 24 hour care >18 to 24 months 0.05 CI 0.00 to 0.77, NNT 3 CI 3 to 10) Fewer people in psychoanalytically oriented partial hospitalization needed day hospital intervention in the 18 months after discharge (n=44, 1 RCT, RR 0.04 CI 0.00 to 0.59, NNT 2 CI 2 to 8). More people in the control group took psychotropic medication by the 30 to 36 month follow-up, than those receiving psychoanalytic treatment (n=44, 1 RCT, RR 0.44 CI 0.25 to 0.80, NNT 3 CI 2 to 7). Anxiety and depression scores were generally lower in the psychoanalytically oriented partial hospitalization group (n=44, 1 RCT, RR >/=14 on BDI 0.52 CI 0.34 to 0.80, NNT 3 CI 3 to 6), as are global severity scores. People receiving psychoanalytic care in a day hospital had better social improvement in social adjustment using the SAS-SR at 6 to 12 months compared with people in general psychiatric care (MD -0.70 CI -1.08 to -0.32). Rates of attrition were the same (n=44, 1 RCT, RR leaving the study early 1.00 CI 0.23 to 4.42). Authors' conclusions: This review suggests that some of the problems frequently encountered by people with borderline personality disorder may be amenable to talking/behavioural treatments but all therapies remain experimental and the studies are too few and small to inspire full confidence in their results. These findings require replication in larger 'real-world' studies.

The Cochrane database of systematic reviews · meta-analysis · 52 citationsread the source →

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 →

Posttraumatic stress disorder treatment outcomes for events related to institutional betrayal.

Institutional betrayal can occur when an organization fails to prevent or respond appropriately to traumatic events perpetrated within its ranks. This experience of violated trust can exacerbate posttraumatic stress disorder (PTSD) symptoms and related sequelae. The primary aim of this quality assurance project was to preliminarily assess whether our standard treatment approach and treatment dosing (single-treatment protocol, 12-15 sessions) was sufficient for patients presenting with institutional betrayal. We compared outcomes for individuals presenting for care following institutional betrayal events (n = 57) with outcomes for a control group of randomly selected nonbetrayed patients (n = 57). Individuals who endorsed a history of sexual abuse were excluded to better isolate the impact of institutional betrayal versus interpersonal factors. Betrayed individuals were more likely to leave treatment before the third session, Cramer's V = .206, particularly betrayed men, Cramer's V = .303, and betrayed Black patients, Cramer's V = .155. Betrayed patients who remained in treatment required additional and different treatment protocols to meet their goals (e.g., written exposure therapy plus cognitive processing therapy [CPT] vs. CPT alone; prolonged exposure [PE] plus CPT vs. CPT alone), Cramer's V = .276. Nevertheless, repeated-measures analyses of variance demonstrated a significant decrease in PTSD, ηp 2  = .61, and depressive symptoms, ηp 2  = .52, regardless of betrayal trauma history. Although evidence-based treatments can help many individuals, these findings raise clinically significant concerns and underscore the detrimental effect of institutional betrayal, justifying future research to improve patient retention in treatment for this specific presentation.

Journal of traumatic stress · 2 citationsread the source →

Characterising youth with callous-unemotional traits and concurrent anxiety: evidence for a high-risk clinical group.

Growing evidence supports the existence of two variants of youth with high callous-unemotional (CU) traits who present with markedly different risk profiles and outcomes, with potential implications for risk assessment and treatment formulation. So far, studies have identified variants of CU youth mainly using data-driven cluster approaches based on levels of CU traits and co-occurring anxiety. Yet, the extent to which this knowledge may be translated into clinical practice is unclear. To this end, the present study employed a severity-based, cut-off approach to systematically characterise CU groups across a range of clinically informative domains, including trauma history, psychiatric symptomatology, affective functioning, attachment style and behavioural risk. Analyses were based on multi-rated data from a community sample of high-risk youths (n = 155, M = 18 years). Consistent with previous studies, we found that, whereas variants show comparable levels of antisocial behaviour, those who present with both high CU and high anxiety report more severe childhood maltreatment, psychological distress, ADHD symptomatology and behavioural risk-including substance use, suicidal ideation and unsafe sex. In addition, these youth show greater attachment insecurity and affective dysregulation, as indexed by levels of irritability and alexithymia. Together, findings indicate that (1) trauma history is a key factor that differentiates variants of CU youth high vs. low on anxiety, and (2) differences in individual functioning across variants point to the need for tailored clinical assessment tools and intervention strategies. Importantly, the present findings indicate that variants of CU youth can be meaningfully differentiated using cut-off based approaches that parallel methods used in clinical assessments.

European child & adolescent psychiatry · 40 citationsread the source →

Long-term exposure to ambient air pollution and risk of dementia: Results of the prospective Three-City Study.

Background: Emerging epidemiological evidence suggests a relationship between exposure to air pollution and dementia. However, most of the existing studies relied on health administrative databases for the diagnosis of dementia. In a large French population-based cohort (the 3C Study), we assessed the effects of particulate matter ≤2.5 µm (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) on the risk of dementia diagnosed with reliable tools. Methods: Participants aged ≥65 years were recruited between 1999 and 2001 and followed for 12 years. At baseline and every 2 years, dementia was suspected on the basis of the neuropsychological and neurological examination and confirmed by an independent committee of clinicians. Exposure to NO2, BC and PM2.5 at the participants' residential address was estimated using land use regression models. For each pollutant and year of follow-up, the 10-year moving average of past exposure was estimated. Multilevel spatial random-effects Cox proportional hazards models were used in which exposure was included as a time-varying variable. Analyses were adjusted for individual (age, sex, education, APOE4 genotype, health behaviours) and contextual (neighbourhood deprivation index) confounders. Results: At baseline, the median age of the 7066 participants was 73.4 years, and 62% were women. The median follow-up duration was 10.0 years during which 791 participants developed dementia (n = 541 Alzheimer's disease (AD) and n = 155 vascular/mixed dementia (VaD)). The 10-year moving average of PM2.5 concentrations ranged from 14.6 to 31.3 µg/m3. PM2.5 concentration was positively associated with dementia risk: HR = 1.20, 95% CI (1.08-1.32) for all-cause dementia, 1.20 (1.09-1.32) for AD, and 1.33 (1.05-1.68) for VaD per 5 µg/m3 PM2.5 increase. No association was detected between NO2 or BC exposure and dementia risk. Conclusion: In this large cohort of older adults, long-term PM2.5 exposure was associated with increased dementia incidence. Reducing PM2.5 emissions might lessen the burden of dementia in aging populations.

Environment international · 90 citationsread the source →

Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Background: Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range of randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence on IF and its impact on specific health-related outcomes while evaluating its evidence quality. Methods: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane databases (from inception up to 8 January 2024) to identify related systematic reviews and meta-analyses of RCTs investigating the association between IF and human health outcomes. We recalculated the effect sizes for each meta-analysis as mean difference (MD) or standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed for populations based on three specific status: diabetes, overweight or obesity, and metabolic syndrome. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. This study is registered with PROSPERO (CRD42023382004). Findings: A total of 351 associations from 23 meta-analyses with 34 health outcomes were included in the study. A wide range of outcomes were investigated, including anthropometric measures (n = 155), lipid profiles (n = 83), glycemic profiles (n = 57), circulatory system index (n = 41), appetite (n = 9), and others (n = 6). Twenty-one (91%) meta-analyses with 346 associations were rated as high confidence according to the AMSTAR criteria. The summary effects estimates were significant at p < 0.05 in 103 associations, of which 10 (10%) were supported by high certainty of evidence according to GRADE. Specifically, compared with non-intervention diet in adults with overweight or obesity, IF reduced waist circumference (WC) (MD = -1.02 cm; 95% CI: -1.99 to -0.06; p = 0.038), fat mass (MD = -0.72 kg; 95% CI: -1.32 to -0.12; p = 0.019), fasting insulin (SMD = -0.21; 95% CI: -0.40 to -0.02; p = 0.030), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.20; 95% CI: -0.38 to -0.02; p = 0.027), total cholesterol (TC) (SMD = -0.29; 95% CI: -0.48 to -0.10; p = 0.003), and triacylglycerols (TG) (SMD = -0.23; 95% CI: -0.39 to -0.06; p = 0.007), but increased fat free mass (FFM) (MD = 0.98 kg; 95% CI: 0.18-1.78; p = 0.016). Of note, compared with the non-intervention diet, modified alternate-day fasting (MADF) reduced fat mass (MD = -0.70 kg; 95% CI: -1.38 to -0.02; p = 0.044). In people with overweight or obesity, and type 2 diabetes, IF increases high-density lipoprotein cholesterol (HDL-C) levels compared to continuous energy restriction (CER) (MD = 0.03 mmol/L; 95% CI: 0.01-0.05; p = 0.010). However, IF was less effective at reducing systolic blood pressure (SBP) than a CER diet in adults with overweight or obesity (SMD = 0.21; 95% CI: 0.05-0.36; p = 0.008). Interpretation: Our findings suggest that IF may have beneficial effects on a range of health outcomes for adults with overweight or obesity, compared to CER or non-intervention diet. Specifically, IF may decreased WC, fat mass, LDL-C, TG, TC, fasting insulin, and SBP, while increasing HDL-C and FFM. Notably, it is worth noting that the SBP lowering effect of IF appears to be weaker than that of CER. Funding: This work was supported by the National Key Research and Development Program of China (Q-JW), the Natural Science Foundation of China (Q-JW and T-TG), Outstanding Scientific Fund of Shengjing Hospital of China Medical University (Q-JW), and 345 Talent Project of Shengjing Hospital of China Medical University (T-TG).

EClinicalMedicine · 59 citationsread the source →

Modifiable risk factors, cardiovascular disease, and mortality in 155 722 individuals from 21 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.

Background: Global estimates of the effect of common modifiable risk factors on cardiovascular disease and mortality are largely based on data from separate studies, using different methodologies. The Prospective Urban Rural Epidemiology (PURE) study overcomes these limitations by using similar methods to prospectively measure the effect of modifiable risk factors on cardiovascular disease and mortality across 21 countries (spanning five continents) grouped by different economic levels. Methods: In this multinational, prospective cohort study, we examined associations for 14 potentially modifiable risk factors with mortality and cardiovascular disease in 155 722 participants without a prior history of cardiovascular disease from 21 high-income, middle-income, or low-income countries (HICs, MICs, or LICs). The primary outcomes for this paper were composites of cardiovascular disease events (defined as cardiovascular death, myocardial infarction, stroke, and heart failure) and mortality. We describe the prevalence, hazard ratios (HRs), and population-attributable fractions (PAFs) for cardiovascular disease and mortality associated with a cluster of behavioural factors (ie, tobacco use, alcohol, diet, physical activity, and sodium intake), metabolic factors (ie, lipids, blood pressure, diabetes, obesity), socioeconomic and psychosocial factors (ie, education, symptoms of depression), grip strength, and household and ambient pollution. Associations between risk factors and the outcomes were established using multivariable Cox frailty models and using PAFs for the entire cohort, and also by countries grouped by income level. Associations are presented as HRs and PAFs with 95% CIs. Findings: Between Jan 6, 2005, and Dec 4, 2016, 155 722 participants were enrolled and followed up for measurement of risk factors. 17 249 (11·1%) participants were from HICs, 102 680 (65·9%) were from MICs, and 35 793 (23·0%) from LICs. Approximately 70% of cardiovascular disease cases and deaths in the overall study population were attributed to modifiable risk factors. Metabolic factors were the predominant risk factors for cardiovascular disease (41·2% of the PAF), with hypertension being the largest (22·3% of the PAF). As a cluster, behavioural risk factors contributed most to deaths (26·3% of the PAF), although the single largest risk factor was a low education level (12·5% of the PAF). Ambient air pollution was associated with 13·9% of the PAF for cardiovascular disease, although different statistical methods were used for this analysis. In MICs and LICs, household air pollution, poor diet, low education, and low grip strength had stronger effects on cardiovascular disease or mortality than in HICs. Interpretation: Most cardiovascular disease cases and deaths can be attributed to a small number of common, modifiable risk factors. While some factors have extensive global effects (eg, hypertension and education), others (eg, household air pollution and poor diet) vary by a country's economic level. Health policies should focus on risk factors that have the greatest effects on averting cardiovascular disease and death globally, with additional emphasis on risk factors of greatest importance in specific groups of countries. Funding: Full funding sources are listed at the end of the paper (see Acknowledgments).

Lancet (London, England) · 1417 citationsread the source →

Coping, meaning in life, and quality of life in congestive heart failure patients.

Objective: The present study examined (1) whether particular coping strategies used to deal with congestive heart failure (CHF) are related to meaning in life across time, and (2) whether meaning in life mediates the effect of coping on health-related quality of life. Methods: A sample of 155 CHF patients received questionnaire packets at two time points, 6 months apart. Main outcome measures included Meaning in Life and Mental and Physical Health-Related Quality of Life (HRQOL). Results: Coping (particularly acceptance/positive reinterpretation and religious coping) was not only related to meaning in life, but also to increased meaning over time. Further, meaning in life was related to both mental and physical components of HRQOL. However, coping was minimally related to HRQOL and its effects were not mediated by meaning in life. Conclusions: These results add to accumulating evidence that life meaning is important in the context of living with a chronic, life-threatening illness. Further, coping--especially acceptance and religious coping--is related to increased life meaning over time in the context of life limiting illness.

Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 64 citationsread the source →

Stability of functional impairment in patients with schizotypal, borderline, avoidant, or obsessive-compulsive personality disorder over two years.

Background: A defining feature of personality disorder (PD) is an enduring pattern of inner experience and behavior that is stable over time. Follow-up and follow-along studies have shown considerable diagnostic instability of PDs, however, even over short intervals. What, then, about personality disorder is stable? The purpose of this study was to determine the stability of impairment in psychosocial functioning in patients with four different PDs, in contrast to patients with major depressive disorder (MDD) and no PD, prospectively over a 2-year period. Method: Six hundred treatment-seeking or treated patients were recruited primarily from clinical services in four metropolitan areas of the Northeastern USA. Patients were assigned to one of five diagnostic groups: schizotypal (STPD) (n=81), borderline (BPD) (n=155), avoidant (AVPD) (n=137), or obsessive-compulsive (OCPD) (n=142) personality disorders or MDD and no PD (n=85), based on the results of semi-structured interview assessments and self-report measures. Impairment in psychosocial functioning was measured using the Longitudinal Interval Follow-up Evaluation (LIFE) at baseline and at three follow-up assessments. Results: Significant improvement in psychosocial functioning occurred in only three of seven domains of functioning and was largely the result of improvements in the MDD and no PD group. Patients with BPD or OCPD showed no improvement in functioning overall, but patients with BPD who experienced change in personality psychopathology showed some improvement in functioning. Impairment in social relationships appeared most stable in patients with PDs. Conclusion: Impairment in functioning, especially social functioning, may be an enduring component of personality disorder.

Psychological medicine · 184 citationsread the source →

Posttraumatic stress disorder and risk of dementia among US veterans.

Context: Posttraumatic stress disorder (PTSD) is highly prevalent among US veterans because of combat and may impair cognition. Objective: To determine whether PTSD is associated with the risk of developing dementia among older US veterans receiving treatment in the Department of Veterans Affairs medical centers. Design: A stratified, retrospective cohort study conducted using the Department of Veterans Affairs National Patient Care Database. Setting: Department of Veterans Affairs medical centers in the United States. Participants: A total of 181 093 veterans 55 years or older without dementia from fiscal years 1997 through 2000 (53 155 veterans with and 127 938 veterans without PTSD). Main outcome measures: During the follow-up period between October 1, 2000, and December 31, 2007, 31 107 (17.2%) veterans were ascertained to have newly diagnosed dementia according to International Classification of Diseases, Ninth Revision, Clinical Modification codes. Results: The mean baseline age of the veterans was 68.8 years, and 174 806 (96.5%) were men. Veterans with PTSD had a 7-year cumulative incident dementia rate of 10.6%, whereas those without had a rate of 6.6% (P < .001). With age as the time scale, Cox proportional hazards models indicated that patients with PTSD were more than twice as likely to develop incident dementia compared with those without PTSD (hazard ratio, 2.31; 95% confidence interval, 2.24-2.39). After multivariable adjustment, patients with PTSD were still more likely to develop dementia (hazard ratio, 1.77; 95% confidence interval, 1.70-1.85). Results were similar when we excluded those with a history of head injury, substance abuse, or clinical depression. Conclusions: In a predominantly male veteran cohort, those diagnosed as having PTSD were at a nearly 2-fold-higher risk of developing dementia compared with those without PTSD. Mechanisms linking these important disorders need to be identified with the hope of finding ways to reduce the increased risk of dementia associated with PTSD.

Archives of general psychiatry · 404 citationsread the source →

Factors related with symptom duration until diagnosis and treatment of symptomatic colorectal cancer.

Background: Colorectal cancer (CRC) survival depends mostly on stage at the time of diagnosis. However, symptom duration at diagnosis or treatment have also been considered as predictors of stage and survival. This study was designed to: 1) establish the distinct time-symptom duration intervals; 2) identify factors associated with symptom duration until diagnosis and treatment. Methods: This is a cross-sectional study of all incident cases of symptomatic CRC during 2006-2009 (795 incident cases) in 5 Spanish regions. Data were obtained from patients' interviews and reviews of primary care and hospital clinical records. Measurements: CRC symptoms, symptom perception, trust in the general practitioner (GP), primary care and hospital examinations/visits before diagnosis, type of referral and tumor characteristics at diagnosis. Symptom Diagnosis Interval (SDI) was calculated as time from first CRC symptoms to date of diagnosis. Symptom Treatment Interval (STI) was defined as time from first CRC symptoms until start of treatment. Nonparametric tests were used to compare SDI and STI according to different variables. Results: Symptom to diagnosis interval for CRC was 128 days and symptom treatment interval was 155. No statistically significant differences were observed between colon and rectum cancers. Women experienced longer intervals than men. Symptom presentation such as vomiting or abdominal pain and the presence of obstruction led to shorter diagnostic or treatment intervals. Time elapsed was also shorter in those patients that perceived their first symptom/s as serious, disclosed it to their acquaintances, contacted emergencies services or had trust in their GPs. Primary care and hospital doctor examinations and investigations appeared to be related to time elapsed to diagnosis or treatment. Conclusions: Results show that gender, symptom perception and help-seeking behaviour are the main patient factors related to interval duration. Health service performance also has a very important role in symptom to diagnosis and treatment interval. If time to diagnosis is to be reduced, interventions and guidelines must be developed to ensure appropriate examination and diagnosis during both primary and hospital care.

BMC cancer · 72 citationsread the source →

The Female Athlete Triad

SUMMARY The female athlete triad (Triad) refers to the interrelationships among energy availability, menstrual function, and bone mineral density, which may have clinical manifestations including eating disorders, functional hypothalamic amenorrhea, and osteoporosis. With proper nutrition, these same relationships promote robust health. Athletes are distributed along a spectrum between health and disease, and those at the pathological end may not exhibit all these clinical conditions simultaneously. Energy availability is defined as dietary energy intake minus exercise energy expenditure. Low energy availability appears to be the factor that impairs reproductive and skeletal health in the Triad, and it may be inadvertent, intentional, or psychopathological. Most effects appear to occur below an energy availability of 30 kcal·kg−1 of fat-free mass per day. Restrictive eating behaviors practiced by girls and women in sports or physical activities that emphasize leanness are of special concern. For prevention and early intervention, education of athletes, parents, coaches, trainers, judges, and administrators is a priority. Athletes should be assessed for the Triad at the preparticipation physical and/or annual health screening exam, and whenever an athlete presents with any of the Triad's clinical conditions. Sport administrators should also consider rule changes to discourage unhealthy weight loss practices. A multidisciplinary treatment team should include a physician or other health-care professional, a registered dietitian, and, for athletes with eating disorders, a mental health practitioner. Additional valuable team members may include a certified athletic trainer, an exercise physiologist, and the athlete's coach, parents and other family members. The first aim of treatment for any Triad component is to increase energy availability by increasing energy intake and/or reducing exercise energy expenditure. Nutrition counseling and monitoring are sufficient interventions for many athletes, but eating disorders warrant psychotherapy. Athletes with eating disorders should be required to meet established criteria to continue exercising, and their training and competition may need to be modified. No pharmacological agent adequately restores bone loss or corrects metabolic abnormalities that impair health and performance in athletes with functional hypothalamic amenorrhea. INTRODUCTION Because the benefits of exercise far outweigh the risks, the American College of Sports Medicine (ACSM) encourages all girls and women to participate in physical activities and sports. In 1992, however, an association of disordered eating, amenorrhea, and osteoporosis seen in activities that emphasize a lean physique was recognized as the female athlete triad (Triad) (148,215). This Position Stand replaces the 1997 ACSM Position Stand (155), updates our understanding, and makes new recommendations for screening, diagnosis, prevention, and treatment of the Triad. EVIDENCE CLASSIFICATION This Position Stand presents clinical recommendations for guiding primary care (Table 1). We used criteria proposed by the American Academy of Family Physicians (52) for evaluating the strength of scientific evidence supporting these clinical recommendations. These criteria categorize the strength of scientific evidence as follows: A, consistent and good-quality evidence for clinical outcomes on mortality, morbidity, symptoms, cost, and quality of life; B, inconsistent or limited quality evidence for these same clinical outcomes; and C, evidence on biochemical, histological, physiological and pathophysiological outcomes, which include hormone concentrations, bone mineral density (BMD), and asymptomatic menstrual disorders such as short luteal phase and anovulation; and evidence based on case studies, consensus, usual practice, and opinion. To avoid misunderstanding, this Position Stand differentiates between two subcategories of evidence: C-1, evidence based on biochemical, histological, physiological, and pathophysiological outcomes; and C-2, evidence based on case studies, consensus, usual practice, and opinion. This Position Stand also presents evidence statements about the current state of knowledge (Table 1). Although the clinical recommendation criteria were not developed for evaluating evidence supporting statements about the current state of knowledge (52), we used these same criteria to evaluate this evidence, as well.TABLE 1: Strength of evidence taxonomy.THREE INTERRELATED SPECTRUMS Low energy availability (with or without eating disorders), amenorrhea, and osteoporosis, alone or in combination, pose significant health risks to physically active girls and women. The potentially irreversible consequences of these clinical conditions emphasize the critical need for prevention, early diagnosis, and treatment. Each clinical condition is now understood to comprise the pathological end of a spectrum of interrelated subclinical conditions between health and disease. Figure 1 illustrates the full range of the Triad. A glossary of terms pertaining to the Triad appears in Table 2.FIGURE 1: Female athlete triad. The spectrums of energy availability, menstrual function, and bone mineral density along which female athletes are distributed (narrow arrows). An athlete's condition moves along each spectrum at a different rate, in one direction or the other, according to her diet and exercise habits. Energy availability, defined as dietary energy intake minus exercise energy expenditure, affects bone mineral density both directly via metabolic hormones and indirectly via effects on menstrual function and thereby estrogen (thick arrows).TABLE 2: Glossary of terms pertaining to the female athlete triad. The goal of ACSM is for every girl and woman's physical condition to be coincident with the upper right corner of Figure 1, which represents the healthy athlete who adjusts her dietary energy intake to compensate for exercise energy expenditure. Thick arrows in this triangle indicate that energy availability promotes bone health and development indirectly by preserving eumenorrhea (Table 2) and estrogen production that restrains bone resorption, and directly by stimulating production of hormones that promote bone formation. As a result, BMD is often above average for the athlete's age. The triangle in the lower left corner of Figure 1 represents the unhealthy condition of athletes who exercise for prolonged periods without increasing dietary energy intake, who severely restrict their diet, or who have clinical eating disorders. Thick arrows in this triangle indicate that low energy availability impairs bone health and development indirectly by inducing amenorrhea and removing estrogen's restraint on bone resorption, and directly by suppressing the hormones that promote bone formation. Bone mineral accrual has slowed or reversed for so long that BMD is below average for age, and one or more stress fractures may have occurred. The narrow arrows in Figure 1 indicate the spectrums of intermediate levels of energy availability, menstrual status, and BMD where other athletes' health status may be distributed. Moderately or recurrently reduced energy availability may induce subclinical menstrual disorders and less severely suppress estrogen and metabolic hormones, and sufficient time may not yet have passed for these athletes to fall far behind their age group in BMD. Energy availability, menstrual status, and BMD move along these spectrums in one direction or the other at different rates according to an athlete's diet and exercise habits. Energy availability can change in a day, but an effect on menstrual status may not become evident for a month or more, and an effect on BMD may not be detectable for a year. Energy Availability This Position Stand refers to a spectrum of energy availability energy availability to low energy availability with or without an eating as dietary energy intake minus exercise energy expenditure, energy availability is the of dietary energy for other exercise energy availability is physiological the of energy used for and This to energy and promote but impairs health. weight in athletes that energy can be energy availability is athletes energy availability by increasing exercise energy more energy energy intake more exercise energy expenditure. eating behaviors such as and or diet and athletes also have eating disorders, which are clinical mental disorders often by other is an eating by eating in which the as and is of weight is at below weight for age and is a for appears in and is an eating in which in the weight a of or and or other behaviors such as or exercise who not meet all criteria for or are as an eating not An may meet all criteria that has or all criteria that and less per This Position Stand refers to a spectrum of menstrual function eumenorrhea to amenorrhea 1). this is recognized by menstrual at but luteal and have Because menstrual are amenorrhea is defined as the of menstrual more is amenorrhea. amenorrhea refers to a in the age of Because is the age for primary amenorrhea was reduced to that energy and development have established that often in athletes in but such are one has to the age of to athletic training The that at a age in but at the same and weight as in Bone This Position Stand refers to a spectrum of BMD bone health to osteoporosis 1). is defined as skeletal by bone strength a to an of Bone strength and the of on the density and of bone mineral and on the quality of bone which may one fractures with the same BMD Although BMD is one of bone this Position Stand on BMD screening and of osteoporosis are based on BMD. is not by bone mineral loss in may also be by not BMD and No BMD between those who and not a osteoporosis is in terms of a BMD at which the for is The criteria for and osteoporosis in women are based on that to average BMD. These criteria BMD to fractures in BMD has a and for fractures in women The for each of one in BMD The 1997 ACSM Position Stand on the Triad the criteria for and osteoporosis in female athletes BMD to fractures in and women are is on for BMD for bone skeletal or in be for in these on the of BMD alone For the Triad, this is by the of BMD to fractures in women to the for that the criteria for and osteoporosis not be to women and the that BMD in these be as to to age and and that below be bone density below the range for in women and as bone density for in The also that the not be used and that osteoporosis be in these low BMD is with clinical that an of bone mineral loss and These include eating disorders, and The recommendations have by the American for Bone and the and the American of Athletes in sports have BMD a BMD in an athlete in the of a ACSM the as a of stress and/or other clinical for with a BMD between and To an of ACSM as clinical for with BMD An athlete's BMD her of energy availability and menstrual status as as her and to other and it is to consider both where her BMD is and it is along the BMD The of amenorrhea not osteoporosis but skeletal her BMD in that not bone but mineral to her BMD. low energy availability, with or without disordered eating, can impair health. with eating disorders include low and disorders the and The for is with a increase in rates to the In one of athletes with eating disorders Although of the of of menstrual function and eating is women are to the of and luteal however, may their are in an a of is not Athletes with luteal may also be at for to development or of of seen in athletes include which the of skeletal levels and BMD as the of menstrual and the loss of BMD may not be fractures occur more in physically active women with menstrual and/or low BMD with a for stress two to in athletes also occur in the of and low BMD to a is a for fractures impairs reproductive and skeletal health. and low BMD increase stress In athletes, the of disordered eating, menstrual disorders, low BMD and stress fractures The of low energy availability without disordered eating or eating disorders is of the of disordered eating and eating disorders in athletes have to or and in the and of the athletes two have clinical eating disorders according to the and of to and of the of eating disorders in female athletes in different of sports eating disorders in of female athletes in sports to of the The other that of female athletes in and sports clinical eating disorders to of the A of a of disordered eating behaviors as as A of weight behaviors eating a exercise for the of and or in the and the of and/or were The of amenorrhea, long to with age, training and weight has in to be as as in and in to in of the of amenorrhea to as training to their to of amenorrhea is in female less of age to women The of primary amenorrhea is less in the and more in and menstrual disorders both and luteal or was in of in at one menstrual of Low BMD has with disordered eating in athletes BMD is lower in athletes in athletes A of that for diagnosis, of between and to and of osteoporosis to in female athletes to and in a of female athletes have the of disordered eating, menstrual disorders and low BMD according to criteria one eating disorders The of the Triad in athletes sports was to but the athletes' BMD were to the the athletes and of the clinical eating disorders and BMD with but not all Triad were and a of weight loss The other two BMD to the Triad in of athletes sports The other the Triad in of athletes these defined the Triad more this Position energy availability, subclinical menstrual disorders or the of amenorrhea, or assessed changes in BMD. should include of low energy availability without disordered eating or an eating luteal and and as as low BMD based the these not yet should be eating, eating disorders and amenorrhea occur more in sports that emphasize Athletes at for low energy availability are those who restrict dietary energy intake, who exercise for prolonged who are and who the of appear to to disordered eating behaviors and clinical eating disorders is a and has on the of and low family and Additional for athletes include early of training and and a increase in training more eating in athletic leanness eating behaviors are for eating disorders that of female athletes and of with disordered eating behaviors were with clinical eating disorders of menstrual have with amenorrhea, but not hormone Most have not to be in the of reproductive function in For weight and are often low in athletes, but and athletes a range of weight and the In exercise training has effect on hormone energy intake is to compensate for exercise energy for stress include low menstrual dietary training and bone Low Energy Availability A for the of eating disorders A of and girls and to be the of clinical eating disorders who were at and levels were and more to be with clinical eating disorders and girls in the and of were and more In athletes, per may not to a clinical eating but the in which the athlete is to the and the availability of weight loss counseling is also for low energy availability is to energy intake to energy In dietary but the same energy by exercise not energy are more such as those for athletes low energy availability may occur without clinical eating disorders, disordered eating behaviors or dietary In reducing dietary intake by more has and skeletal In the Triad, menstrual disorders the not of at the has that is the energy availability of women is reduced by more to less 30 kcal·kg−1 which to the energy in in healthy the energy of is at per the energy of are less 30 kcal·kg−1 also have energy less 30 kcal·kg−1 and with subclinical menstrual disorders women may be less to low energy In the to were in energy availability an average of to 30 kcal·kg−1 are to for the of hormone the have in the for metabolic hormones and to the Low energy availability levels of metabolic hormones and and and loss may also lower or more of these is to a metabolic to but and in women have yet to be of low energy availability and it can occur without a eating on about eating risks of an eating or dietary In luteal and have in women by increasing exercise energy alone In female amenorrhea has by increasing exercise energy without reducing dietary energy intake their was by increasing energy intake without the exercise This of amenorrhea is functional hypothalamic amenorrhea. Low BMD The primary of osteoporosis in women is estrogen which bone also to disorders such as and for a of the bone in athletes with functional hypothalamic amenorrhea As is the case with estrogen in athletes with functional hypothalamic amenorrhea is often by which the of bone 1). In a clinical the of bone and the of bone energy availability was reduced below 30 kcal·kg−1 in women energy availability was to suppress and bone was at energy in relationships those of and that bone Low energy availability may also suppress bone via effects on other hormones, including and and on BMD in female athletes is clinical for the and treatment of Triad disorders are in Table for the Triad can be health consequences are not Although athletes are in sports where is to be one or more clinical consequences of the Triad can occur in in any or physical for the Triad an of the relationships among the spectrum each and rates of along each spectrum 1). screening occur at the preparticipation physical and annual health occur athletes are for such as amenorrhea, stress or or An athlete who presents with one component of the Triad should be assessed for the clinical for the and treatment of Triad eating disorders appear to be and should be to for their and treatment in primary care screening for in primary care should be to meet all criteria for or should not the health-care early and intervention, early and with can athletes eating disorders in the of a clinical eating and behaviors are of energy of these behaviors are of their effects on bone are disordered eating behaviors are also of may indicate a to and behaviors or of eating for the Triad should occur at the preparticipation or annual health screening Athletes with one component of the Triad should be assessed for the on energy intake, dietary weight eating and exercise energy should be of weight and menstrual are in athletes with disordered eating or eating disorders. Athletes with disordered eating should be to a mental health for diagnosis, and recommendations for treatment. status and and other with low such as stress should also be Athletes with disordered eating should be to a mental health for and recommendations for treatment. An athlete with a of one or more of the Triad should have a physical The health-care should be for and of an eating and should be is seen as as include and and the athlete is with an eating by a mental health an should be as the is in the of With functional hypothalamic amenorrhea, the physical is but with may be on In the athlete with disordered eating or an eating an should include a a with rate, function and for can be in severely health-care should not be by is for functional hypothalamic amenorrhea, this condition is by other of amenorrhea for amenorrhea a stimulating hormone and to rule and for the seen in a to rule a and a stimulating hormone for disease. is evidence of on physical exam, and may be to evaluate for an of the or or In to the of that can be seen in functional hypothalamic amenorrhea, indicate can be or a can be to estrogen indirectly by for In functional hypothalamic amenorrhea, are low or is and stimulating hormone are in the A athlete may not to a athletes with this as Additional may be based on and physical and for of primary amenorrhea. with a physician in female athletes or a reproductive is are not of the athlete has a To functional hypothalamic amenorrhea, other of amenorrhea be Bone A of disordered eating or eating disorders for a of or more, and/or a of stress fractures or fractures BMD by is in in those with Triad disorders. should be on the same may an to or for the effects of low energy availability on BMD. in BMD among athletes and are seen between sports and skeletal of low BMD or osteoporosis is based on the BMD of the or the or not or and both should be In less of age, and are the BMD may be in athletes with functional hypothalamic amenorrhea, BMD is often BMD should be assessed a stress or low and a of of amenorrhea, disordered eating or an eating The of bone and the of to BMD in athletes with functional hypothalamic amenorrhea our and recommendations for of the Triad. of bone with a of bone and an increase in bone can irreversible in BMD of bone by of energy availability also that of without clinical menstrual disorders may to their for BMD. and treatment of the Triad should a team including a physician or other health-care or a registered dietitian, and for athletes with disordered eating or an eating a with knowledge of disordered eating and eating disorders in sports be to the of those sports. Additional valuable team members may include a certified athletic trainer, an exercise physiologist, and the athlete's coach, parents and other family members. to the treatment of eating disorders in the should be recognized treatment for the Triad disorders should include a physician other health-care a registered dietitian, and, for athletes with disordered eating or an eating a mental health practitioner. administrators and the health-care team should aim to the Triad education should be on energy availability for prevention should also be to bone mineral accrual in and athletes and to bone health and should be on for their age, including and and on the benefits of exercise for bone health Athletes with menstrual disorders and/or low energy availability with or without disordered eating or eating disorders should be about the of bone mineral osteoporosis, and stress other ACSM that and of sports and athletic and in to potentially weight loss of female and are not may be in BMD of per have in weight in and case of athletes In in BMD of per have seen with weight in but not all the first aim of to menstrual and increase BMD is to diet and exercise to increase energy availability by increasing energy intake, reducing energy expenditure, or a according to the athlete's with recommendations. may be by increasing energy availability to more 30 kcal·kg−1 but the association between in BMD and in weight that increasing BMD may more kcal·kg−1 This to energy in healthy women Athletes eating behaviors should be that in weight may be to increase BMD. is to this is athletes should be to a for counseling and to have their energy availability diet, and weight should all be of such as and are for and may be is to of and increase BMD and fractures in female athletes with the Triad disorders. for female athletes in exercise training may also be those for the at energy availability should continue and be training and The treatment goal for athletes with disordered eating or eating disorders is to status, eating unhealthy that the and that for athletes a need for the is based on a between the athlete and the care The the the more the is In to counseling and treatment group and family An athlete in treatment for disordered eating or eating disorders should meet criteria to continue training and The athlete to with all treatment to be by health-care to on treatment training and and on her status to the and of training and competition A may be used to these of and with the health-care team are the athlete not her or her eating and weight not may need to be training and but should The first aim of treatment is to increase energy availability by increasing energy intake and/or reducing energy expenditure. Athletes without disordered eating or eating disorders should be for Athletes eating behaviors should be that in weight may be to increase BMD. for disordered eating and eating disorders counseling and psychotherapy. group and/or family may also be Athletes with disordered eating and eating disorders who not with treatment may need to be training and are often for weight and for and disorders but agent for in this has to BMD in women with functional hypothalamic amenorrhea. women with functional hypothalamic amenorrhea between two pharmacological or not menstrual was hormone and the and reduced the of menstrual No mass but all those Bone mineral density by less per in two of women with functional hypothalamic amenorrhea who were with but not in a In a of for weight effects of of the of for increasing BMD in athletes and other women with functional hypothalamic amenorrhea without eating disorders is also with clinical and and not but changes in weight were often not that the increase in BMD was by an increase in weight and that the effect of weight the effect of has BMD in any of women with be that pharmacological of menstrual with not metabolic that impair bone health and it is to the low BMD in this Bone mineral density should be in women with functional hypothalamic amenorrhea, disordered eating, and/or low BMD. BMD in an athlete of age with functional hypothalamic amenorrhea intake and may be with the of bone are established as to or to to the athlete less of age with functional hypothalamic amenorrhea to about of and of to this in this age for the treatment of osteoporosis should not be used in the athlete with functional hypothalamic amenorrhea for two The first is of their in women of age The is that the may in a woman's bone for many potentially to a a aim of is to in the athlete who to become of with such as and is the athlete should be about the risks and of a low weight an not her dietary more is to any or new of hormone is for increasing BMD in athletes with functional hypothalamic amenorrhea. In this BMD and other should be to pharmacological and is also on other of energy availability and of function are the of treatment for the Triad. In functional hypothalamic amenorrhea, in BMD are more with in weight with should be in an athlete with functional hypothalamic amenorrhea age BMD is with and Low energy availability with or without eating disorders, functional hypothalamic amenorrhea, and osteoporosis, alone or in combination, pose significant health risks to physically active girls and women. and treatment of these clinical conditions should be a of those who with female athletes to that the benefits of This was for the American College of Sports Medicine by the and by and Additional are to and for their with and this Position This Position Stand replaces the 1997 ACSM Position Female Sports

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