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Research Review: Psychological and psychosocial treatments for children and young people with post-traumatic stress disorder: a network meta-analysis.

Background: Post-traumatic stress disorder (PTSD) is a potentially chronic and disabling disorder that affects a significant minority of youth exposed to trauma. Previous studies have concluded that trauma-focused cognitive behavioural therapy (TF-CBT) is an effective treatment for PTSD in youth, but the relative strengths of different psychological therapies are poorly understood. Methods: We undertook a systematic review and network meta-analyses of psychological and psychosocial interventions for children and young people with PTSD. Outcomes included PTSD symptom change scores post-treatment and at 1-4-month follow-up, and remission post-treatment. Results: We included 32 trials of 17 interventions and 2,260 participants. Overall, the evidence was of moderate-to-low quality. No inconsistency was detected between direct and indirect evidence. Individual forms of TF-CBT showed consistently large effects in reducing PTSD symptoms post-treatment compared with waitlist. The order of interventions by descending magnitude of effect versus waitlist was as follows: cognitive therapy for PTSD (SMD -2.94, 95%CrI -3.94 to -1.95), combined somatic/cognitive therapies, child-parent psychotherapy, combined TF-CBT/parent training, meditation, narrative exposure, exposure/prolonged exposure, play therapy, Cohen TF-CBT/cognitive processing therapy (CPT), eye movement desensitisation and reprocessing (EMDR), parent training, group TF-CBT, supportive counselling and family therapy (SMD -0.37, 95%CrI -1.60 to 0.84). Results for parent training, supportive counselling and family therapy were inconclusive. Cohen TF-CBT/CPT, group TF-CBT and supportive counselling had the largest evidence base. Results regarding changes in PTSD symptoms at follow-up and remission post-treatment were uncertain due to limited evidence. Conclusions: Trauma-focused cognitive behavioural therapy, in particular individual forms, appears to be most effective in the management of PTSD in youth. EMDR is effective but to a lesser extent. Supportive counselling does not appear to be effective. Results suggest a large positive effect for emotional freedom technique, child-parent psychotherapy, combined TF-CBT/parent training, and meditation, but further research is needed to confirm these findings as they were based on very limited evidence.

Journal of child psychology and psychiatry, and allied disciplines · systematic review · 104 citationsread the source →

Smoking cessation for people with severe mental illness (SCIMITAR+): a pragmatic randomised controlled trial.

Background: People with severe mental illnesses such as schizophrenia are three times more likely to smoke than the wider population, contributing to widening health inequalities. Smoking remains the largest modifiable risk factor for this health inequality, but people with severe mental illness have not historically engaged with smoking cessation services. We aimed to test the effectiveness of a combined behavioural and pharmacological smoking cessation intervention targeted specifically at people with severe mental illness. Methods: In the smoking cessation intervention for severe mental illness (SCIMITAR+) trial, a pragmatic, randomised controlled study, we recruited heavy smokers with bipolar disorder or schizophrenia from 16 primary care and 21 community-based mental health sites in the UK. Participants were eligible if they were aged 18 years or older, and smoked at least five cigarettes per day. Exclusion criteria included substantial comorbid drug or alcohol problems and people who lacked capacity to consent at the time of recruitment. Using computer-generated random numbers, participants were randomly assigned (1:1) to a bespoke smoking cessation intervention or to usual care. Participants, mental health specialists, and primary care physicians were unmasked to assignment. The bespoke smoking cessation intervention consisted of behavioural support from a mental health smoking cessation practitioner and pharmacological aids for smoking cessation, with adaptations for people with severe mental illness-such as, extended pre-quit sessions, cut down to quit, and home visits. Access to pharmacotherapy was via primary care after discussion with the smoking cessation specialist. Under usual care participants were offered access to local smoking cessation services not specifically designed for people with severe mental illnesses. The primary endpoint was smoking cessation at 12 months ascertained via carbon monoxide measurements below 10 parts per million and self-reported cessation for the past 7 days. Secondary endpoints were biologically verified smoking cessation at 6 months; number of cigarettes smoked per day, Fagerström Test for Nicotine Dependence (FTND) and Motivation to Quit (MTQ) questionnaire; general and mental health functioning determined via the Patient Health Questionnaire-9 (PHQ-9), the Generalised Anxiety Disorder-7 (GAD-7) questionnaire, and 12-Item Short Form Health Survey (SF-12); and body-mass index (BMI). This trial was registerd with the ISRCTN registry, number ISRCTN72955454, and is complete. Findings: Between Oct 7, 2015, and Dec 16, 2016, 526 eligible patients were randomly assigned to the bespoke smoking cessation intervention (n=265) or usual care (n=261). 309 (59%) participants were male, median age was 47·2 years (IQR 36·3-54·5), with high nicotine dependence (mean 24 cigarettes per day [SD 13·2]), and the most common severe mental disorders were schizophrenia or other psychotic illness (n=343 [65%]), bipolar disorder (n=115 [22%]), and schizoaffective disorder (n=66 [13%]). 234 (88%) of intervention participants engaged with the treatment programme and attended 6·4 (SD 3·5) quit smoking sessions, with an average duration of 39 min (SD 17; median 35 min, range 5-120). Verified quit data at 12 months were available for 219 (84%) of 261 usual care and 223 (84%) of 265 intervention participants. The proportion of participants who had quit at 12 months was higher in the intervention group than in the usual care group, but non-significantly (34 [15%] of 223 [13% of those assigned to group] vs 22 [10%] of 219 [8% of those assigned to group], risk difference 5·2%, 95% CI -1·0 to 11·4; odds ratio [OR] 1·6, 95% CI 0·9 to 2·9; p=0·10). The proportion of participants who quit at 6 months was significantly higher in the intervention group than in the usual care group (32 [14%] of 226 vs 14 [6%] of 217; risk difference 7·7%, 95% CI 2·1 to 13·3; OR 2·4, 95% CI 1·2 to 4·6; p=0·010). The incidence rate ratio for number of cigarettes smoked per day at 6 months was 0·90 (95% CI 0·80 to 1·01; p=0·079), and at 12 months was 1·00 (0·89 to 1·13; p=0·95). At both 6 months and 12 months, the intervention group was non-significantly favoured in the FTND (adjusted mean difference 6 months -0·18, 95% CI -0·53 to 0·17, p=0·32; and 12 months -0·01, -0·39 to 0·38, p=0·97) and MTQ questionnaire (adjusted mean difference 0·58, -0·01 to 1·17, p=0·056; and 12 months 0·64, 0·04 to 1·24, p=0·038). The PHQ-9 showed no difference between the groups (adjusted mean difference at 6 months 0·20, 95% CI -0·85 to 1·24 vs 12 months -0·12, -1·18 to 0·94). For the SF-12 survey, we saw evidence of improvement in physical health in the intervention group at 6 months (adjusted mean difference 1·75, 95% CI 0·21 to 3·28), but this difference was not evident at 12 months (0·59, -1·07 to 2·26); and we saw no difference in mental health between the groups at 6 or 12 months (adjusted mean difference at 6 months -0·73, 95% CI -2·82 to 1·36, and 12 months -0·41, -2·35 to 1·53). The GAD-7 questionnaire showed no difference between the groups (adjusted mean difference at 6 months -0·32 95% CI -1·26 to 0·62 vs 12 months -0·10, -1·05 to 0·86). No difference in BMI was seen between the groups (adjusted mean difference 6 months 0·16, 95% CI -0·54 to 0·85; 12 months 0·25, -0·62 to 1·13). Interpretation: This bespoke intervention is a candidate model of smoking cessation for clinicians and policy makers to address high prevalence of smoking. The incidence of quitting at 6 months shows that smoking cessation can be achieved, but the waning of this effect by 12 months means more effort is needed for sustained quitting. Funding: National Institute for Health Research Health Technology Assessment Programme.

The lancet. Psychiatry · randomised controlled trial · 134 citationsread the source →

Efficacy of Pennebaker's expressive writing intervention in reducing psychiatric symptoms among patients with first-time cancer diagnosis: a randomized clinical trial.

Purpose: The aim of this randomized clinical trial was to examine the efficacy of Pennebaker's expressive writing intervention (EWI) in improving the perceived quality of life (QoL) and in reducing psychiatric symptoms among patients who received a cancer diagnosis. Methods: Seventy-one consecutively recruited patients who received a cancer diagnosis for the first time in their life were randomized into two groups: an EWI group (EWG: n = 35) and a control group (CG n = 36). At the baseline, anamnestic information was collected for all patients, and the patients completed a series of self-reported measures assessing psychiatric symptoms, alexithymia, and health-related QoL. A modified Pennebaker's EWI adapted to cancer diagnosis was also administered to the EWG. Six months later, 32 patients (EWG: n = 17, CG: n = 15) participated in the follow-up and filled out the same questionnaires. Results: The Pennebaker's EWI was effective in decreasing global psychopathology (d =  -.55). Small but significant effects were also observed for alexithymia levels and health-related QoL, with the EWG showing a reduction in alexithymia levels (d =  -.31) and an increase in the mental component of QoL (d = .31) compared to the CG. Conclusions: Our findings indicate that the Pennebaker's EWI is effective in reducing the negative impact of cancer diagnosis on patients' mental health.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · randomised controlled trial · 17 citationsread the source →

Therapist adherence/competence and treatment outcome: A meta-analytic review.

Objective: The authors conducted a meta-analytic review of adherence-outcome and competence-outcome findings, and examined plausible moderators of these relations. Method: A computerized search of the PsycINFO database was conducted. In addition, the reference sections of all obtained studies were examined for any additional relevant articles or review chapters. The literature search identified 36 studies that met the inclusion criteria. Results: R-type effect size estimates were derived from 32 adherence-outcome and 17 competence-outcome findings. Neither the mean weighted adherence-outcome (r = .02) nor competence-outcome (r = .07) effect size estimates were found to be significantly different from zero. Significant heterogeneity was observed across both the adherence-outcome and competence-outcome effect size estimates, suggesting that the individual studies were not all drawn from the same population. Moderator analyses revealed that larger competence-outcome effect size estimates were associated with studies that either targeted depression or did not control for the influence of the therapeutic alliance. Conclusions: One explanation for these results is that, among the treatment modalities represented in this review, therapist adherence and competence play little role in determining symptom change. However, given the significant heterogeneity observed across findings, mean effect sizes must be interpreted with caution. Factors that may account for the nonsignificant adherence-outcome and competence-outcome findings reported within many of the studies reviewed are addressed. Finally, the implication of these results and directions for future process research are discussed.

Journal of consulting and clinical psychology · meta-analysis · 323 citationsread the source →

Decline in the mental health of nurses across the globe during COVID-19: A systematic review and meta-analysis.

Background: Nurses represent the major proportion of frontline health care professionals delivering 24/7 services to patients with an increased vulnerability towards COVID-19 infection. Mental health issues among nurses during the COVID-19 pandemic are poorly reported across the globe. Henceforth, a systematic review and meta-analysis was performed to explore the prevalence and determinants of mental health outcomes (anxiety, stress, depression, PTSD, insomnia) among nurses across the globe due to the COVID-19. Methods: A PRISMA compliant systematic review (PROSPERO-CRD 42020204120) was carried out to identify articles from multiple databases reporting the prevalence of mental health outcomes among nurses. Proportion random effect analysis, I2 statistic, quality assessment, and sensitivity analysis were carried out. Results: Pooled data on mental health outcomes were generated from 25 cross-sectional studies: 32% anxiety (95% confidence interval (CI) = 21%-44%, n (number of studies) = 21, N (sample size) = 13 641), 40.6% stress (95% CI = 25.4%-56.8%, n = 10, N = 4204), 32% depression (95% CI = 21%-44%, n = 17, N = 12 294), 18.6% PTSD (95% CI = 4.8%-38%, n = 3, N = 638), 38.3% insomnia (95% CI = 5.8%-78.6%, n = 2, N = 261) and significant risk factors for mental ailments includes; caring for COVID-19 patients, being a female, low self-efficacy, resilience, social support and having physical symptoms (sore-throat, breathlessness, cough, lethargy, myalgia, fever). Conclusion: The study results highlighted a higher proportion of poor mental health outcomes namely, anxiety, stress, depression, PTSD and insomnia among nurses from different parts of the world. Poor mental health outcomes among nurses warrants the need to implement proactive psychological interventions to deter the collapse of health care systems in responding to the pandemic and in particular all possible efforts should be undertaken to mitigate the risk factors. Health care organizations should provide support to nurses with sufficient flexibility. The disaster preparedness plan envisaged by nations should have provisions to address the mental health of nurses. Greater investment in addressing the global shortage of nurses should be given priority in national health policies. Attractive salary packages should be offered to nurses to prevent their emigration from low- and middle-income countries (LMICs). Registration: PROSPERO (CRD42020204120).

Journal of global health · meta-analysis · 151 citationsread the source →

Maternal history of childhood maltreatment and later parenting behavior: A meta-analysis.

Exposure to maltreatment during childhood (CM) can have deleterious effects throughout the life span of an individual. A parent's history of child maltreatment can also impact his or her own parenting behavior. Theoretically, parents who experienced maltreatment as children may have fewer resources to cope with the challenges of childrearing and may adopt more problematic parenting behaviors. However, empirical studies examining the association between CM and later parenting behavior have yielded mixed results. The aim of this study is to conduct a meta-analysis of studies that have examined the association between exposure to CM and the subsequent parenting outcomes of mothers of 0- to 6-year-old children. A secondary aim is to examine the potential impact of both conceptual and methodological moderators. A total of 32 studies (27 samples, 41 effect sizes, 17,932 participants) were retained for analysis. Results revealed that there is a small but statistically significant association between maternal exposure to CM and parenting behavior (r = -.13, p < .05). Moderator analyses revealed that effect sizes were larger when parenting measures involved relationship-based or negative, potentially abusive behaviors, when samples had a greater number of boys compared to girls, and when studies were older versus more recent. Results are discussed as they relate to the intergenerational transmission of maltreatment and abuse.

Development and psychopathology · meta-analysis · 106 citationsread the source →

Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY): a randomized, controlled trial.

Background and purpose: Decompressive surgery (hemicraniectomy) for life-threatening massive cerebral infarction represents a controversial issue in neurocritical care medicine. We report here the 30-day mortality and 6- and 12-month functional outcomes from the DESTINY trial. Methods: DESTINY (ISRCTN01258591) is a prospective, multicenter, randomized, controlled, clinical trial based on a sequential design that used mortality after 30 days as the first end point. When this end point was reached, patient enrollment was interrupted as per protocol until recalculation of the projected sample size was performed on the basis of the 6-month outcome (primary end point=modified Rankin Scale score, dichotomized to 0 to 3 versus 4 to 6). All analyses were based on intention to treat. Results: A statistically significant reduction in mortality was reached after 32 patients had been included: 15 of 17 (88%) patients randomized to hemicraniectomy versus 7 of 15 (47%) patients randomized to conservative therapy survived after 30 days (P=0.02). After 6 and 12 months, 47% of patients in the surgical arm versus 27% of patients in the conservative treatment arm had a modified Rankin Scale score of 0 to 3 (P=0.23). Conclusions: DESTINY showed that hemicraniectomy reduces mortality in large hemispheric stroke. With 32 patients included, the primary end point failed to demonstrate statistical superiority of hemicraniectomy, and the projected sample size was calculated to 188 patients. Despite this failure to meet the primary end point, the steering committee decided to terminate the trial in light of the results of the joint analysis of the 3 European hemicraniectomy trials.

Stroke · randomised controlled trial · 552 citationsread the source →

Explaining adults' mental health help-seeking through the lens of the theory of planned behavior: a scoping review.

Background: Despite evidence-based efficacy, mental health services are underutilized due to low rates of help-seeking, leaving unmet mental health needs a global concern. The Theory of Planned Behavior (TPB) has been applied to understand the help-seeking process and in the development of behavior change interventions. The aim of this scoping review was to map the literature on the TPB as applied to mental health help-seeking in adults aged >18 years. Methods: This scoping review was conducted based on the methodology presented by Arksey and O'Malley (2005). Six databases (CINAHL, PsycINFO, MEDLINE, ProQuest Health and Medicine, ProQuest Dissertations and Theses, Web of Science) and two grey literature sources (OpenGrey, Google Scholar) were systematically searched in February 2018 and updated in March 2020. Studies that explicitly discussed the TPB in the context of mental health help-seeking were initially selected; only studies that explored formal help-seeking for mental health problems and were published in English were retained. Data were extracted using Microsoft Excel. Results: Initially, 8898 records were identified. Of these, 49 met the selection criteria and were included: 32 were journal articles and 17 were theses. Forty-three papers reported on non-intervention studies and seven articles reported on TPB-based interventions. Most studies (n = 39) identified predictors of help-seeking intentions. Attitudes and perceived behavioral control were significant predictors of intentions in 35 and 34 studies, respectively. Subjective norms were a significant predictor of intentions in 23 studies. Few studies aimed to predict help-seeking behavior (n = 8). Intentions and perceived behavioral control were significant predictors of behavior in seven and six studies, respectively. Only six TPB-based interventions were identified, all used digital technology to influence help-seeking, with mixed results. Conclusions: The present scoping review identified a considerable evidence base on the TPB for predicting mental health help-seeking intentions. Attitudes and perceived behavioral control were frequently found to be significant predictors of help-seeking intentions. Knowledge on the TPB for predicting mental health help-seeking behavior, and on TPB-based interventions, is limited. Thus, the role of the TPB in developing help-seeking interventions remains unclear. Recommendations are presented to address such research gaps and inform policy and practice.

Systematic reviews · review · 44 citationsread the source →

Forgiving the self and physical and mental health correlates: a meta-analytic review.

Self-forgiveness has been conceptualized as a coping strategy that may improve health and well-being. To better understand the functions of self-forgiveness, this meta-analysis examines the correlates of self-forgiveness associated with physical and mental health. For physical health, across 18 samples and 5,653 participants, the correlation was .32. For psychological well-being, across 65 samples and 17,939 participants, the correlation was .45. To augment this primary focus on physical and mental health correlates, we estimated the relationships between self-forgiveness and specific mental health constructs and relationship outcomes. Implications for future basic and applied research on self-forgiveness are discussed.

Journal of counseling psychology · meta-analysis · 45 citationsread the source →

Emotional responses and psychological health among young people amid climate change, Fukushima's radioactive water release, and wars in Ukraine and the Middle East, and the mediating roles of media exposure and nature connectedness: a cross-national analysis.

Background: New global crises are emerging, while existing global crises remain unabated. Coping with climate change, the radioactive water released into the Pacific Ocean subsequent to the Fukushima nuclear accident in Japan, and the wars in Ukraine and the Middle East (hereafter referred to as the wars) as individual crises can negatively affect the psychological health of young people, but little is known about the compounded impact of multiple crises. We aimed to examine: (1) the emotional responses of young people towards each individual crisis, (2) how aggregate levels of emotional engagement in global crises might pose different potential trajectories in psychological health, and (3) the protective or exacerbating role of media exposure and nature connectedness as mediators on psychological health outcomes of young people. Methods: We conducted a cross-national online survey among young people (aged 18-29 years) from China, Portugal, South Africa, the USA, and the UK. We adopted stratified purposive sampling and distributed the survey using online platforms (www.wenjuan.com and www.prolific.com). Individuals were eligible for inclusion in our analysis if they were literate in Chinese or English and had no mental disorders diagnosed within the past 12 months. Participants were asked questions on their demographic characteristics and time spent on social media, including proportion of time exposed to media pertaining to global crises of interest, and they completed surveys based on validated scales that measure depression, anxiety, stress, and wellbeing, as well as emotional responses to each global crisis and nature relatedness. We assessed the survey results using descriptive statistics, ANOVA tests, cluster analysis for individual emotional responses, and structural equation modelling for the aggregate measure of emotional engagement towards individual global crises. Findings: Between Oct 20 and Nov 3, 2023, 2579 individuals participated in the survey, of whom 400 participants from each country (200 male and 200 female participants) were included in our analysis (mean age 24·36 years [SD 2·86]). The mean emotional engagement varied between the global crises of interest (on a scale from 0 to 68, where 0 indicates no emotional response and 68 indicates strong emotional responses across 17 different emotions; wars: 32·42 [SD 14·57]; climate change: 28·79 [14·17]; radioactive water: 21·26 [16·08]), and emotional engagement also varied by country; for instance, for respondents from China, mean emotional engagement in radioactive water was relatively high (39·15 [10·72]) compared with the other countries, and for respondents from the USA, engagement with the wars was relatively low (29·45 [15·78]). We found significant variations in the level of emotional engagement between different crises, with distinct emotional profiles observed among individual countries. To assess the role of media exposure and nature connectedness on psychological outcomes, using structural equation modelling, we constructed a multi-country model comprising Portugal, South Africa, the USA, and the UK, and a standalone model for China. These models elucidated associations between emotional engagement and psychological distress and wellbeing, explaining substantial portions of the variance in both. Notably, while greater emotional engagement in the ecological crises (ie, climate change and radioactive water) generally predicted worse psychological health outcomes, we found the direction of effect for war crises to have positive outcomes for mental health in the standalone China model. Additionally, we found that media exposure mediated the negative effect of wars on psychological distress in the multi-country model, and positive psychological wellbeing in the standalone China model. Moreover, nature connectedness emerged as a potent mediator, effectively mitigating the adverse mental health effects of emotional engagement with some crises, such as radioactive water and climate change. Interpretation: Our findings offer valuable insights into the nuanced dynamics of emotional engagement in global crises and its implications for mental health outcomes among young people across diverse global contexts. Further research is needed to understand the contribution of ongoing and new global crises towards a compounded negative future outlook on young people's mental health to identify effective communication and intervention strategies that can mitigate the effect of this global challenge. Funding: Research Grants Council of Hong Kong, China.

The Lancet. Planetary health · 9 citationsread the source →

Heart rate variability

IN FOCUSHeart rate variabilityHarald M. StaussHarald M. StaussDepartment of Exercise Science, University of Iowa, Iowa City, Iowa 52242Published Online:01 Nov 2003https://doi.org/10.1152/ajpregu.00452.2003MoreSectionsPDF (59 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations the rhythm of the heart has not only fascinated cardiologists but also inspired poets and musicians. Indeed, the periodic beat of the heart was used to define the speed of music. In music notation, the traditional Italian term "moderato" originally referred to one beat of the measure per walking pace (76-80 paces/min) or heartbeat (∼72 beats/min). The use of the heartbeat to define the speed of music may imply that the periodicity of the beat of the heart is very constant. However, this is not necessarily the case. In fact, loss of heart rate variability can indicate severe cardiovascular diseases and reliably predict poor outcome of such conditions (18, 22, 27, 47a). This In Focus article reviews sources of heart rate variability, its role as a prognostic marker for cardiovascular diseases, and its application in estimation of cardiac autonomic nervous system activity. All of these topics have been addressed intensely in articles published in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology during the last two years. In healthy subjects, the sinoatrial node located at the posterior wall of the right atrium initiates each beat of the heart. Due to the unstable membrane potential of the myocytes located in this region, action potentials are generated periodically at a fairly constant frequency. This relatively constant frequency generated by the autorhythmicity of the sinoatrial node is modulated by many factors that add variability to the heart rate signal at different frequencies. According to the Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology (47a) these frequencies are classified into 1) ultra-low frequencies (ULF; >5-h cycle length) that include the circadian rhythm (6, 9, 34, 54); 2) very low frequencies (VLF; >25-s cycle length) that are supposed to be affected by temperature regulation (1, 7, 34, 52, 54) and humoral systems (9, 36); 3) low frequencies (LF; >6-s cycle length in humans) that are sensitive to changes in cardiac sympathetic (and presumably parasympathetic) nerve activity (27, 30); and 4) high frequencies (HF; 2.5- to 6.0-s cycle length in humans) that are synchronized to the respiratory rhythm (5) and are primarily modulated by cardiac parasympathetic innervation (38).The most prominent oscillation in the ULF band of the heart rate spectrum is the circadian rhythm. The autonomic nervous system contributes significantly to circadian heart rate variability. Using long-term recordings in conscious rabbits, Barrett et al. (6) demonstrated a strong circadian rhythm in heart rate, mean arterial blood pressure, renal blood flow, and renal sympathetic nerve activity. The importance of this study is that it clearly demonstrates that sympathetic nerve discharges exhibit a strong circadian rhythmicity. The paraventricular nucleus of the hypothalamus (PVN) appears to play a central role in mediating the circadian rhythm of autonomic nervous system activity. First, GABAergic and glutamatergic neurons project from the suprachiasmatic nuclei of the hypothalamus (SCN) to spinal-projecting neurons of the PVN (12). The SCN is the major central oscillator that triggers the day/night cycle. It receives photic input from the retina (47) and drives many neuroendocrine, metabolic, autonomic, and behavioral circadian rhythms (14, 16, 21, 31, 35, 44, 46, 50). In addition, microinjections of the inhibitory neurotransmitter GABA into the PVN of anesthetized rats elicit dose-dependent decreases in renal sympathetic nerve activity, whereas bicuculline (a GABA antagonist) increases renal sympathetic nerve activity (56). Second, from the PVN, neurons project to the nucleus of the solitary tract (that integrates inputs from the baroreceptors), the nucleus ambiguus (origin of preganglionic parasympathetic neurons to the heart), the rostroventrolateral medulla (location of sympathetic premotor neurons), and the intermediolateral cell column of the thoracolumbar spinal cord (location of preganglionic sympathetic neurons). Thus PVN neurons can modulate autonomic nervous system activity by sending inputs to major sites of autonomic nervous system regulation. As an example, a pivotal role of the PVN for sympathoexcitation during parturition was recently demonstrated in sheep. The increase in sympathetic nerve activity that accompanies birth in maternal animals was prevented by stereotactic lesioning of the PVN (43). Taken together, a major component of the circadian heart rate variability is elicited by diurnal fluctuations in autonomic nervous system activity, generated by corresponding fluctuations of neuronal activity within the PVN, which depend on circadian inputs originating from the SCN.It has been suggested that thermoregulation affects VLF heart rate variability (10, 26). Cooling the heart causes bradycardia, a mechanism used in heart surgeries. Conversely, fever is known to increase heart rate. Raising body core temperature from 36.0 to 36.6°C caused an increase in heart rate by almost 40 beats/min in male subjects (1), whereas acutely reducing ambient temperature from thermoneutral conditions (35°C) to 29, 23, and 17°C, reduced heart rate from 400 to 250 beats/min in 8-day-old rats (7). In addition, lowering temperature in the isolated working rat heart from 37 to 31°C reduced heart rate from 332 to 215 beats/min and markedly increased heart rate variability (28), indicating that parts of the temperature effects on heart rate and heart rate variability are independent from the autonomic nervous system. In contrast to the tachycardia that accompanies acute elevations in temperature, chronically raising ambient temperature in adult rodents from a standard housing temperature of 21-23°C to thermoneutral conditions (29-30°C) reduced heart rate by roughly 50 beats/min in rats (34) and by 200-300 beats/min in mice (54). The authors of these articles (34, 54) suggested that standard housing temperatures are associated with cold stress that causes parallel activation of brown adipose tissue, cardiac, and vasomotor sympathetic drives that elicits nonshivering thermogenesis and tonically elevates heart rate and arterial blood pressure. These and other studies indicate that both direct effects of temperature on pacemaker activity of the sinus node (28) and indirect effects mediated via the autonomic nervous system (11, 25, 51, 55) mediate temperature effects on heart rate and heart rate variability. Thus fluctuation in temperature is an important source of heart rate variability that should not be underestimated. In a more recent study, this was taken into account by core body temperature correction of heart rate variability (3).Endocrine factors affecting heart rate variability include thyroxine, reproductive hormones, the renin-angiotensin system, steroids, and others. Chronic subcutaneous infusion of angiotensin II in rats markedly increased blood pressure and heart rate variability, expressed as standard deviation (9). In contrast, chronic corticosterone treatment is likely to reduce baroreflex-mediated heart rate variability, because baroreceptor-heart rate (39) and baroreceptor-renal sympathetic nerve activity reflex sensitivity (41) were blunted in chronically corticosterone-treated rats. Furthermore, an interaction between angiotensin II and glucocorticoids was recently described. Intracerebro-ventricular microinjections of angiotensin II AT1 receptor antagonists caused marked decreases in mean blood pressure and heart rate in rats chronically treated with corticosterone but not in control animals (40). This interaction is likely to take place in the central nervous system, because peripheral angiotensin II AT1 receptor blockade did not alter the effects of betamethasone treatment on blood pressure, heart rate, and baroreceptor-heart rate reflex sensitivity in newborn lambs (42).Adenosine is a substance less known to affect heart rate variability. It is produced locally in the heart (53) and binds to A1-adenosinergic receptors, which are among the earliest expressed G protein-coupled receptors in the heart (36). The A1-adenosinergic agonist N6-cyclopentyladenosine dose dependently reduced heart rate in murine embryos, whereas 1,3-dipropyl-8-cyclopentylxanthine, an A1-adenosinergic antagonist, increased heart rate (36). Adenosine also exerts central nervous system effects in various brain areas (15, 20). Microinjections of adenosine into the nucleus of the solitary tract of awake rats caused dose-dependent changes in heart rate: low doses (0.01 nmol) produced a bradycardic response, whereas high doses (2.5-5.0 nmol) elicited a tachycardic response (15). Thus adenosine may indeed be involved in the regulation of heart rate and modulate heart rate variability via local cardiac and central nervous system effects. It has been proposed that the intrinsic cardiac nervous system plays an active role in regulating cardiac function (4, 37, 45, 57). This nervous system consists of sympathetic and parasympathetic neurons and interconnecting local circuits (37). Neurons in the canine right atrial ganglionated plexus (RAGP) spontaneously generate activity even after chronic cardiac autonomic denervation (45). Right atrial neurons in patients undergoing coronary artery bypass surgery generated spontaneous activity that was unrelated to the cardiac cycle but sensitive to changes in systemic arterial pressure, indicating that these neurons receive pressure-sensitive sensory inputs (4). In addition, it has been suggested that substance P acts as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig, modulates the response to vagal inputs, and triggers action potentials at the site of parasympathetic ganglia independent of acetylcholine (57). Furthermore, the right atrial (RAGP) and the posterior atrial ganglionated plexus (PAGP) appear to have different functions. Ablation of the PAGP reduced vagally mediated bradycardia by 26%, whereas RAGP ablation completely abolished this response. Inhibition of sympathetically mediated tachycardia by vagal stimulation was attenuated by ablation of either plexus (37). Thus parasympathetic efferent neurons are primarily located in the RAGP, whereas prejunctional parasympathetic-sympathetic interactions also involve neurons within the PAGP (37). The spontaneous activity of neurons in the intrinsic cardiac nervous system, even after cardiac denervation (45), suggests an active role of this system in regulating heart rate. However, the impact of the intrinsic cardiac nervous system on heart rate variability remains to be elucidated. The importance of the autonomic nervous system for heart rate variability in humans becomes apparent in patients following cardiac transplantation, in whom heart rate variability is markedly reduced (49). Although reinnervation is possible after months and years, initially transplanted hearts can be considered to be denervated. Thus the reduced heart rate variability in cardiac transplanted patients (49) underlines the importance of an intact autonomic innervation for spontaneously occurring heart rate variability. A major component of the chronotropic effect of the autonomic nervous system is linked to cAMP. Intracellular cAMP increases the inward current of Na+ (funny current, If), which determines the rate of the slow diastolic depolarization that precedes each action potential. The activity of adenylate cyclase and thus intracellular cAMP levels are increased by stimulation of sympathetic β1-adrenergic receptors and decreased (via a Gi protein) by stimulation of parasympathetic muscarinic receptors. Thus cardiac sympathetic innervation increases the rate of the slow diastolic depolarization and accelerates heart rate, while cardiac parasympathetic innervation elicits opposite effects. Interestingly, parasympathetic-mediated changes in heart rate occur much faster than sympathetic-mediated effects on heart rate (27, 30, 47a). As a result, cardiac sympathetic nervous system activity can only affect LF components of heart rate variability, whereas the parasympathetic nervous system can also modulate HF components. A hitherto unsolved question in this context is if the rapid heart rate response to parasympathetic stimulation compared with the slow effect of sympathetic inputs is due to 1) different kinetics of β1-adrenergic vs. muscarinic receptors, 2) different kinetics of adenylate cyclase vs. phosphodiesterase, the enzyme that cleaves cAMP, or 3) fast parasympathetic-mediated opening of KACh channels (via muscarinic receptors and a GK protein). Support for the latter possibility comes from experiments in the rabbit sinoatrial node that demonstrated that activation of KACh channels contributes to the initial slowing of heart rate as a result of vagal stimulation (8).On the basis of the different frequency response characteristics of sympathetic and parasympathetic modulation of heart rate, frequency analysis of heart rate variability is often used as a tool to determine "autonomic balance" or sympathetic and parasympathetic nervous system activity (27, 47a). As an example, the wavelet transform was recently used to determine cardiac autonomic responses to reperfusion in patients with thrombolysis after coronary thrombosis. Depending on the location of the infarct, marked alterations in LF or HF spectral power of heart rate or in the LF/HF ratio was observed in all successful reperfusions (48).The HF component corresponds to the frequency of respiration and is driven by the vagus as indicated by the strong respiratory pattern of cardiac vagal motoneurons in the nucleus ambiguus (38). The LF component has been ascribed to sympathetic modulation of cardiac pacemaker activity, because a variety of studies demonstrated that acute interventions that increase sympathetic nervous system activity, such as orthostatic perturbations (17, 19, 33), mental stress (32), or handgrip exercise (13, 24) increases LF spectral power of heart rate (27, 30). In addition to acute perturbations of cardiac sympathetic nerve activity, feedback oscillations generated by the baroreceptor reflex also appear to contribute to LF spectral power of heart rate as it was demonstrated that sinoaortic denervation markedly reduces the LF component (27, 30). Despite the strong modulation of heart rate by the autonomic nervous system, the LF and HF spectral components of heart rate variability may not always be very reliable markers for cardiac sympathetic and parasympathetic "tone" (30). In a recent study, muscle sympathetic nerve activity was recorded together with heart rate variability during application of lower body negative pressure that is known to increase muscle sympathetic nerve activity (17, 33). At higher levels of lower body negative pressure (-15 mmHg), both muscle sympathetic nerve activity and relative LF spectral power of heart rate increased significantly, whereas HF spectral power decreased (17). These findings suggest that LF spectral power reflects cardiac sympathetic "tone." However, no correlation within subjects was found between changes in LF/HF ratio and muscle sympathetic nerve activity (17). Thus heart rate variability does not reliably reflect the sympathetic response to orthostatic stress. Respiration-related fluctuation of heart rate (respiratory sinus arrhythmia) is probably the most often investigated component of heart rate variability, as it is believed that this component reflects respiration-driven vagal modulation of sinus arrhythmia (27). In a recent study, Rentero et al. (38) recorded the electrical activity from cardiac vagal motoneurons in the nucleus ambiguus. Firing of these neurons was modulated by the central respiratory cycle. This and other studies support the view that respiratory sinus arrhythmia is generated by central coupling of the respiratory oscillator with autonomic centers in the brain stem. However, a mechanical cardiopulmonary coupling as a source of respiration-related heart rate variability has also been suggested (5). The Bainbridge reflex causes a tachycardia in response to hypervolemia. This reflex is initiated by atrial mechanoreceptors and uses efferent sympathetic and parasympathetic pathways to modulate heart rate in response to changes in central venous pressure (23). Thus respiratory changes in central blood volume cause corresponding respiratory fluctuations in cardiac autonomic nervous system activity via the Bainbridge reflex. Only the parasympathetic component of the efferent pathway of the reflex can contribute to respiratory sinus arrhythmia, because sympathetic actions on heart rate are too damped to follow the respiratory frequency. The gain and phase of the transfer function between respiratory changes in lung volume and R-R intervals of the ECG were calculated in human subjects during graded changes in central blood volume (5). At the respiratory frequency, the phase was -180 degree, indicating that an inspiratory increase in central blood volume was associated with a decrease in R-R interval (increase in heart rate). Furthermore, the gain of the transfer function at the respiratory frequency steadily increased with increasing central volumes (except at the highest volume). Both of these findings confirm the presence of the Bainbridge reflex in humans (5). Thus, in addition to the central coupling of respiratory oscillators with cardiovascular centers, the Bainbridge reflex may contribute to respiration-related heart rate variability by mechanical cardiopulmonary coupling. There is general agreement that low heart rate variability is an unfavorable prognostic marker for cardiovascular diseases, such as diabetic autonomic neuropathy, hypertension, myocardial infarction, and heart failure (18, 22, 27, 29, 47a). Heart rate variability (variance of R-R intervals) was reduced in patients with mild hypertension (29) compared with normal values (1,134 ± 202 vs. 3,466 ± 1,018 ms2) provided by the Task Force (47a). In the rat model of myocardial infarction-induced congestive heart failure, Francis and colleagues (18) reported loss of spontaneous heart rate variability 6 wk after coronary artery ligation. Interestingly, reduced heart rate variability was also observed in a rat model of depression that is based on chronic (4 wk) mild stress application (22). Because depression is an independent risk factor for coronary artery disease, this finding may realistically model a human disease process. The reduction in heart rate variability was abolished by β-adrenergic receptor blockade, indicating that the reduced heart rate variability in this model of depression is related to elevated cardiac sympathetic tone (22).In summary, heart rate variability is generated by multiple factors not exclusively limited to the autonomic nervous system. Specific frequency components of heart rate variability mirror acute perturbations of the autonomic nervous system but do not always reflect autonomic nervous system activity. Simple statistics of heart rate variability, such as the standard deviation of R-R intervals in the ECG, can reliably predict the prognosis of cardiovascular diseases.I thank Dr. R. McAllen for critically reviewing the manuscript. References 1 Aoki K, Stephens DP, and Johnson JM. Diurnal variation in cutaneous vasodilator and vasoconstrictor systems during heat stress. 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American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · review · 309 citationsread the source →

The global burden of perinatal common mental health disorders and substance use among migrant women: a systematic review and meta-analysis.

Background: There are one billion migrants globally, of whom 82 million are forced migrants. Pregnant migrants face pre-migration stressors such as conflict, transit stressors including poverty, and post-migration stressors including navigating the immigration system; these stressors can make them vulnerable to mental illness. We aimed to assess the global prevalence of and risk factors for perinatal mental health disorders or substance use among women who are migrants. Methods: In this systematic review and meta-analysis, we searched OVID MEDLINE, Embase, PsycINFO, CENTRAL, Global Health, Scopus, and Web of Science for studies published from database inception until July 8, 2022. Cohort, cross-sectional, and interventional studies with prevalence data for any mental illness in pregnancy or the postnatal period (ie, up to a year after delivery) or substance use in pregnancy were included. The primary outcome was the prevalence of perinatal common mental health disorders among women who are migrants, globally. Data for study quality and risk factors were also extracted. A random-effects meta-analysis was used to calculate pooled prevalence estimates, when appropriate. Sensitivity analyses were conducted according to study quality, sample representativeness, and method of outcome assessment. Risk factor data were synthesised narratively. This study is registered with PROSPERO, CRD42021226291. Findings: 18 650 studies were retrieved, of which 135 studies comprising data from 621 995 participants met the inclusion criteria. 123 (91%) of 135 studies were conducted in high-income host countries. Five (4%) of 135 studies were interventional, 40 (30%) were cohort, and 90 (66%) were cross-sectional. The most common regions of origin of participants were South America, the Middle East, and north Africa. Only 26 studies presented disaggregated data for forced migrants or economic migrants. The pooled prevalence of perinatal depressive disorders was 24·2% (range 0·5-95·5%; I2 98·8%; τ2 0·01) among all women who are migrants, 32·5% (1·5-81·6; 98·7%; 0·01) among forced migrants, and 13·7% (4·7-35·1; 91·5%; 0·01) among economic migrants (p<0·001). The pooled prevalence of perinatal anxiety disorders was 19·6% (range 1·2-53·1; I2 96·8%; τ2 0·01) among all migrants. The pooled prevalence of perinatal post-traumatic stress disorder (PTSD) among all migrant women was 8·9% (range 3·2-33·3; I2 97·4%; τ2 0·18). The pooled prevalence of perinatal PTSD among forced migrants was 17·1% (range 6·5-44·3; I2 96·6%; τ2 0·32). Key risk factors for perinatal depression were being a recently arrived immigrant (ie, approximately within the past year), having poor social support, and having a poor relationship with one's partner. Interpretation: One in four women who are migrants and who are pregnant or post partum experience perinatal depression, one in five perinatal anxiety, and one in 11 perinatal PTSD. The burden of perinatal mental illness appears higher among women who are forced migrants compared with women who are economic migrants. To our knowledge, we have provided the first pooled estimate of perinatal depression and PTSD among women who are forced migrants. Interpreting the prevalence estimate should be observed with caution due to the very wide range found within the included studies. Additionally, 66% of studies were cross-sectional representing low quality evidence. These findings highlight the need for community-based routine perinatal mental health screening for migrant communities, and access to interventions that are culturally sensitive, particularly for forced migrants who might experience a higher burden of disease than economic migrants. Funding: UK National Institute for Health Research (NIHR); March of Dimes European Preterm Birth Research Centre, Imperial College; Imperial College NIHR Biomedical Research Centre; and Nuffield Department of Population Health, University of Oxford.

The Lancet. Public health · meta-analysis · 63 citationsread the source →

Influenza vaccine as a coronary intervention for prevention of myocardial infarction.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. Influenza is one of the leading infectious causes of morbidity and mortality globally, and evidence is accumulating that it can precipitate acute myocardial infarction (AMI). This is thought to be due to a range of factors including inflammatory release of cytokines, disruption of atherosclerotic plaques and thrombogenesis, which may acutely occlude a coronary artery. There is a large body of observational and clinical trial evidence that shows that influenza vaccine protects against AMI. Estimates of the efficacy of influenza vaccine in preventing AMI range from 15% to 45%. This is a similar range of efficacy compared with the accepted routine coronary prevention measures such as smoking cessation (32-43%), statins (19-30%) and antihypertensive therapy (17-25%). Influenza vaccine should be considered as an integral part of CVD management and prevention. While it is recommended in many guidelines for patients with CVD, rates of vaccination in risk groups aged <65 years are very low, in the range of 30%. The incorporation of vaccination into routine CVD prevention in patient care requires a clinical practice paradigm change.

Heart (British Cardiac Society) · review · 94 citationsread the source →

Factors associated with mental health outcomes in a Muslim community following the Christchurch terrorist attack.

Background: On 15 March 2019, a white supremacist terrorist attacked two mosques in Christchurch, New Zealand. Fifty-one people were killed and another 40 sustained non-fatal gunshot injuries. Aims: To examine the mental health of the Muslim community, and individual and exposure-related factors associated with mental health outcomes. Method: This is the baseline analysis of a longitudinal study of adults from the Muslim community interviewed 11-32 months after the shootings. It included a diagnostic interview (MINI), measures of sociodemographic factors, prior mental health, prior traumatic events, exposure in the attacks, discrimination, life stressors, social support and religious coping. Logistic regression models examined associations with mental health outcomes. Results: The sample comprised 189 participants (mean age 41 (s.d. = 13); 60% female), and included: bereaved, 17% (n = 32); injured survivors 12% (n = 22); non-injured survivors, 19% (n = 36); family members of survivors, 35% (n = 67); and community members without the above exposures, 39% (n = 74). Overall, 61% had at least one mental disorder since the attacks. Those bereaved (P < 0.01, odds ratio 4.28, 95% CI 1.75-10.49) and survivors, whether injured (P < 0.001, odds ratio 18.08, 95% CI 4.70-69.60) or not (P < 0.01, odds ratio 5.26, 95% CI 1.99-13.89), had greater odds of post-traumatic stress disorder. Those bereaved (P < 0.001, odds ratio 5.79, 95% CI 2.49-13.46) or injured (P = 0.04, odds ratio 4.43, 95% CI 1.07-18.28) had greater odds of depression. Conclusions: Despite unique features of this attack on a Muslim population, findings accord with previous studies. They suggest generalisability of psychopathology after terror attacks, and that being bereaved or directly experiencing such events is associated with adverse mental health outcomes. Trial registration number: The study is registered on the Australian NZ Clinical Trials Registry (ACTRN12620000909921).

BJPsych open · 3 citationsread the source →

Indirect Relations Between Transgressive Acts and General Combat Exposure and Moral Injury.

Introduction: Moral injury describes the deleterious effects of acts of commission (e.g., killing noncombatants), omission (e.g., failing to prevent a massacre), or betrayal (i.e., by a trusted authority figure) during military service that transgress accepted behavioral boundaries and norms. Transgressive acts are proposed to lead to a guilt- and shame-based syndrome consisting of post-traumatic stress disorder (PTSD) symptoms, demoralization, self-handicapping, and self-injury. In this study, we tested a frequently cited model of moral injury and assessed the associations between potentially transgressive acts, moral injury outcomes, and guilt and fear. Additionally, we sought to clarify the relative contribution of transgressive and nontransgressive/general combat exposure to moral injury. On the basis of previous research and theory, we anticipated that the transgressive acts would be related to outcomes through guilt and that nontransgressive combat exposure would be related to outcomes through fear. Materials and methods: Secondary analysis was conducted on data from a sample of combat-exposed male veterans at a Midwestern Veterans Affairs (VA) medical center (N = 190) who participated in a larger parent study on postdeployment readjustment. Structural equation modeling was used to test the pathways from transgressive and nontransgressive combat exposure to PTSD symptoms and suicidality through combat-related guilt and combat-related fear. The institutional review boards of the Midwestern VA medical center and the university of the affiliated researchers approved the study. Results: In total, 38% (n = 72) of the sample reported a potentially transgressive act as one of their three worst traumatic events. The most common potentially transgressive act was killing an enemy combatant (17%; n = 32). In structural equation modeling analyses. potentially transgressive acts were indirectly related to both suicidality (β = 0.09, p < 0.01) and PTSD symptoms (β = 0.06, p < 0.05) through guilt. General combat exposure was indirectly related to PTSD through fear, β = 0.19, p < 0.01. Combat exposure was not directly or indirectly related to suicidality. Conclusion: Overall, these findings suggest that veterans with a history of potentially transgressive acts may present to the VA with a constellation of symptoms that are associated with combat-related guilt. Transgressive acts were identified using a qualitative approach, allowing a broader sampling of this domain. Results were limited by the use of self-report data and by gathering data from participants who were Veterans seeking compensation and pension evaluations for PTSD. The clinical implications suggest that focusing on fear-related outcomes and ignoring guilt- and shame-based reactions may lead to an incomplete case conceptualization. Clinicians working with veterans with moral injury are encouraged to prepare themselves for the discomfiting therapeutic experiences of bearing witness to and empathizing with clients' memories of their actions, which may include atrocities. Effective and empathic treatments that address the guilt and shame associated with transgressive acts are needed to adequately care for returning veterans.

Military medicine · 27 citationsread the source →

Stress Is Associated With Neurocognitive Function in Hispanic/Latino Adults: Results From HCHS/SOL Socio-Cultural Ancillary Study.

Objectives: The purpose of this study was to evaluate the hypothesis that chronic and acculturative stress would be negatively associated with neurocognitive function among middle aged to older Hispanics/Latinos. Method: Our analytic sample consisted of 3,265 participants (mean age = 56.7 (±0.24)) from the Hispanic Community Health Study/Study of Latinos who participated in its Sociocultural Ancillary Study. During the baseline phase of this project, participants were assessed on multiple domains of neurocognitive function, and completed self-report measures of chronic and acculturative stress. Results: Each standard deviation increase in chronic stress was associated with lower performance in a verbal learning task (B = -.17, 95% CI [-.32, -.01]); this association was no longer significant after adjusting for mental and physical health symptoms, including depression and anxiety symptoms, and cardiovascular health. A standard deviation increase in acculturative stress was associated with poorer performance in all cognitive measures (Bs range = -.13 to -1.03). Associations of acculturation stress with psychomotor speed, verbal learning, and word fluency remained significant after adjusting for mental and physical health symptoms. Discussion: Our results suggest that mental and physical health may help explain some cross-sectional associations between stress and cognition and highlight the need to examine culture-specific psychosocial stressors to better understand the context of psychosocial risk factors for neurocognitive performance.

The journals of gerontology. Series B, Psychological sciences and social sciences · 20 citationsread the source →

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

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

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

Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study.

Background: Interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain is increasing, because of their potential to reduce opioid dose requirements. We aimed to investigate cannabis use in people living with chronic non-cancer pain who had been prescribed opioids, including their reasons for use and perceived effectiveness of cannabis; associations between amount of cannabis use and pain, mental health, and opioid use; the effect of cannabis use on pain severity and interference over time; and potential opioid-sparing effects of cannabis. Methods: The Pain and Opioids IN Treatment study is a prospective, national, observational cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited through community pharmacies across Australia, completed baseline interviews, and were followed up with phone interviews or self-complete questionnaires yearly for 4 years. Recruitment took place from August 13, 2012, to April 8, 2014. Participants were asked about lifetime and past year chronic pain conditions, duration of chronic non-cancer pain, pain self-efficacy, whether pain was neuropathic, lifetime and past 12-month cannabis use, number of days cannabis was used in the past month, and current depression and generalised anxiety disorder. We also estimated daily oral morphine equivalent doses of opioids. We used logistic regression to investigate cross-sectional associations with frequency of cannabis use, and lagged mixed-effects models to examine temporal associations between cannabis use and outcomes. Findings: 1514 participants completed the baseline interview and were included in the study from Aug 20, 2012, to April 14, 2014. Cannabis use was common, and by 4-year follow-up, 295 (24%) participants had used cannabis for pain. Interest in using cannabis for pain increased from 364 (33%) participants (at baseline) to 723 (60%) participants (at 4 years). At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01-1·29, for less frequent cannabis use; and 1·17, 1·03-1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09-1·35; and 1·14, 1·03-1·26), lower pain self-efficacy scores (0·97, 0·96-1·00; and 0·98, 0·96-1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03-1·12; and 1·10, 1·06-1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation. Interpretation: Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain. Funding: National Health and Medical Research Council and the Australian Government.

The Lancet. Public health · 166 citationsread the source →

Promoting Colorectal Cancer Screening in South Asian Muslims Living in the USA.

Colorectal cancer is one of the more common forms of cancer in South Asian men and women. Despite the rates of colorectal cancer (CRC) in South Asians, the CRC screening rates remain low in South Asians and Muslims compared with those in Whites and other ethnic minorities in the USA. Religious and cultural barriers have been examined in relation to other types of cancer such as breast and cervical cancers. However, few data are available about CRC screening among Muslims, particularly South Asian American Muslims. A community-based participatory research approach was used to assess attitudes toward CRC screening and various cultural, religious, and gender barriers that prevent CRC screening expressed by Muslim South Asian men and women in the larger San Francisco Bay Area. Six focus groups were conducted (three males and three females) with South Asian American Muslims. The focus groups consisted of a total sample size of n = 32, with 15 men and 17 women, with the average age of participants being 57 years old. This study highlighted key religious, cultural, and gender barriers to CRC screening including lack of awareness of CRC, the notion of fatalism as it relates to screening, lack of emphasis on preventive health, the need to preserve modesty, and stigma around certain CRC screening practices. Religiously tailored interventions and culturally sensitive healthcare providers are needed to better promote CRC screening in South Asian Muslim communities and to help inform the design of health interventions and outreach strategies.

Journal of cancer education : the official journal of the American Association for Cancer Education · 13 citationsread the source →

Core body temperature changes in school-age children with circadian rhythm sleep-wake disorder.

Objective/background: Core body temperature (CBT) is considered a valuable marker for circadian rhythm. This study aimed to investigate the changes in CBT that are associated with the symptoms of circadian rhythm sleep-wake disorder (CRSWD) post-treatment in children. Patients/methods: Twenty-eight school-age children [10 boys and 18 girls; mean age (±standard deviation), 13.68 ± 0.93 years] who were admitted to our hospital with CRSWD underwent treatment for 6-8 weeks according to the following protocol: lights-out for sleep at 21:00; phototherapy for waking at 6:00 or 7:00; light exercise everyday (eg, a 20- to 30-min walk). CBT was continuously measured for 24 h on the first day of admission and on the first day after treatment. Results: The mean time of sleep onset/offset (±standard deviation; in hours:minutes) 1 week before admission and 1 week after treatment were 23:53 ± 2:26/9:58 ± 2:15 and 21:17 ± 0:19/6:46 ± 0:32, respectively. The mean times of sleep onset and offset measured post-treatment were significantly earlier than those measured pre-treatment (p < 0.001). The mean CBT and mean minimum CBT during sleep were significantly lower on the first day post-treatment than on the first day of admission (p = 0.011 and p < 0.001, respectively). Conclusions: Symptom improvements in patients with CRSWD were associated with a decrease in CBT during sleep, suggesting that CBT may be a biomarker for improvements in CRSWD. These results help elucidate the cause of this sleep disorder.

Sleep medicine · 6 citationsread the source →

A Professional Development Workshop to Facilitate Self-Forgiveness.

Background: Evidence suggests that forgiving one's self, others, and events improves relationships and self-esteem; reduces anxiety, depression, and stress; lowers blood pressure; improves cardiovascular health; and boosts immune function. Objective: We determined the efficacy of a workshop to facilitate forgiveness in medical education professionals. Methods: A 1-hour self-forgiveness workshop conducted by 4 facilitators was presented at a medical education conference in 2018. The workshop included a didactic presentation on forgiveness and Internal Family Systems, small group discussion on self-forgiveness concepts, a 15-minute guided imagery audio meditation on self-forgiveness, and postintervention small group discussion. The 18-item Heartland Forgiveness Scale (HFS), which measures forgiveness for self, others, and situations, was completed preintervention and postintervention (score range, 18-126). Results: There were 91 participants, including graduate medical education managers and directors (61%), deans/clerkship directors (19%), and academic faculty/others (20%). Participants were from the South (20%), West (17%), Midwest (31%), and Northeast (32%) US regions. Baseline HFS scores showed that 53% were forgiving, 47% were neutral, and no participants had unforgiving tendencies. Total HFS score significantly increased (90.31 pre versus 95.7 post, P = .013), with significant increases in forgiveness of self (53% pre versus 73% post; P = .012; odds ratio = 2.47) and forgiveness of others (49% pre versus 69% post; P = .020; odds ratio = 2.3). Preintervention group discussion topics focused on guilt, shame, and barriers to forgiving, while postintervention discussions centered on challenges and benefits. Conclusions: A brief guided meditation intervention with focused discussions was feasible and improved the immediate tendency to forgive.

Journal of graduate medical education · 2 citationsread the source →

The psychological impact of COVID-19 on Chinese healthcare workers: a systematic review and meta-analysis.

Purpose: This study aimed at investigating five dimensions of the psychological impact (post-traumatic stress symptoms (PTSS), anxiety, depression, sleep disturbance or profession-related burnout) of COVID-19 on healthcare workers (HCW) in China. Methods: Studies that evaluated at least one of the five target dimensions of the psychological impact of COVID-19 on HCW in China were included. Studies with no data of our interest were excluded. Relevant Databases were searched from inception up to June 10, 2020. Preprint articles were also included. The methodological quality was assessed using the checklist recommended by AHRQ. Both the rate of prevalence and the severity of symptoms were pooled. The protocol was registered in PROSPERO (CRD42020197126) on July 09, 2020. Results: We included 44 studies with a total of 65,706 HCW participants. Pooled prevalence rates of moderate to severe PTSS, anxiety, depression, and sleep disturbances were 27% (95% CI 16%-38%), 17% (13-21%), 15% (13-16%), and 15% (7-23%), respectively; while the prevalence of mild to severe level of PTSS, anxiety, and depression was estimated as 31% (25-37%), 37% (32-42%) and 39% (25-52%). Due to the lack of data, no analysis of profession-related burnout was pooled. Subgroup analyses indicated higher prevalence of moderate to severe psychological impact in frontline HCW, female HCW, nurses, and HCW in Wuhan. Conclusion: About a third of HCW in China showed at least one dimension of psychological symptoms during the COVID-19 pandemic, whereas the prevalence of moderate and severe syndromes was relatively low. Studies on profession-related burnout, long-term impact, and the post-stress growth are still needed.

Social psychiatry and psychiatric epidemiology · meta-analysis · 37 citationsread the source →

Effects of stress on decisions under uncertainty: A meta-analysis.

[Correction Notice: An Erratum for this article was reported in Vol 142(9) of Psychological Bulletin (see record 2016-39486-001). It should have been reported that the inverted u-shaped relationship between cortisol stress responses and decision-making performance was only observed in female, but not in male participants as suggested by the study by van den Bos, Harteveld, and Stoop (2009). Corrected versions of the affected sentences are provided.] The purpose of the present meta-analysis was to quantify the effects that stress has on decisions made under uncertainty. We hypothesized that stress increases reward seeking and risk taking through alterations of dopamine firing rates and reduces executive control by hindering optimal prefrontal cortex functioning. In certain decision situations, increased reward seeking and risk taking is dysfunctional, whereas in others, this is not the case. We also assumed that the type of stressor plays a role. In addition, moderating variables are analyzed, such as the hormonal stress response, the time between stress onset and decisions, and the participants' age and gender. We included studies in the meta-analysis that investigated decision making after a laboratory stress-induction versus a control condition (k = 32 datasets, N = 1829 participants). A random-effects model revealed that overall, stress conditions lead to decisions that can be described as more disadvantageous, more reward seeking, and more risk taking than nonstress conditions (d = .17). In those situations in which increased reward seeking and risk taking is disadvantageous, stress had significant effects (d = .26), whereas in other situations, no effects were observed (d = .01). Effects were observed under processive stressors (d = .19), but not under systemic ones (d = .09). Moderation analyses did not reveal any significant results. We concluded that stress deteriorates overall decision-making performance through the mechanisms proposed. The effects differ, depending on the decision situation and the type of stressor, but not on the characteristics of the individuals. (PsycINFO Database Record

Psychological bulletin · meta-analysis · 122 citationsread the source →

Tailored or adapted interventions for adults with chronic obstructive pulmonary disease and at least one other long-term condition: a mixed methods review.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterised by shortness of breath, cough and recurrent exacerbations. People with COPD often live with one or more co-existing long-term health conditions (comorbidities). People with more severe COPD often have a higher number of comorbidities, putting them at greater risk of morbidity and mortality. Objectives: To assess the effectiveness of any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention for people with COPD and one or more common comorbidities (quantitative data, RCTs) in terms of the following outcomes: Quality of life, exacerbations, functional status, all-cause and respiratory-related hospital admissions, mortality, pain, and depression and anxiety. To assess the effectiveness of an adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more common comorbidities (quantitative data, RCTs) compared to usual care in terms of the following outcomes: Quality of life, exacerbations, functional status, all-cause and respiratory-related hospital admissions, mortality, pain, and depression and anxiety. To identify emerging themes that describe the views and experiences of patients, carers and healthcare professionals when receiving or providing care to manage multimorbidities (qualitative data). Search methods: We searched multiple databases including the Cochrane Airways Trials Register, CENTRAL, MEDLINE, Embase, and CINAHL, to identify relevant randomised and qualitative studies. We also searched trial registries and conducted citation searches. The latest search was conducted in January 2021. Selection criteria: Eligible randomised controlled trials (RCTs) compared a) any single intervention for COPD adapted or tailored to their comorbidity(s) compared to any other intervention, or b) any adapted or tailored single COPD intervention (simple or complex) that is aimed at changing the management of people with COPD and one or more comorbidities, compared to usual care. We included qualitative studies or mixed-methods studies to identify themes. Data collection and analysis: We used standard Cochrane methods for analysis of the RCTs. We used Cochrane's risk of bias tool for the RCTs and the CASP checklist for the qualitative studies. We planned to use the Mixed Methods Appraisal tool (MMAT) to assess the risk of bias in mixed-methods studies, but we found none. We used GRADE and CERQual to assess the quality of the quantitative and qualitative evidence respectively. The primary outcome measures for this review were quality of life and exacerbations. Main results: Quantitative studies We included seven studies (1197 participants) in the quantitative analyses, with interventions including telemonitoring, pulmonary rehabilitation, treatment optimisation, water-based exercise training and case management. Interventions were either compared with usual care or with an active comparator (such as land-based exercise training). Duration of trials ranged from 4 to 52 weeks. Mean age of participants ranged from 64 to 72 years and COPD severity ranged from mild to very severe. Trials included either people with COPD and a specific comorbidity (including cardiovascular disease, metabolic syndrome, lung cancer, head or neck cancer, and musculoskeletal conditions), or with one or more comorbidities of any type. Overall, we judged the evidence presented to be of moderate to very low certainty (GRADE), mainly due to the methodological quality of included trials and imprecision of effect estimates. Intervention versus usual care Quality of life as measured by the St George's Respiratory Questionnaire (SGRQ) total score may improve with tailored pulmonary rehabilitation compared to usual care at 52 weeks (mean difference (MD) -10.85, 95% confidence interval (CI) -12.66 to -9.04; 1 study, 70 participants; low-certainty evidence). Tailored pulmonary rehabilitation is likely to improve COPD assessment test (CAT) scores compared with usual care at 52 weeks (MD -8.02, 95% CI -9.44 to -6.60; 1 study, 70 participants, moderate-certainty evidence) and with a multicomponent telehealth intervention at 52 weeks (MD -6.90, 95% CI -9.56 to -4.24; moderate-certainty evidence). Evidence is uncertain about effects of pharmacotherapy optimisation or telemonitoring interventions on CAT improvement compared with usual care. There may be little to no difference in the number of people experiencing exacerbations, or mean exacerbations with case management compared with usual care (OR 1.09, 95% CI 0.75 to 1.57; 1 study, 470 participants; very low-certainty evidence). For secondary outcomes, six-minute walk distance (6MWD) may improve with pulmonary rehabilitation, water-based exercise or multicomponent interventions at 38 to 52 weeks (low-certainty evidence). A multicomponent intervention may result in fewer people being admitted to hospital at 17 weeks, although there may be little to no difference in a telemonitoring intervention. There may be little to no difference between intervention and usual care for mortality. Intervention versus active comparator We included one study comparing water-based and land-based exercise (30 participants). We found no evidence for quality of life or exacerbations. There may be little to no difference between water- and land-based exercise for 6MWD (MD 5 metres, 95% CI -22 to 32; 38 participants; very low-certainty evidence). Qualitative studies One nested qualitative study (21 participants) explored perceptions and experiences of people with COPD and long-term conditions, and of researchers and health professionals who were involved in an RCT of telemonitoring equipment. Several themes were identified, including health status, beliefs and concerns, reliability of equipment, self-efficacy, perceived ease of use, factors affecting usefulness and perceived usefulness, attitudes and intention, self-management and changes in healthcare use. We judged the qualitative evidence presented as of very low certainty overall. Authors' conclusions: Owing to a paucity of eligible trials, as well as diversity in the intervention type, comorbidities and the outcome measures reported, we were unable to provide a robust synthesis of data. Pulmonary rehabilitation or multicomponent interventions may improve quality of life and functional status (6MWD), but the evidence is too limited to draw a robust conclusion. The key take-home message from this review is the lack of data from RCTs on treatments for people living with COPD and comorbidities. Given the variation in number and type of comorbidity(s) an individual may have, and severity of COPD, larger studies reporting individual patient data are required to determine these effects.

The Cochrane database of systematic reviews · meta-analysis · 24 citationsread the source →

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

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

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

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

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

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

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

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

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

Obesity and early cessation of breastfeeding in Denmark.

Background: Obesity is associated with early cessation of breastfeeding. Breastfeeding is multi-factorial, and several factors contribute to this association. Our aim was to investigate to what extent socio-demographic and psychosocial characteristics, parity and prenatal conditions could explain the association between high BMI and early cessation of breastfeeding. Methods: We used data from a randomized trial of 1597 Danish mothers of singleton infants. Self-reported maternal postnatal weight and height were available from 1375 (86%). High BMI was defined as body mass index ≥ 32 kg/m(2) at ~17 days after delivery. Outcome was cessation of exclusive breastfeeding by 17 weeks post-partum used in proportional hazards regression models. Results: In the unadjusted analysis, mothers with high post-partum BMI compared with other mothers had a significantly higher rate of cessation of exclusive breastfeeding, and were more frequently characterized by socio-demographic, psychosocial, perinatal and behavioural factors known to increase the risk of early breastfeeding cessation. In the adjusted analyses (n = 1226), the association between BMI and duration of exclusive breastfeeding depended on parity (P = 0.03). Among primiparae, high BMI was associated with nearly double the risk of early cessation of exclusive breastfeeding (HR = 1.74, 95% CI 1.21-2.50). Among multiparae, the association disappeared when adjusted for socio-demographic factors and previous breastfeeding experience (HR = 0.89, 95% CI 0.62-1.28). Conclusion: Parity and previous breastfeeding experience are important factors to include when studying the association between BMI and breastfeeding duration. Intervention to extend the duration of lactation among obese mothers should focus on those with no or little previous breastfeeding experience.

European journal of public health · 36 citationsread the source →

Caregiver characteristics are associated with neuropsychiatric symptoms of dementia.

Objectives: To determine whether caregiver characteristics are independently associated with neuropsychiatric symptoms of dementia (NPS) after accounting for patient characteristics. Design: Cross-sectional analysis of data from the Medicare Alzheimer's Disease Demonstration and Evaluation study. Setting: Community-dwelling residents in eight U.S. cities. Participants: Five thousand seven hundred eighty-eight patients with dementia and their caregivers. Measurements: Caregivers were asked about the presence of 12 NPS in patients with dementia. Caregiver predictors included age, sex, education, income, marital status, relationship to the patient, whether they lived with patient, number of hours per week spent caregiving, self-reported health, dependency in activities of daily living (ADLs) and instrumental activities of daily living (IADLs), depression, and burden. Multivariate linear regression was used to determine which caregiver characteristics were independently associated with reports of more NPS in patients after controlling for the patient's age, sex, dementia severity, level of ADL dependency, and dementia type. Results: Caregivers were on average 64 years old, 72% female, and 49% were the spouse of the patient (32% wives, 17% husbands). The mean burden score of caregivers was 15 (range 0-32, with higher scores indicating more burden), and 32% had significant depressive symptoms. Patients were on average 79 years old, 60% were female, and most had moderate to severe dementia. The mean number of NPS+/-standard deviation was 4.8+/-2.8. After adjusting for patient characteristics, caregivers who were younger, less educated, more depressed, more burdened, or spent more hours per week giving care reported more NPS in care recipients (all P< or =.005). Conclusion: Certain caregiver characteristics are associated with NPS, independent of patient characteristics, including dementia severity. Clinicians should consider the dynamics between patients and caregivers when managing NPS. Understanding how different caregiver characteristics influence NPS may help tailor caregiver education and interventions.

Journal of the American Geriatrics Society · 116 citationsread the source →

Repercussions of intermittent fasting on the intestinal microbiota community and body composition: a systematic review.

Context: Several therapies have been tested for combating weight gain and obesity-related metabolic diseases, and among these therapies, intermittent fasting (IF) has gained a great deal of interest. Objective: The aim of this study was to provide the reader with a current survey of IF protocols and an understanding of the outcomes found to date in terms of the profile of the intestinal microbiota (IM) in obese organisms. Data sources: Data were obtained from 4 databases: PubMed, SCOPUS, LILACs, and Web of Science. Data extraction: Data from studies relating IF protocols to the microbiota and weight loss were extracted using a protocol in START program. Data analysis: Of the 82 original articles identified from the databases, 35 were eliminated due to duplication, and 32 were excluded due to not meeting the inclusion criteria. Two additional articles found in a new search were added, yielding a total of 17 studies to be included in this review. Among the protocols, alternate-day fasting (ADF) and time-restricted feeding (TRF) were the most common, and they were shown to have different mechanisms of metabolic signaling. TRF influences weight control and biochemical parameters by regulating the circadian system, and improving satiety control systems by acting on leptin secretion. On the other hand, ADF leads to a reduction of ±75% of all energy consumption regardless of dietary composition in addition to promoting hormonal adjustments that promote weight control. Furthermore, both protocols showed the ability to remodel the IM by changing the Firmicutes/Bacteroidetes ratio and increasing the abundance of strains such as Lactobacillus spp. and Akkermansia m. that have a protective effect on metabolism against the effects of weight gain. Conclusion: In short, the ADF and TRF protocols have a positive effect on the remodeling of the IM and can possibly be used to control body adiposity, improve insulin sensitivity, and achieve other obesity-related metabolic changes.

Nutrition reviews · systematic review · 24 citationsread the source →

Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression: a systematic review and component network meta-analysis using individual participant data.

Background: Internet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom. Methods: We did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683. Findings: We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1·83 [95% credible interval (CrI) -2·90 to -0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. Interpretation: The individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package. Funding: Japan Society for the Promotion of Science.

The lancet. Psychiatry · systematic review · 158 citationsread the source →

Financial toxicity associated with a cancer diagnosis in publicly funded healthcare countries: a systematic review.

Purpose: Financial toxicity related to cancer diagnosis and treatment is a common issue in developed countries. We seek to systematically summarize the extent of the issue in very high development index countries with publicly funded healthcare. Methods: We identified articles published Jan 1, 2005, to March 7, 2019, describing financial burden/toxicity experienced by cancer patients and/or informal caregivers using OVID Medline Embase and PsychInfo, CINAHL, Business Source Complete, and EconLit databases. Only English language peer-reviewed full papers describing studies conducted in very high development index countries with predominantly publicly funded healthcare were eligible (excluded the USA). All stages of the review were evaluated in teams of two researchers excepting the final data extraction (CJL only). Results: The searches identified 7117 unique articles, 32 of which were eligible. Studies were undertaken in Canada, Australia, Ireland, UK, Germany, Denmark, Malaysia, Finland, France, South Korea, and the Netherlands. Eighteen studies reported patient/caregiver out-of-pocket costs (range US$17-US$506/month), 18 studies reported patient/caregiver lost income (range 17.6-67.3%), 14 studies reported patient/caregiver travel and accommodation costs (range US$8-US$393/month), and 6 studies reported financial stress (range 41-48%), strain (range 7-39%), or financial burden/distress/toxicity among patients/caregivers (range 22-27%). The majority of studies focused on patients, with some including caregivers. Financial toxicity was greater in those with early disease and/or more severe cancers. Conclusions: Despite government-funded universal public healthcare, financial toxicity is an issue for cancer patients and their families. Although levels of toxicity vary between countries, the findings suggest financial protection appears to be inadequate in many countries.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · systematic review · 107 citationsread the source →

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

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

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

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial.

Background: The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. Methods: DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir-ritonavir, lopinavir-ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. Findings: Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77-1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). Interpretation: No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. Funding: European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Translation: For the French translation of the abstract see Supplementary Materials section.

The Lancet. Infectious diseases · randomised controlled trial · 264 citationsread the source →

Friendship 2.0: adolescents' experiences of belonging and self-disclosure online.

This study explores the role that digital media technologies play in adolescents' experiences of friendship and identity. The author draws on findings from in-depth interviews with 32 adolescents (15 girls, 17 boys) ages 13-18 (M = 15.5 years) attending one of seven secondary schools in Bermuda. The adolescents were asked to describe the nature of their online exchanges with friends and the value they ascribe to these conversations. A thematic analysis of their responses revealed that online peer communications promote adolescents' sense of belonging and self-disclosure, two important peer processes that support identity development during adolescence. At the same time, the unique features of computer-mediated communication shape adolescents' experiences of these processes in distinct ways. Gender and age differences show that adolescents' online peer communications are not uniform; the characteristics that distinguish adolescents offline also shape their online activities.

Journal of adolescence · 60 citationsread the source →

Exercise intervention improves quality of life in older adults after myocardial infarction: randomised clinical trial.

Objective: To establish the benefits of an early, tailored and low-cost exercise intervention in older patients hospitalised for acute coronary syndrome (ACS). Methods: The study was a multicentre, randomised assessment of an exercise intervention in patients with ACS ≥70 years with reduced physical performance (as defined by the short physical performance battery (SPPB), value 4-9). The exercise intervention included four supervised sessions (1, 2, 3, 4 months after discharge) and home-based exercises. The control group attended a health education programme only. The outcomes were the 6-month and 1-year effects on physical performance, daily activities, anxiety/depression and quality of life. Finally, 1-year occurrence of adverse events was recorded. Results: Overall, 235 patients with ACS (median age 76 (73-81) years) were randomised 1 month after ACS. Exercise and control groups were well balanced. Exercise intervention improved 6-month and 1-year grip strength and gait speed. Exercise intervention was associated with a better quality of life (as measured by EuroQol-visual analogue scale at 6 months 80 (70-90) vs 70 (50-80) points, p<0.001 and at 1 year 75 (70-87) vs 65 (50-80) points, p<0.001) and with a reduced perception of anxiety and/or depression (6 months: 21% vs 42%, p=0.001; 1 year 32% vs 47%, p=0.03). The occurrence of cardiac death and hospitalisation for cardiac cause was lower in the intervention group (7.5% vs 17%, p=0.04). Conclusions: The proposed early, tailored, low-cost exercise intervention improves mobility, daily activities, quality of life and outcomes in older patients with ACS. Larger studies are needed to confirm the clinical benefit. Trial registration number: NCT03021044.

Heart (British Cardiac Society) · randomised controlled trial · 61 citationsread the source →

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

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

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

Group Intervention for Adolescent Anxiety and Depression: Outcomes of a Randomized Trial with Adolescents in Kenya.

Youth mental health interventions in low-resource communities may benefit from including empirically supported elements, using stigma-free content, and using trained lay-providers. We developed and evaluated such an intervention, targeting adolescent depression and anxiety in Kenya, where mental health care is limited by social stigma and a paucity of providers. Kenyan adolescents (N = 51, ages 14-17, 60.78% female) from a school in an urban slum in Nairobi with self-reported moderate-to-severe symptoms of depression or anxiety were randomized to the 4-week "Shamiri" ("thrive") group intervention or a study skills control intervention of equal duration. The Shamiri intervention included growth mindset, gratitude, and value affirmation exercises. The content was delivered by recent high school graduates (ages 17-21, 60% male) trained as lay-providers. Participants met in school once-a-week in groups of 9-12 youths (average group size 10). Compared to the study-skills control, Shamiri produced greater reductions in adolescent depression symptoms (p = .038; d = .32) and anxiety symptoms (p = .039; d = .54) from baseline to 4-week follow-up, and greater improvements in academic performance (p = .034; d = .32) from the school-term before versus after the intervention. There were no effects on overall social support or perceived control, but the Shamiri group showed larger increases in perceived social support from friends (p = .028, d = .71). This appears to be the first report that a brief, lay-provider delivered, community-based intervention may reduce internalizing symptoms and improve academic outcomes in high-symptom adolescents in Sub-Saharan Africa. Larger replications with extended follow-ups will help gauge the strength and durability of these effects.

Behavior therapy · randomised controlled trial · 53 citationsread the source →

Clinical Efficacy and Psychological Mechanisms of an App-Based Digital Therapeutic for Generalized Anxiety Disorder: Randomized Controlled Trial.

Background: Current treatments for generalized anxiety disorder (GAD) often yield suboptimal outcomes, partly because of insufficient targeting of underlying psychological mechanisms (eg, avoidance reinforcement learning). Mindfulness training (MT) has shown efficacy for anxiety; yet, widespread adoption has been limited, partly because of the difficulty in scaling in-person-based delivery. Digital therapeutics are emerging as potentially viable treatments; however, very few have been empirically validated. Objective: The aim of this study is to test the efficacy and mechanism of an app-delivered MT that was designed to target a potential mechanism of anxiety (reinforcement learning), based on which previous studies have shown concern regarding feedback and the perpetuation of anxiety through negative reinforcement. Methods: Individuals with GAD were recruited using social media advertisements and randomized during an in-person visit to receive treatment as usual (n=33) or treatment as usual+app-delivered MT (Unwinding Anxiety; n=32). The latter was composed of 30 modules to be completed over a 2-month period. Associated changes in outcomes were assessed using self-report questionnaires 1 and 2 months after treatment initiation. Results: We randomized 65 participants in this study, and a modified intent-to-treat approach was used for analysis. The median number of modules completed by the MT group was 25.5 (IQR 17) out of 30; 46% (13/28) of the participants completed the program. In addition, the MT group demonstrated a significant reduction in anxiety (GAD-7) compared with the control group at 2 months (67% vs 14%; median change in GAD-7: -8.5 [IQR 6.5] vs -1.0 [IQR 5.0]; P<.001; 95% CI 6-10). Increases in mindfulness at 1 month (nonreactivity subscale) mediated decreases in worry at 2 months (Penn State Worry Questionnaire; P=.02) and decreases in worry at 1 month mediated reductions in anxiety at 2 months (P=.03). Conclusions: To our knowledge, this is the first report on the efficacy and mechanism of an app-delivered MT for GAD. These findings demonstrate the clinical efficacy of MT as a digital therapeutic for individuals with anxiety (number needed to treat=1.6). These results also link recent advances in our mechanistic understanding of anxiety with treatment development, showing that app-delivered MT targets key reinforcement learning pathways, resulting in tangible, clinically meaningful reductions in worry and anxiety. Evidence-based, mechanistically targeted digital therapeutics have the potential to improve health at a population level at a low cost. Trial registration: ClinicalTrials.gov NCT03683472; https://clinicaltrials.gov/ct2/show/NCT03683472.

Journal of medical Internet research · randomised controlled trial · 26 citationsread the source →

Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study.

Background: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI -∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8-27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI -0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17-0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33-2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16-0·47] and 0·21 [0·13-0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health-Programme Hospitalier de Recherche Clinique 2010.

The lancet. Gastroenterology & hepatology · randomised controlled trial · 103 citationsread the source →

Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial.

Aims: Despite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients. Methods and results: A total of 80 patients were enrolled in this randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis as documented by MDCT (one or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels. Patients underwent an interim scan at 9 months and a final scan at 18 months with coronary computed tomographic angiography. The pre-specified primary endpoint was change in low-attenuation plaque (LAP) volume at 18 months between IPE and placebo groups. Baseline demographics, vitals, and laboratory results were not significantly different between the IPE and placebo groups; the median TG level was 259.1 ± 78.1 mg/dL. There was a significant reduction in the primary endpoint as IPE reduced LAP plaque volume by 17%, while in the placebo group LAP plaque volume more than doubled (+109%) (P = 0.0061). There were significant differences in rates of progression between IPE and placebo at study end involving other plaque volumes including fibrous, and fibrofatty (FF) plaque volumes which regressed in the IPE group and progressed in the placebo group (P < 0.01 for all). When further adjusted for age, sex, diabetes status, hypertension, and baseline TG, plaque volume changes between groups remained significantly different, P < 0.01. Only dense calcium did not show a significant difference between groups in multivariable modelling (P = 0.053). Conclusions: Icosapent ethyl demonstrated significant regression of LAP volume on MDCT compared with placebo over 18 months. EVAPORATE provides important mechanistic data on plaque characteristics that may have relevance to the REDUCE-IT results and clinical use of IPE.

European heart journal · randomised controlled trial · 334 citationsread the source →

Pharmacological interventions for somatoform disorders in adults.

Background: Somatoform disorders are characterised by chronic, medically unexplained physical symptoms (MUPS). Although different medications are part of treatment routines for people with somatoform disorders in clinics and private practices, there exists no systematic review or meta-analysis on the efficacy and tolerability of these medications. We aimed to synthesise to improve optimal treatment decisions. Objectives: To assess the effects of pharmacological interventions for somatoform disorders (specifically somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, and pain disorder) in adults. Search methods: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) (to 17 January 2014). This register includes relevant randomised controlled trials (RCTs) from The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). To identify ongoing trials, we searched ClinicalTrials.gov, Current Controlled Trials metaRegister, the World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry. For grey literature, we searched ProQuest Dissertation & Theses Database, OpenGrey, and BIOSIS Previews. We handsearched conference proceedings and reference lists of potentially relevant papers and systematic reviews and contacted experts in the field. Selection criteria: We selected RCTs or cluster RCTs of pharmacological interventions versus placebo, treatment as usual, another medication, or a combination of different medications for somatoform disorders in adults. We included people fulfilling standardised diagnostic criteria for somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, or somatoform pain disorder. Data collection and analysis: One review author and one research assistant independently extracted data and assessed risk of bias. Primary outcomes included the severity of MUPS on a continuous measure, and acceptability of treatment. Main results: We included 26 RCTs (33 reports), with 2159 participants, in the review. They examined the efficacy of different types of antidepressants, the combination of an antidepressant and an antipsychotic, antipsychotics alone, or natural products (NPs). The duration of the studies ranged between two and 12 weeks. One meta-analysis of placebo-controlled studies showed no clear evidence of a significant difference between tricyclic antidepressants (TCAs) and placebo for the outcome severity of MUPS (SMD -0.13; 95% CI -0.39 to 0.13; 2 studies, 239 participants; I(2) = 2%; low-quality evidence). For new-generation antidepressants (NGAs), there was very low-quality evidence showing they were effective in reducing the severity of MUPS (SMD -0.91; 95% CI -1.36 to -0.46; 3 studies, 243 participants; I(2) = 63%). For NPs there was low-quality evidence that they were effective in reducing the severity of MUPS (SMD -0.74; 95% CI -0.97 to -0.51; 2 studies, 322 participants; I(2) = 0%).One meta-analysis showed no clear evidence of a difference between TCAs and NGAs for severity of MUPS (SMD -0.16; 95% CI -0.55 to 0.23; 3 studies, 177 participants; I(2) = 42%; low-quality evidence). There was also no difference between NGAs and other NGAs for severity of MUPS (SMD -0.16; 95% CI -0.45 to 0.14; 4 studies, 182 participants; I(2) = 0%).Finally, one meta-analysis comparing selective serotonin reuptake inhibitors (SSRIs) with a combination of SSRIs and antipsychotics showed low-quality evidence in favour of combined treatment for severity of MUPS (SMD 0.77; 95% CI 0.32 to 1.22; 2 studies, 107 participants; I(2) = 23%).Differences regarding the acceptability of the treatment (rate of all-cause drop-outs) were neither found between NGAs and placebo (RR 1.01, 95% CI 0.64 to 1.61; 2 studies, 163 participants; I(2) = 0%; low-quality evidence) or NPs and placebo (RR 0.85, 95% CI 0.40 to 1.78; 3 studies, 506 participants; I(2) = 0%; low-quality evidence); nor between TCAs and other medication (RR 1.48, 95% CI 0.59 to 3.72; 8 studies, 556 participants; I(2) =14%; low-quality evidence); nor between antidepressants and the combination of an antidepressant and an antipsychotic (RR 0.80, 95% CI 0.25 to 2.52; 2 studies, 118 participants; I(2) = 0%; low-quality evidence). Percental attrition rates due to adverse effects were high in all antidepressant treatments (0% to 32%), but low for NPs (0% to 1.7%).The risk of bias was high in many domains across studies. Seventeen trials (65.4%) gave no information about random sequence generation and only two (7.7%) provided information about allocation concealment. Eighteen studies (69.2%) revealed a high or unclear risk in blinding participants and study personnel; 23 studies had high risk of bias relating to blinding assessors. For the comparison NGA versus placebo, there was relatively high imprecision and heterogeneity due to one outlier study. Although we identified 26 studies, each comparison only contained a few studies and small numbers of participants so the results were imprecise. Authors' conclusions: The current review found very low-quality evidence for NGAs and low-quality evidence for NPs being effective in treating somatoform symptoms in adults when compared with placebo. There was some evidence that different classes of antidepressants did not differ in efficacy; however, this was limited and of low to very low quality. These results had serious shortcomings such as the high risk of bias, strong heterogeneity in the data, and small sample sizes. Furthermore, the significant effects of antidepressant treatment have to be balanced against the relatively high rates of adverse effects. Adverse effects produced by medication can have amplifying effects on symptom perceptions, particularly in people focusing on somatic symptoms without medical causes. We can only draw conclusions about short-term efficacy of the pharmacological interventions because no trial included follow-up assessments. For each of the comparisons where there were available data on acceptability rates (NGAs versus placebo, NPs versus placebo, TCAs versus other medication, and antidepressants versus a combination of an antidepressant and an antipsychotic), no clear differences between the intervention and comparator were found. Future high-quality research should be carried out to determine the effectiveness of medications other than antidepressants, to compare antidepressants more thoroughly, and to follow-up participants over longer periods (the longest follow up was just 12 weeks). Another idea for future research would be to include other outcomes such as functional impairment or dysfunctional behaviours and cognitions as well as the classical outcomes such as symptom severity, depression, or anxiety.

The Cochrane database of systematic reviews · meta-analysis · 79 citationsread the source →

Concepts and definitions for "supportive care," "best supportive care," "palliative care," and "hospice care" in the published literature, dictionaries, and textbooks.

Purpose: Commonly used terms such as "supportive care," "best supportive care," "palliative care," and "hospice care" were rarely and inconsistently defined in the palliative oncology literature. We conducted a systematic review of the literature to further identify concepts and definitions for these terms. Methods: We searched MEDLINE, PsycInfo, EMBASE, and CINAHL for published peer-reviewed articles from 1948 to 2011 that conceptualized, defined, or examined these terms. Two researchers independently reviewed each citation for inclusion and then extracted the concepts/definitions when available. Dictionaries/textbooks were also searched. Results: Nine of 32 "SC/BSC," 25 of 182 "PC," and 12 of 42 "HC" articles focused on providing a conceptual framework/definition. Common concepts for all three terms were symptom control and quality-of-life for patients with life-limiting illness. "SC" focused more on patients on active treatment compared to other categories (9/9 vs. 8/37) and less often involved interdisciplinary care (4/9 vs. 31/37). In contrast, "HC" focused more on volunteers (6/12 vs. 6/34), bereavement care (9/12 vs. 7/34), and community care (9/12 vs. 6/34). Both "PC" and "SC/BSC" were applicable earlier in the disease trajectory (16/34 vs. 0/9). We found 13, 24, and 17 different definitions for "SC/BSC," "PC," and "HC," respectively. "SC/BSC" was the most variably defined, ranging from symptom management during cancer therapy to survivorship care. Dictionaries/textbooks showed similar findings. Conclusion: We identified defining concepts for "SC/BSC," "PC," and "HC" and developed a preliminary conceptual framework unifying these terms along the continuum of care to help build consensus toward standardized definitions.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · systematic review · 203 citationsread the source →

Progressive and interrelated functional and structural evidence of post-onset brain reduction in schizophrenia.

Context: Progressive brain abnormalities in schizophrenia remain controversial. Evidence of interrelated progressive functional impairment would buttress the case for structural progression. Mismatch negativity (MMN) is reduced in chronic but not first-hospitalized schizophrenia and may index progressive structural changes. Objective: To determine whether MMN shows associations with underlying auditory cortex gray matter at first hospitalization and progressive reduction longitudinally. Design: Cross-sectional (first hospitalization) and longitudinal (1.5-year follow-up). Setting: A private psychiatric hospital. Participants: Protocol entrance: MMN and magnetic resonance imaging at first hospitalization in 20 subjects with schizophrenia, 21 subjects with bipolar disorder with psychosis, and 32 control subjects. Longitudinal electrophysiologic testing: MMN in 16 subjects with schizophrenia, 17 subjects with bipolar disorder, and 20 control subjects. Longitudinal electrophysiologic testing and magnetic resonance imaging: MMN and magnetic resonance imaging in 11 subjects with schizophrenia, 13 subjects with bipolar disorder, and 13 control subjects. At each time point, reported samples were group matched for age, handedness, and parental socioeconomic status. Interventions: Electrophysiologic testing and high-resolution structural magnetic resonance imaging. Main outcome measures: Mismatch negativity amplitude and Heschl gyrus and planum temporale gray matter volumes. Results: Initially, groups did not differ in MMN amplitude. Subjects with schizophrenia showed associations between MMN and Heschl gyrus (r=-0.52; P=.02) not present in the other groups. At longitudinal MMN testing, schizophrenia showed MMN reduction (P=.004). Only schizophrenia evinced longitudinal left hemisphere Heschl gyrus reduction (P=.003), highly correlated with MMN reduction (r=0.6; P=.04). Conclusions: At first hospitalization for schizophrenia, MMN indexed left hemisphere Heschl gyrus gray matter volume, consistent with variable progression of pre-hospitalization cortical reduction. Longitudinally, the interrelated progressive reduction of functional and structural measures suggests progressive pathologic processes early in schizophrenia. An active process of progressive cortical reduction presents a potential therapeutic target. Mismatch negativity may be a simple, sensitive, and inexpensive index not only of this progressive pathologic process but also of successful intervention.

Archives of general psychiatry · cohort or longitudinal · 288 citationsread the source →

Internet-based intervention for smoking cessation (StopAdvisor) in people with low and high socioeconomic status: a randomised controlled trial.

Background: Internet-based interventions for smoking cessation could help millions of people stop smoking at very low unit costs; however, long-term biochemically verified evidence is scarce and such interventions might be less effective for smokers with low socioeconomic status than for those with high status because of lower online literacy to engage with websites. We aimed to assess a new interactive internet-based intervention (StopAdvisor) for smoking cessation that was designed with particular attention directed to people with low socioeconomic status. Methods: We did this online randomised controlled trial between Dec 6, 2011, and Oct 11, 2013, in the UK. Participants aged 18 years and older who smoked every day were randomly assigned (1:1) to receive treatment with StopAdvisor or an information-only website. Randomisation was automated with an unseen random number function embedded in the website to establish which treatment was revealed after the online baseline assessment. Recruitment continued until the required sample size had been achieved from both high and low socioeconomic status subpopulations. Participants, and researchers who obtained data and did laboratory analyses, were masked to treatment allocation. The primary outcome was 6 month sustained, biochemically verified abstinence. The main secondary outcome was 6 month, 7 day biochemically verified point prevalence. Analysis was by intention to treat. Homogeneity of intervention effect across the socioeconomic subsamples was first assessed to establish whether overall or separate subsample analyses were appropriate. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN99820519. Findings: We randomly assigned 4613 participants to the StopAdvisor group (n=2321) or the control group (n=2292); 2142 participants were of low socioeconomic status and 2471 participants were of high status. The overall rate of smoking cessation was similar between participants in the StopAdvisor and control groups for the primary (237 [10%] vs 220 [10%] participants; relative risk [RR] 1·06, 95% CI 0·89-1·27; p=0·49) and the secondary (358 [15%] vs 332 [15%] participants; 1·06, 0·93-1·22; p=0·37) outcomes; however, the intervention effect differed across socioeconomic status subsamples (1·44, 0·99-2·09; p=0·0562 and 1·37, 1·02-1·84; p=0·0360, respectively). StopAdvisor helped participants with low socioeconomic status stop smoking compared with the information-only website (primary outcome: 90 [8%] of 1088 vs 64 [6%] of 1054 participants; RR 1·36, 95% CI 1·00-1·86; p=0·0499; secondary outcome: 136 [13%] vs 100 [10%] participants; 1·32, 1·03-1·68, p=0·0267), but did not improve cessation rates in those with high socioeconomic status (147 [12%] of 1233 vs 156 [13%] of 1238 participants; 0·95, 0·77-1·17; p=0·61 and 222 [18%] vs 232 [19%] participants; 0·96, 0·81-1·13, p=0·64, respectively). Interpretation: StopAdvisor was more effective than an information-only website in smokers of low, but not high, socioeconomic status. StopAdvisor could be implemented easily and made freely available, which would probably improve the success rates of smokers with low socioeconomic status who are seeking online support. Funding: National Prevention Research Initiative.

The Lancet. Respiratory medicine · randomised controlled trial · 99 citationsread the source →

Efficacy of buspirone, a fundus-relaxing drug, in patients with functional dyspepsia.

Background & aims: Impaired accommodation and hypersensitivity to gastric distention are believed to be involved in the development of functional dyspepsia (FD). Buspirone, a 5-hydroxytryptamine 1A receptor agonist, relaxes the proximal stomach in healthy individuals. We studied the effects of buspirone on symptoms and mechanisms of FD. Methods: We performed a randomized, double-blind, placebo-controlled, crossover study of 17 patients (13 women; mean age, 38.5 ± 2.4 years). The study included 2 treatment periods of 4 weeks each, separated by a 2-week washout period. In the first period, 7 participants were given buspirone (10 mg, 3 times daily for 4 weeks) and 10 were given placebo 15 minutes before meals; patients switched groups for the second period. We assessed meal-related symptoms and severity, along with gastric sensitivity, accommodation, and emptying (by using barostat and breath tests) before and after 4 weeks of treatment. Results: Buspirone significantly reduced the overall severity of symptoms of dyspepsia (7.5 ± 1.3 vs 11.5 ± 1.2 for placebo; P < .005) and individual symptoms of postprandial fullness, early satiation, and upper abdominal bloating, whereas placebo had no significant effect (all P < .05). Buspirone did not alter the rate of gastric emptying of solids or sensitivity to gastric distention, but it significantly increased gastric accommodation, compared with placebo (229 ± 28 vs 141 ± 32 mL, respectively; P < .05), and delayed gastric emptying of liquids (half-life = 64 ± 5 vs 119 ± 24 minutes, respectively). Adverse events were similar when patients were given buspirone or placebo. Conclusions: In patients with FD, 4 weeks of administration of buspirone significantly improved symptoms and gastric accommodation, compared with placebo, whereas gastric emptying of liquids was delayed.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · randomised controlled trial · 188 citationsread the source →

Gatekeeper training and access to mental health care at universities and colleges.

Purpose: Gatekeeper training (GKT) programs are an increasingly popular approach to addressing access to mental health care in adolescent and young adult populations. This study evaluates the effectiveness of a widely used GKT program, Mental Health First Aid, in college student populations. Methods: A randomized control trial was conducted on 32 colleges and universities between 2009 and 2011. Campus residence halls were assigned to the intervention (Mental Health First Aid plus pre-existing trainings) or control condition (pre-existing trainings only) using matched pair randomization. The trainings were delivered to resident advisors (RAs). Outcome measures include service utilization, knowledge and attitudes about services, self-efficacy, intervention behaviors, and mental health symptoms. Data come from two sources: (1) surveys completed by the students (resident advisors and residents; N = 2,543), 2-3 months pre- and post-intervention; and (2) utilization records from campus mental health centers, aggregated by residence. Results: The training increases trainees' self-perceived knowledge (regression-adjusted effect size [ES] = .38, p < .001), self-perceived ability to identify students in distress (ES = .19, p = .01), and confidence to help (ES = .17, p = .04). There are no apparent effects, however, on utilization of mental health care in the student communities in which the trainees live. Conclusions: Although GKT programs are widely used to increase access to mental health care, these programs may require modifications to achieve their objectives.

The Journal of adolescent health : official publication of the Society for Adolescent Medicine · randomised controlled trial · 52 citationsread the source →

Impact of the Interaction Between Screen Time and Activity Interests on Adolescent Depression Risk: Construction of a Predictive Model Based on Machine Learning.

Background: Adolescent depression is an increasing public health concern, with excessive screen time elevating depression risk and activity interests providing protection. However, most studies examine these behaviors separately and rely on limited analytical methods. This study used machine learning (ML) to develop a predictive model and evaluate the combined influence of screen time and activity interests on adolescent mental health. Methods: A multi-center survey was conducted among adolescents aged 10-14 years in Chongchuan District, Nantong. Depression-related domains were assessed using the Child and Adolescent Mental Health Screening Questionnaire, integrating seven validated scales. A twostage feature-selection strategy identified 11 key predictors. Three ML models (logistic regression [LR], extreme gradient boosting [XGBoost], and categorical boosting [CatBoost]) were trained with an 80:20 stratified split. Class imbalance was addressed using synthetic minority oversampling technique and class-weighting. Model performance and interpretability were evaluated using receiver operating characteristic (ROC) and calibration curves, partial dependence plots, and shapley additive explanations (SHAP) analyses. Results: A total of 2202 valid questionnaires were analyzed. The distribution of depression severity was as follows: safe 59%, mild 17%, moderate 11%, and severe 13%. The integrated questionnaire demonstrated strong reliability (Cronbach's α = 0.910) and good construct validity (Kaiser-Meyer-Olkin [KMO] = 0.91; root mean square error of approximation [RMSEA] = 0.049; and comparative fit index [CFI] = 0.859). ROC-Youden analysis confirmed expert-defined cutoffs (29, 32, and 35). Feature selection identified 11 key predictors, with activity interest and psychological functioning consistently ranking highest in importance. Across the three ML models, LR exhibited the best generalizability, XGBoost showed overfitting, and CatBoost achieved balanced performance. SHAP and partial dependence analyses revealed nonlinear screen-time effects and dose-dependent protective effects of activity interest, including the moderation of high screen exposure in severe-risk groups. Conclusions: This study suggests that ML models can be used to screen adolescents at risk of depression by capturing the combined influence of screen time and activity interests. The model is intended for screening rather than diagnosis and may support school-based early identification, and further validation in clinical contexts is needed.

Actas espanolas de psiquiatria · cohort or longitudinalread the source →

Circadian rhythm in the assessment of postconcussion insomnia: a cross-sectional observational study.

Background: Insomnia is a major predictor of adverse outcomes in mild traumatic brain injury (mTBI), including concussion; although insomnia symptoms may be due to various sleep disorders, those related to circadian rhythm sleep-wake disorders (CRSWDs) require specific assessment and treatment. The objective of the current study was to determine the prevalence of CRSWD in a sample of treatment-seeking people with chronic insomnia symptoms after an mTBI. Methods: Participants aged 17-65 years who had experienced an mTBI and reported chronic insomnia were recruited from diverse community clinics in Ontario 3-24 months after their injury to participate in this cross-sectional observational study. Potential participants were screened by both telephone and intake interview. Exclusion criteria were alcohol or substance use disorders, preexisting brain disorder or previous neurosurgery, recent travel across more than 2 time zones or shift work. Assessments included a clinical interview, questionnaires, 2 weeks of actigraphy and a sleep diary, and a dim-light melatonin onset test. The main outcome measure was the proportion of patients with CRSWDs. Results: Of the 50 participants (32 [64%] female; median age 39.5 yr), 13 (26% [standard deviation 12%]) had an CRSWD. The most common circadian diagnosis was delayed sleep-wake phase disorder (10 participants [20%]). Interpretation: The prevalence of CRSWDs may be exceptionally high among people with chronic insomnia symptoms following mTBI. Proper detection and treatment of CRSWDs in this population is essential to facilitate recovery. The findings emphasize the relevance of a diagnostic circadian assessment in patients with mTBI presenting with chronic insomnia symptoms.

CMAJ open · cohort or longitudinal · 12 citationsread the source →

Identifying patients' support needs following critical illness: a scoping review of the qualitative literature.

Background: Intensive care survivors suffer chronic and potentially life-changing physical, psychosocial and cognitive sequelae, and supporting recovery is an international priority. As survivors' transition from the intensive care unit to home, their support needs develop and change. Methods: In this scoping review, we categorised patients' support needs using House's Social Support Needs framework (informational, emotional, instrumental, appraisal) and mapped these against the Timing it Right framework reflecting the patient's transition from intensive care (event/diagnosis) to ward (stabilisation/preparation) and discharge home (implementation/adaptation). We searched electronic databases from 2000 to 2017 for qualitative research studies reporting adult critical care survivors' experiences of care. Two reviewers independently screened, extracted and coded data. Data were analysed using a thematic framework approach. Results: From 3035 references, we included 32 studies involving 702 patients. Studies were conducted in UK and Europe (n = 17, 53%), Canada and the USA (n = 6, 19%), Australasia (n = 6, 19%), Hong Kong (n = 1, 3%), Jordan (n = 1, 3%) and multi-country (n = 1, 3%). Across the recovery trajectory, informational, emotional, instrumental, appraisal and spiritual support needs were evident, and the nature and intensity of need differed when mapped against the Timing it Right framework. Informational needs changed from needing basic facts about admission, to detail about progress and treatments and coping with long-term sequelae. The nature of emotional needs changed from needing to cope with confusion, anxiety and comfort, to a need for security and family presence, coping with flashbacks, and needing counselling and community support. Early instrumental needs ranged from managing sleep, fatigue, pain and needing nursing care and transitioned to needing physical and cognitive ability support, strength training and personal hygiene; and at home, regaining independence, strength and return to work. Appraisal needs related to obtaining feedback on progress, and after discharge, needing reassurance from others who had been through the ICU experience. Conclusions: This review is the first to identify the change in social support needs among intensive care survivors as they transition from intensive care to the home environment. An understanding of needs at different transition periods would help inform health service provision and support for survivors.

Critical care (London, England) · review · 77 citationsread the source →

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME--PART 1.

Polycystic Ovary Syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists (AACE) and the Androgen Excess and PCOS Society (AES) aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2015. PCOS has been defined using various criteria, including menstrual irregularity, hyperandrogenism, and polycystic ovary morphology (PCOM). General agreement exists among specialty society guidelines that the diagnosis of PCOS must be based on the presence of at least two of the following three criteria: chronic anovulation, hyperandrogenism (clinical or biological) and polycystic ovaries. There is need for careful clinical assessment of women's history, physical examination, and laboratory evaluation, emphasizing the accuracy and validity of the methodology used for both biochemical measurements and ovarian imaging. Free testosterone (T) levels are more sensitive than the measurement of total T for establishing the existence of androgen excess and should be ideally determined through equilibrium dialysis techniques. Value of measuring levels of androgens other than T in patients with PCOS is relatively low. New ultrasound machines allow diagnosis of PCOM in patients having at least 25 small follicles (2 to 9 mm) in the whole ovary. Ovarian size at 10 mL remains the threshold between normal and increased ovary size. Serum 17-hydroxyprogesterone and anti-Müllerian hormone are useful for determining a diagnosis of PCOS. Correct diagnosis of PCOS impacts on the likelihood of associated metabolic and cardiovascular risks and leads to appropriate intervention, depending upon the woman's age, reproductive status, and her own concerns. The management of women with PCOS should include reproductive function, as well as the care of hirsutism, alopecia, and acne. Cycle length >35 days suggests chronic anovulation, but cycle length slightly longer than normal (32 to 35 days) or slightly irregular (32 to 35-36 days) needs assessment for ovulatory dysfunction. Ovulatory dysfunction is associated with increased prevalence of endometrial hyperplasia and endometrial cancer, in addition to infertility. In PCOS, hirsutism develops gradually and intensifies with weight gain. In the neoplastic virilizing states, hirsutism is of rapid onset, usually associated with clitoromegaly and oligomenorrhea. Girls with severe acne or acne resistant to oral and topical agents, including isotretinoin (Accutane), may have a 40% likelihood of developing PCOS. Hair loss patterns are variable in women with hyperandrogenemia, typically the vertex, crown or diffuse pattern, whereas women with more severe hyperandrogenemia may see bitemporal hair loss and loss of the frontal hairline. Oral contraceptives (OCPs) can effectively lower androgens and block the effect of androgens via suppression of ovarian androgen production and by increasing sex hormone-binding globulin. Physiologic doses of dexamethasone or prednisone can directly lower adrenal androgen output. Anti-androgens can be used to block the effects of androgen in the pilosebaceous unit or in the hair follicle. Anti-androgen therapy works through competitive antagonism of the androgen receptor (spironolactone, cyproterone acetate, flutamide) or inhibition of 5α-reductase (finasteride) to prevent the conversion of T to its more potent form, 5α-dihydrotestosterone. The choice of antiandrogen therapy is guided by symptoms. The diagnosis of PCOS in adolescents is particularly challenging given significant age and developmental issues in this group. Management of infertility in women with PCOS requires an understanding of the pathophysiology of anovulation as well as currently available treatments. Many features of PCOS, including acne, menstrual irregularities, and hyperinsulinemia, are common in normal puberty. Menstrual irregularities with anovulatory cycles and varied cycle length are common due to the immaturity of the hypothalamic-pituitary-ovarian axis in the 2- to 3-year time period post-menarche. Persistent oligomenorrhea 2 to 3 years beyond menarche predicts ongoing menstrual irregularities and greater likelihood of underlying ovarian or adrenal dysfunction. In adolescent girls, large, multicystic ovaries are a common finding, so ultrasound is not a first-line investigation in women <17 years of age. Ovarian dysfunction in adolescents should be based on oligomenorrhea and/or biochemical evidence of oligo/anovulation, but there are major limitations to the sensitivity of T assays in ranges applicable to young girls. Metformin is commonly used in young girls and adolescents with PCOS as first-line monotherapy or in combination with OCPs and anti-androgen medications. In lean adolescent girls, a dose as low as 850 mg daily may be effective at reducing PCOS symptoms; in overweight and obese adolescents, dose escalation to 1.5 to 2.5 g daily is likely required. Anti-androgen therapy in adolescents could affect bone mass, although available short-term data suggest no effect on bone loss.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · guideline · 313 citationsread the source →

Latent Classes and Cumulative Impacts of Adverse Childhood Experiences.

Studies of adverse childhood experiences (ACEs) have gauged severity using a cumulative risk (CR) index. Few studies have focused on the nature of the context of adversity and their association with psychosocial outcomes. The objective of this study was to examine the patterning of ACEs and to explore the resultant patterns' association with HIV risk-taking, problem drinking, and depressive symptoms in adulthood. Latent class analysis (LCA) was used to identify homogeneous, mutually exclusive "classes" of 11 of the most commonly used ACEs. The LCA resulted in four high-risk profiles and one low-risk profile, which were labeled: (1) highly abusive and dysfunctional (3.3%; n = 1,983), (2) emotionally abusive alcoholic with parental conflict (6%, n = 3,303), (3) sexual abuse only (4.3%, n = 2,260), (4) emotionally abusive and alcoholic (30.3%, n = 17,460), and (5) normative, low risk (56.3%, n = 32,950). Compared to the low-risk class, each high-risk profile was differentially associated with adult psychosocial outcomes even when the conditional CR within that class was similar. The results further our understanding about the pattern of ACEs and the unique pathways to poor health. Implications for child welfare systems when dealing with individuals who have experienced multiple forms of early childhood maltreatment and/or household dysfunction are discussed.

Child maltreatment · 71 citationsread the source →

Perspectives on intraoperative teaching: divergence and convergence between learner and teacher.

Objective: While current emphases on operative teaching focus on "virtual" education, residents and faculty engage most intimately in the operating room. The utilization of intraoperative teaching techniques, drawn from adult education principles, is understudied. Design: A survey with both quantitative and qualitative elements was administered to surgical residents and their faculty. Thirty-eight analogous questions regarding teaching techniques, populating four general domains, were rated for frequency of application. Respondents were asked to rank best teaching practices and identify other effective educational approaches using open-ended questions. Setting: University-based general surgical residency (5 institutions). Participants: General surgical residents and their faculty. Results: 46 residents (77%) and 37 faculty (63%; mean 17 yrs experience) completed the survey. There was significant disagreement between residents and faculty in how frequently 32 of the 38 teaching techniques were applied (all p < 0.032). Faculty rated the technique "I set and communicate high standards" as the most frequently applied strategy, while residents rated "The faculty demonstrate technical consistency" the highest. The least employed approach, acknowledged by both groups, was "The faculty ask how they might improve their teaching." There were few differences between perceptions and preferences of junior vs. senior learners, and junior vs. senior faculty. Resident and faculty appreciation of most-effective teaching approaches was similar. Qualitative analysis of the open-ended questions yielded themes which resonate with both learners and teachers: communication processes, time pressures, optimization of the work/teaching environment, teacher engagement, patience/tolerance, autonomy, feedback, learner preparedness, and patient advocacy. Conclusions: The perceptions of residents and faculty regarding the frequency of using effective approaches for operative teaching are disparate. While faculty appear to value adult learning principles and perceive that they are employed regularly, residents have a discrepant viewpoint. However, themes that were identified by both residents and faculty through qualitative analysis provide the foundation for educational process improvements.

Journal of surgical education · cohort or longitudinal · 34 citationsread the source →

Intramedullary fixation of subtrochanteric fractures with long proximal femoral nail or long gamma nail: technical notes and preliminary results.

Introduction: The objective of this study was to prospectively evaluate the clinical outcome of traumatic subtrochanteric fractures fixed with long proximal femoral nail (PFN) or long gamma nail with particular emphasis on our experience of surgical techniques. Materials and methods: We reviewed the results of 49 consecutive patients who had undergone intramedullary fixation specifically with a long PFN or a long gamma nail for traumatic subtrochanteric fractures in our hospital during a 2-year period from January 2003 to December 2004. The average age of the patients was 53 years. Clinical and radiographic analyses were performed when follow-up was made at 6 weeks, 12 weeks, 6 months, 1 year and 2 years. Results: All the 49 traumatic subtrochanteric fractures healed uneventfully except 1 case of delayed union. Walking and squatting ability was completely restored in every case at follow-up examination 6 months postoperatively. Among them, 32 fractures were successfully reduced with traction on a fracture table under fluoroscopy, but cerclage wiring or cable bandage through a small incision was needed in the other 17 cases. The average operative time was 46 minutes (range, 21 to 98). Eighteen Seinsheimer type II fractures were left unlocked distally, and static distal interlocking with 1 bolt was carried out in the other 31 cases. No complications such as cutout or breakage of the implants were encountered. Conclusions: This study suggests that long PFN or long gamma nail is a reliable implant for subtrochanteric fractures, leading to high rate of bone union and minimal soft tissue damage. Intramedullary fixation has biological and biomechanical advantages, but the operation is technically demanding. Gradual learning and great patience is needed in order to make this method truly minimally invasive.

Annals of the Academy of Medicine, Singapore · cohort or longitudinal · 14 citationsread the source →

The prevalence and evidence-based management of needle fear in adults with chronic disease: A scoping review.

Background: Little is known about the prevalence and best management of needle fear in adults with chronic disease, who may experience frequent and long-term exposure to needles for lifesaving therapies such as renal dialysis and cancer treatment. Identifying interventions that assist in management of needle fear and associated distress is essential to support these patients with repeated needle and cannula exposure. Method: We followed the PRISMA methodology for scoping reviews and systematically searched PsychINFO, PubMed (MEDLINE), ProQuest, Embase and grey literature and reference lists between 1989 and October 2020 for articles related to needle discomfort, distress, anxiety, fear or phobia. The following chronic diseases were included: arthritis, asthma, chronic back pain, cancer, cardiovascular disease, chronic obstructive pulmonary disease, diabetes, and mental illness, or kidney failure. Literature concerning dentistry, vaccination, intravenous drug users and paediatric populations were excluded. Results: We identified 32 papers reporting prevalence (n = 24), management (n = 5) or both (n = 3). Needle fear prevalence varied in disease cohorts: 17-52% (cancer), 25-47% (chronic kidney disease) and 0.2-80% (diabetes). Assessment methods varied across studies. Management strategies had poor evidence-base, but included needle-specific education, decorated devices, cognitive-behavioural stress management techniques, distraction, and changing the therapy environment or modality. Conclusion: Although needle fear is common there is a paucity of evidence regarding interventions to address it among adults living with chronic disease. This scoping review has highlighted the need for improved identification of needle fear in adults and development of interventions are required for these cohorts.

PloS one · review · 61 citationsread the source →

The Assessment of Grief in Refugees and Post-conflict Survivors: A Narrative Review of Etic and Emic Research.

Background: Prolonged grief disorder (PGD) is a new mental health disorder that will be recognized by the World Health Organization's disorder classification, the ICD-11, in 2018. Current assessment measures of PGD are largely based on North American and European conceptualizations of grief (etic i.e., from the perspective of the observer). However, research is emerging from communities outside of the Global North, in particular, conflict-exposed communities, exploring local models (emic i.e., from within the cultural group), assessment measures and symptoms of grief. Several reviews have found that refugees have higher rates of mental illness, defined by etic standards as depression, post-traumatic stress disorder (PTSD), anxiety disorders and psychotic symptoms. Yet, presently there are no reviews documenting the assessment of PGD in refugees and post conflict survivors. Method: This narrative review will provide an overview of studies that assess grief in refugees to (1) identify current assessment measures of grief in refugees (i.e., type and frequency of questionnaires used, whether Global North-based, etic, or locally developed, emic, and the level of cultural adaptation) and (2) to document the variety and rate of grief symptoms identified with Global North standard measures and/or local measures (i.e., the endorsement of standard symptom items and the identification of culturally specific symptoms of grief). Results: This review revealed 24 studies that assessed disordered grief in refugee or post conflict samples. Studies were heterogeneous in their assessment methods; the majority (n = 17) used an etic approach, four used a combined etic/emic approach, and three used a predominantly emic approach. The rate of disordered grief was high depending on cultural adaptation approach (31-76%) and when standard etic measures were used the disordered grief rate was 32%. Conclusion: These findings will help to guide future studies to provide accurate assessment of grief in refugee and post conflict populations and has implications for improving cultural knowledge in clinical practice.

Frontiers in psychology · review · 39 citationsread the source →

Primary care-based interventions addressing social isolation and loneliness in older people: a scoping review.

Objectives: Primary care is well positioned to identify and address loneliness and social isolation in older adults, given its gatekeeper function in many healthcare systems. We aimed to identify and characterise loneliness and social isolation interventions and detect factors influencing implementation in primary care. Design: Scoping review using the five-step Arksey and O'Malley Framework. Data sources: MEDLINE, CINAHL, EMBASE, COCHRANE databases and grey literature were searched from inception to June 2021. Eligibility criteria: Empirical studies in English and Spanish focusing on interventions addressing social isolation and loneliness in older adults involving primary care services or professionals. Data extraction and synthesis: We extracted data on loneliness and social isolation identification strategies and the professionals involved, networks and characteristics of the interventions and barriers to and facilitators of implementation. We conducted a thematic content analysis to integrate the information extracted. Results: 32 documents were included in the review. Only seven articles (22%) reported primary care professionals screening of older adults' loneliness or social isolation, mainly through questionnaires. Several interventions showed networks between primary care, health and non-healthcare sectors, with a dominance of referral pathways (n=17). Two-thirds of reports did not provide clear theoretical frameworks, and one-third described lengths under 6 months. Workload, lack of interest and ageing-related barriers affected implementation outcomes. In contrast, well-defined pathways, collaborative designs, long-lasting and accessible interventions acted as facilitators. Conclusions: There is an apparent lack of consistency in strategies to identify lonely and socially isolated older adults. This might lead to conflicts between intervention content and participant needs. We also identified a predominance of schemes linking primary care and non-healthcare sectors. However, although professionals and participants reported the need for long-lasting interventions to create meaningful social networks, durable interventions were scarce. Sustainability should be a core outcome when implementing loneliness and social isolation interventions in primary care.

BMJ open · review · 48 citationsread the source →

Reduction in saturated fat intake for cardiovascular disease.

Background: Reducing saturated fat reduces serum cholesterol, but effects on other intermediate outcomes may be less clear. Additionally, it is unclear whether the energy from saturated fats eliminated from the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein. Objectives: To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA), monounsaturated fat (MUFA) and/or protein on mortality and cardiovascular morbidity, using all available randomised clinical trials. Search methods: We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) on 15 October 2019, and searched Clinicaltrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) on 17 October 2019. Selection criteria: Included trials fulfilled the following criteria: 1) randomised; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) compared with higher saturated fat intake or usual diet; 4) not multifactorial; 5) in adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 6) intervention duration at least 24 months; 7) mortality or cardiovascular morbidity data available. Data collection and analysis: Two review authors independently assessed inclusion, extracted study data and assessed risk of bias. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses, funnel plots and GRADE assessment. Main results: We included 15 randomised controlled trials (RCTs) (16 comparisons, ~59,000 participants), that used a variety of interventions from providing all food to advice on reducing saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of combined cardiovascular events by 21% (risk ratio (RR) 0.79; 95% confidence interval (CI) 0.66 to 0.93, 11 trials, 53,300 participants of whom 8% had a cardiovascular event, I² = 65%, GRADE moderate-quality evidence). Meta-regression suggested that greater reductions in saturated fat (reflected in greater reductions in serum cholesterol) resulted in greater reductions in risk of CVD events, explaining most heterogeneity between trials. The number needed to treat for an additional beneficial outcome (NNTB) was 56 in primary prevention trials, so 56 people need to reduce their saturated fat intake for ~four years for one person to avoid experiencing a CVD event. In secondary prevention trials, the NNTB was 32. Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate, and data on replacement with monounsaturated fat and protein was very limited. We found little or no effect of reducing saturated fat on all-cause mortality (RR 0.96; 95% CI 0.90 to 1.03; 11 trials, 55,858 participants) or cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 10 trials, 53,421 participants), both with GRADE moderate-quality evidence. There was little or no effect of reducing saturated fats on non-fatal myocardial infarction (RR 0.97, 95% CI 0.87 to 1.07) or CHD mortality (RR 0.97, 95% CI 0.82 to 1.16, both low-quality evidence), but effects on total (fatal or non-fatal) myocardial infarction, stroke and CHD events (fatal or non-fatal) were all unclear as the evidence was of very low quality. There was little or no effect on cancer mortality, cancer diagnoses, diabetes diagnosis, HDL cholesterol, serum triglycerides or blood pressure, and small reductions in weight, serum total cholesterol, LDL cholesterol and BMI. There was no evidence of harmful effects of reducing saturated fat intakes. Authors' conclusions: The findings of this updated review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events. Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies, while effects of replacement with monounsaturated fat are unclear. The reduction in combined cardiovascular events resulting from reducing saturated fat did not alter by study duration, sex or baseline level of cardiovascular risk, but greater reduction in saturated fat caused greater reductions in cardiovascular events.

The Cochrane database of systematic reviews · meta-analysis · 156 citationsread the source →

Managing Cancer And Living Meaningfully (CALM): randomised feasibility trial in patients with advanced cancer.

Background: Managing Cancer And Living Meaningfully (CALM) is a brief individual psychotherapy for patients with advanced cancer. In an intervention-only phase 2a trial, CALM showed promising results, leading to the present 2b pilot, which introduces procedures for randomisation and improved rigour in preparation for a phase 3 randomised controlled trial (RCT). Aims: To test trial methodology and assess feasibility of a confirmatory RCT. Design: A parallel-arm RCT (intervention vs usual care) with 3 and 6-month follow-ups. Assessment of feasibility included rates of consent, randomisation, attrition, intervention non-compliance and usual care contamination. Primary outcome: depressive symptoms (Patient Health Questionnaire-9; PHQ-9). Secondary outcomes: major depressive disorder (MDD), generalised anxiety, death anxiety, spiritual well-being, attachment anxiety and avoidance, self-esteem, experiential avoidance, quality of life and post-traumatic growth. Bayesian conjugate analysis was used in this low-powered setting. Setting/participants: 60 adult patients with advanced cancer from the Princess Margaret Cancer Centre. Results: Rate of consent was 32%, randomisation 78%, attrition 25%, non-compliance 37% and contamination 17%. There was support for potential treatment effects on: PHQ-9, OR=1.48, 95% Credible Interval (CRI.95) (0.65, 3.38); MDD, OR=1.56, CRI.95 (0.50, 4.84); attachment anxiety, OR=1.72, CRI.95 (0.73, 4.03); and attachment avoidance, OR=1.58, CRI.95 (0.67, 3.71). There was no support for effects on the seven remaining secondary outcomes. Conclusions: A phase 3 CALM RCT is feasible and should aim to detect effect sizes of d=0.40, with greater attention to issues of compliance and contamination. Trial registration number: NCT02353546.

BMJ supportive & palliative care · 45 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 →