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Community-based control of Aedes aegypti by adoption of eco-health methods in Chennai City, India.

Background: Dengue is highly endemic in Chennai city, South India, in spite of continuous vector control efforts. This intervention study was aimed at establishing the efficacy as well as the favouring and limiting factors relating to a community-based environmental intervention package to control the dengue vector Aedes aegypti. Methods: A cluster randomized controlled trial was designed to measure the outcome of a new vector control package and process analysis; different data collection tools were used to determine the performance. Ten randomly selected intervention clusters (neighbourhoods with 100 houses each) were paired with ten control clusters on the basis of ecological/entomological indices and sociological parameters collected during baseline studies. In the intervention clusters, Aedes control was carried out using a community-based environmental management approach like provision of water container covers through community actors, clean-up campaigns, and dissemination of dengue information through schoolchildren. The main outcome measure was reduction in pupal indices (pupae per person index), used as a proxy measure of adult vectors, in the intervention clusters compared to the control clusters. Results: At baseline, almost half the respondents did not know that dengue is serious but preventable, or that it is transmitted by mosquitoes. The stakeholder analysis showed that dengue vector control is carried out by vertically structured programmes of national, state, and local administrative bodies through fogging and larval control with temephos, without any involvement of community-based organizations, and that vector control efforts were conducted in an isolated and irregular way. The most productive container types for Aedes pupae were cement tanks, drums, and discarded containers. All ten intervention clusters with a total of 1000 houses and 4639 inhabitants received the intervention while the ten control clusters with a total of 1000 houses and 4439 inhabitants received only the routine government services and some of the information education and communication project materials. The follow-up studies showed that there was a substantial increase in dengue understanding in the intervention group with only minor knowledge changes in the control group. Community involvement and the partnership among stakeholders (particularly women's self-help groups) worked well. After 10 months of intervention, the pupae per person index was significantly reduced to 0·004 pupae per person from 1·075 (P = 0·020) in the intervention clusters compared to control clusters. There were also significant reductions in the Stegomyia indices: the house index was reduced to 4·2%, the container index to 1·05%, and the Breteau index to 4·3 from the baseline values of 19·6, 8·91, and 30·8 in the intervention arm. Conclusion: A community-based approach together with other stakeholders that promoted interventions to prevent dengue vector breeding led to a substantial reduction in dengue vector density.

Pathogens and global health · randomised controlled trial · 78 citationsread the source →

Mental health care for unaccompanied young refugees in Germany through a stepped care approach versus enhanced usual care: a cluster-randomised hybrid effectiveness-implementation trial.

Background: Unaccompanied young refugees are a vulnerable group with high rates of post-traumatic stress symptoms (PTSS). Stepped care approaches are recommended as a potential treatment framework, but research on the effectiveness of these models remains scarce. We aimed to compare a stepped care approach for unaccompanied young refugees with enhanced usual care under real-world conditions. Methods: In this cluster-randomised controlled type I hybrid implementation-effectiveness trial, we compared two active conditions, BETTER CARE and enhanced usual care, for unaccompanied young refugees in child and youth welfare service (CYWS) facilities across seven states in Germany. Eligibility criteria included age 12-20 years; arrival in Germany as unaccompanied minors; asylum application or intention; in CYWS facility care at baseline; and at least one traumatic event reported. Masking of participants was not possible due to each CYWS facility being randomly assigned to a specific treatment arm. Additionally, although study personnel were not masked to the condition, all data were self-reported and study personnel remained masked to data entry. BETTER CARE was a stepped care approach consisting of screening, prevention (via the Mein Weg [My Way] group intervention), and trauma-focused cognitive behavioural therapy (TF-CBT). Enhanced usual care included screening and a corresponding treatment recommendation. Clusters comprised one CYWS facility and were stratified and randomly assigned (1:1) using permuted blocks. Self-report questionnaires were used to assess PTSS, depressive symptoms, anxiety symptoms, and quality of life at baseline, 6 months, and 12 months. The primary outcome was a reduction in PTSS, analysed with the Child and Adolescent Trauma Screen (CATS-2) score in the intention-to-treat sample (all randomly assigned participants). The study was preregistered in the German Clinical Trials Register (DRKS00017453). Findings: The study was conducted between Oct 14, 2019, and July 27, 2023. 58 (11%) of 525 eligible facilities, including 627 unaccompanied young refugees originating from 40 countries, decided to participate and were randomly assigned. The mean age of the participants was 16·7 years (SD 1·3), with 569 (91%) identifying as male, 53 (8%) as female, and five (1%) as gender diverse. Participants reported a mean of six traumatic events (SD 3·3). 270 (43%) unaccompanied young refugees had clinically elevated levels of PTSS, and 357 (57%) were below the clinical threshold for PTSS (based on CATS-2 scores). 12 months after random assignment, there was a significant between-groups change over time effect size for PTSS in favour of BETTER CARE in the intention-to-treat sample (d=-0·17 [95% CI -0·34 to -0·004]). The dropout rate at 12 months was 38% (n=124) in BETTER CARE and 43% (n=131) in enhanced usual care. Service use and retention were low within the 12-month study period. Interpretation: This study shows the effectiveness of a stepped care model including screening, prevention, and evidence-based interventions for unaccompanied young refugees in a high-income country. The potential benefit of screening and structured care recommendations was highlighted further by improvements in the enhanced usual care condition. Dropout rates were high but similar to those in previous studies with young refugees. Future studies should address demand-side barriers to improve service use and retention. Funding: German Federal Ministry of Education and Research.

The Lancet. Global health · randomised controlled trial · 1 citationsread the source →

Effects of internet-based pain coping skills training before home exercise for individuals with hip osteoarthritis (HOPE trial): a randomised controlled trial.

This assessor-, therapist-, and participant-blinded randomised controlled trial evaluated the effects of an automated internet-based pain coping skills training (PCST) program before home exercise for people with clinically diagnosed hip osteoarthritis. One hundred forty-four people were randomised to either the PCST group or the comparator group. In the first 8 weeks, the PCST group received online education and PCST, whereas the comparison group received online education only. From weeks 8 to 24, both groups visited a physiotherapist 5 times for home exercise prescription. Assessments were performed at baseline, 8, 24, and 52 weeks. Primary outcomes were hip pain on walking (11-point numerical rating scale) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) at 24 weeks. Secondary outcomes were other measures of pain, quality-of-life, global change, self-efficacy, pain coping, pain catastrophizing, depression, anxiety, stress, physical activity, and adverse events. Primary outcomes were completed by 137 (95%), 131 (91%), and 127 (88%) participants at 8, 24, and 52 weeks, respectively. There were no significant between-group differences in primary outcomes at week 24 (change in: walking pain [mean difference 0.5 units; 95% confidence interval, -0.3 to 1.3] and function [-0.9 units; 95% confidence interval, -4.8 to 2.9]), with both groups showing clinically relevant improvements. At week 8, the PCST group had greater improvements in function, pain coping, and global improvement than comparison. Greater pain coping improvements persisted at 24 and 52 weeks. In summary, online PCST immediately improved pain coping and function but did not confer additional benefits to a subsequent exercise program, despite sustained pain coping improvements.

Pain · randomised controlled trial · 54 citationsread the source →

Mindfulness meditation alleviates depressive symptoms in women with fibromyalgia: results of a randomized clinical trial.

Objective: Depressive symptoms are common among patients with fibromyalgia, and behavioral intervention has been recommended as a major treatment component for this illness. The objective of this study was to test the effects of the Mindfulness-Based Stress Reduction (MBSR) intervention on depressive symptoms in patients with fibromyalgia. Methods: This randomized controlled trial examined effects of the 8-week MBSR intervention on depressive symptoms in 91 women with fibromyalgia who were randomly assigned to treatment (n = 51) or a waiting-list control group (n = 40). Eligible patients were at least 18 years old, willing to participate in a weekly group, and able to provide physician verification of a fibromyalgia diagnosis. Of 166 eligible participants who responded to local television news publicizing, 49 did not appear for a scheduled intake, 24 enrolled but did not provide baseline data, and 2 were excluded due to severe mental illness, leaving 91 participants. The sample averaged 48 years of age and had 14.7 years of education. The typical participant was white, married, and employed. Patients randomly assigned to treatment received MBSR. Eight weekly 2.5-hour sessions were led by a licensed clinical psychologist with mindfulness training. Somatic and cognitive symptoms of depression were assessed using the Beck Depression Inventory administered at baseline, immediately postprogram, and at followup 2 months after the conclusion of the intervention. Results: Change in depressive symptoms was assessed using slopes analyses of intervention effects over time. Depressive symptoms improved significantly in treatment versus control participants over the 3 assessments. Conclusion: This meditation-based intervention alleviated depressive symptoms among patients with fibromyalgia.

Arthritis and rheumatism · randomised controlled trial · 162 citationsread the source →

Sleep restriction therapy for insomnia is associated with reduced objective total sleep time, increased daytime somnolence, and objectively impaired vigilance: implications for the clinical management of insomnia disorder.

Study objectives: To investigate whether sleep restriction therapy (SRT) is associated with reduced objective total sleep time (TST), increased daytime somnolence, and impaired vigilance. Design: Within-subject, noncontrolled treatment investigation. Setting: Sleep research laboratory. Participants: Sixteen patients [10 female, mean age = 47.1 (10.8) y] with well-defined psychophysiological insomnia (PI), reporting TST ≤ 6 h. Interventions: Patients were treated with single-component SRT over a 4-w protocol, sleeping in the laboratory for 2 nights prior to treatment initiation and for 3 nights (SRT night 1, 8, 22) during the acute interventional phase. The psychomotor vigilance task (PVT) was completed at seven defined time points [day 0 (baseline), day 1,7,8,21,22 (acute treatment) and day 84 (3 mo)]. The Epworth Sleepiness Scale (ESS) was completed at baseline, w 1-4, and 3 mo. Measurement and results: Subjective sleep outcomes and global insomnia severity significantly improved before and after SRT. There was, however, a robust decrease in PSG-defined TST during acute implementation of SRT, by an average of 91 min on night 1, 78 min on night 8, and 69 min on night 22, relative to baseline (P < 0.001; effect size range = 1.60-1.80). During SRT, PVT lapses were significantly increased from baseline (at three of five assessment points, all P < 0.05; effect size range = 0.69-0.78), returning to baseline levels by 3 mo (P = 0.43). A similar pattern was observed for RT, with RTs slowing during acute treatment (at four of five assessment points, all P < 0.05; effect size range = 0.57-0.89) and returning to pretreatment levels at 3 mo (P = 0.78). ESS scores were increased at w 1, 2, and 3 (relative to baseline; all P < 0.05); by 3 mo, sleepiness had returned to baseline (normative) levels (P = 0.65). Conclusion: For the first time we show that acute sleep restriction therapy is associated with reduced objective total sleep time, increased daytime sleepiness, and objective performance impairment. Our data have important implications for implementation guidelines around the safe and effective delivery of cognitive behavioral therapy for insomnia.

Sleep · clinical trial · 132 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 →

Circumcision devices versus standard surgical techniques in adolescent and adult male circumcisions.

Background: Medical circumcisions are among the most common surgical procedures performed in males. The usual indications are phimosis (inability to completely retract the foreskin and expose the glans due to a congenital or acquired constriction of the prepuce), paraphimosis (when the foreskin is not pulled back over the glans after retraction resulting in a tight constricting band which causes swelling of the distal penis and acute discomfort), balanoposthitis (erythema and edema of the prepuce and glans) and balanitis (inflammation is confined to the glans; the foreskin is usually non-retractile). Circumcision devices have been developed to shorten the operative time, simplify techniques, and improve safety and cosmetic outcomes. The devices generally aim to crush the foreskin while simultaneously creating hemostasis, the foreskin is then excised or allowed to slough off. Their use is supposedly safer and easier to replicate than the standard dissection techniques. There are at least 20 devices for male circumcision on the market, yet their effectiveness has not been reviewed to date. Objectives: To assess the effects of device-based circumcisions compared with standard surgical techniques in adolescent and adult males (10 years old and above). Search methods: We performed a comprehensive search with no restrictions to the language of publication or publication status. We searched the Cochrane Library, MEDLINE (PubMed), Embase, Web of Science, trials registries, grey literature sources and conference proceedings up to 16 April 2020. Selection criteria: We included randomized controlled trials of device-based circumcisions (crush or ligature circumcision devices) compared to standard surgical dissection-based circumcision conducted by health professionals in a medical setting. Data collection and analysis: At least two review authors independently assessed study eligibility and extracted data from the included studies. We classified adverse events into serious, moderate or mild. We reported study results as risk ratios (RR) or mean differences (MD) using 95% confidence intervals (CI) and a random-effects model. We used the GRADE approach to evaluate the overall certainty of the evidence for each outcome. Main results: Eighteen trials met the inclusion criteria. Trials were conducted in China, South Africa, Kenya and Zambia, Mozambique, Rwanda, Uganda and Zimbabwe. Primary outcomes Serious adverse events: there were no serious adverse events in either treatment arm (11 trials, 3472 participants). Moderate adverse events: there may be a slight increase in moderate adverse events when devices are used compared to standard surgical techniques (RR 1.31, 95% CI 0.55 to 3.10; I²= 68%; 10 trials, 3370 participants; low-certainty evidence); this corresponds to 8 more (ranging from 15 fewer to 84 more) moderate adverse events per 1000 participants. We downgraded the certainty of the evidence for study limitations and imprecision. Secondary outcomes Mild adverse events: we are uncertain about the difference in mild adverse events between groups when devices are used compared to standard surgical techniques (RR 1.09, 95% CI 0.44 to 2.72; I² = 91%; 10 trials, 3370 participants; very low-certainty evidence). We downgraded the certainty of the evidence for study limitations, imprecision and unexplained inconsistency. Operative time: operative time is probably about 17 minutes shorter when using a device rather than standard surgical techniques, which constitutes a clinically meaningful decrease in a procedure (MD -17.26 minutes, 95% CI -19.96 to -14.57; I² = 99%; 14 trials, 4812 participants; moderate-certainty evidence). We downgraded the certainty of the evidence for serious study limitations. The standard surgical technique generally takes about 24 minutes. There may be less postoperative pain during the first 24 hours when circumcision devices are used compared to standard surgical techniques (measured using a visual analog scale [VAS]; MD 1.30 cm lower, 95% CI 2.37 lower to 0.22 lower; I² = 99%; 9 trials, 3022 participants; low-certainty evidence). We downgraded the certainty of the evidence for study limitations and unexplained heterogeneity. There may be little or no difference in postoperative pain experienced during the first seven days when compared with standard surgical techniques (measured using a VAS; MD 0.11 cm higher, 95% CI 0.89 lower to 1.11 higher; I² = 94%; 4 trials, 1430 participants; low-certainty evidence). We downgraded the certainty of the evidence for study limitations and unexplained inconsistency. A higher score on the VAS indicates greater pain. Participants may slightly prefer circumcision devices compared to standard surgical techniques (RR 1.19, 95% CI 1.04 to 1.37; I² = 97%; 15 trials, 4501 participants; low-certainty evidence). We downgraded the certainty of the evidence for study limitations and unexplained inconsistency. We recorded satisfaction as a dichotomous outcome. Higher rates reflected greater satisfaction. Authors' conclusions: We found that there were no serious adverse events reported when using a circumcision device compared to standard surgical techniques, but they may slightly increase moderate adverse effects, and it is unclear whether there is a difference in mild adverse effects. Use of circumcision devices probably reduces the time of the procedure by about 17 minutes, a clinically meaningful time saving. For patients, use of the circumcision device may result in lower pain scores during the first 24 hours and patients may be slightly more satisfied with it compared with standard surgical techniques. Clinicians, patients and policymakers can use these results in conjunction with their own contextual factors to inform the approach that best suits their healthcare settings. High-quality trials evaluating this intervention are needed to provide further certainty regarding the rates of adverse effects and postoperative pain of using devices compared to standard approaches.

The Cochrane database of systematic reviews · meta-analysis · 15 citationsread the source →

Educational and psychological interventions for managing atopic dermatitis (eczema).

Background: Atopic dermatitis (eczema), can have a significant impact on well-being and quality of life for affected people and their families. Standard treatment is avoidance of triggers or irritants and regular application of emollients and topical steroids or calcineurin inhibitors. Thorough physical and psychological assessment is central to good-quality treatment. Overcoming barriers to provision of holistic treatment in dermatological practice is dependent on evaluation of the efficacy and economics of both psychological and educational interventions in this participant group. This review is based on a previous Cochrane review published in 2014, and now includes adults as well as children. Objectives: To assess the clinical outcomes of educational and psychological interventions in children and adults with atopic dermatitis (eczema) and to summarise the availability and principal findings of relevant economic evaluations. Search methods: We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, APA PsycINFO and two trials registers up to March 2023. We checked the reference lists of included studies and related systematic reviews for further references to relevant randomised controlled trials (RCTs) and contacted experts in the field to identify additional studies. We searched NHS Economic Evaluation Database, MEDLINE and Embase for economic evaluations on 8 June 2022. Selection criteria: Randomised, cluster-randomised and cross-over RCTs that assess educational and psychological interventions for treating eczema in children and adults. Data collection and analysis: We used standard Cochrane methods, with GRADE to assess the certainty of the evidence for each outcome. Primary outcomes were reduction in disease severity, as measured by clinical signs, patient-reported symptoms and improvement in health-related quality-of-life (HRQoL) measures. Secondary outcomes were improvement in long-term control of symptoms, improvement in psychological well-being, improvement in standard treatment concordance and adverse events. We assessed short- (up to 16 weeks after treatment) and long-term time points (more than 16 weeks). Main results: We included 37 trials (6170 participants). Most trials were conducted in high-income countries (34/37), in outpatient settings (25/37). We judged three trials to be low risk of bias across all domains. Fifteen trials had a high risk of bias in at least one domain, mostly due to bias in measurement of the outcome. Trials assessed interventions compared to standard care. Individual educational interventions may reduce short-term clinical signs (measured by SCORing Atopic Dermatitis (SCORAD); mean difference (MD) -5.70, 95% confidence interval (CI) -9.39 to -2.01; 1 trial, 30 participants; low-certainty evidence) but patient-reported symptoms, HRQoL, long-term eczema control and psychological well-being were not reported. Group education interventions probably reduce clinical signs (SCORAD) both in the short term (MD -9.66, 95% CI -19.04 to -0.29; 3 studies, 731 participants; moderate-certainty evidence) and the long term (MD -7.22, 95% CI -11.01 to -3.43; 3 studies, 1424 participants; moderate-certainty evidence) and probably reduce long-term patient-reported symptoms (SMD -0.47 95% CI -0.60 to -0.33; 2 studies, 908 participants; moderate-certainty evidence). They may slightly improve short-term HRQoL (SMD -0.19, 95% CI -0.36 to -0.01; 4 studies, 746 participants; low-certainty evidence), but may make little or no difference to short-term psychological well-being (Perceived Stress Scale (PSS); MD -2.47, 95% CI -5.16 to 0.22; 1 study, 80 participants; low-certainty evidence). Long-term eczema control was not reported. We don't know whether technology-mediated educational interventions could improve short-term clinical signs (SCORAD; 1 study; 29 participants; very low-certainty evidence). They may have little or no effect on short-term patient-reported symptoms (Patient Oriented Eczema Measure (POEM); MD -0.76, 95% CI -1.84 to 0.33; 2 studies; 195 participants; low-certainty evidence) and probably have little or no effect on short-term HRQoL (MD 0, 95% CI -0.03 to 0.03; 2 studies, 430 participants; moderate-certainty evidence). Technology-mediated education interventions probably slightly improve long-term eczema control (Recap of atopic eczema (RECAP); MD -1.5, 95% CI -3.13 to 0.13; 1 study, 232 participants; moderate-certainty evidence), and may improve short-term psychological well-being (MD -1.78, 95% CI -2.13 to -1.43; 1 study, 24 participants; low-certainty evidence). Habit reversal treatment may reduce short-term clinical signs (SCORAD; MD -6.57, 95% CI -13.04 to -0.1; 1 study, 33 participants; low-certainty evidence) but we are uncertain about any effects on short-term HRQoL (Children's Dermatology Life Quality Index (CDLQI); 1 study, 30 participants; very low-certainty evidence). Patient-reported symptoms, long-term eczema control and psychological well-being were not reported. We are uncertain whether arousal reduction therapy interventions could improve short-term clinical signs (Eczema Area and Severity Index (EASI); 1 study, 24 participants; very low-certainty evidence) or patient-reported symptoms (visual analogue scale (VAS); 1 study, 18 participants; very low-certainty evidence). Arousal reduction therapy may improve short-term HRQoL (Dermatitis Family Impact (DFI); MD -2.1, 95% CI -4.41 to 0.21; 1 study, 91 participants; low-certainty evidence) and psychological well-being (PSS; MD -1.2, 95% CI -3.38 to 0.98; 1 study, 91 participants; low-certainty evidence). Long-term eczema control was not reported. No studies reported standard care compared with self-help psychological interventions, psychological therapies or printed education; or adverse events. We identified two health economic studies. One found that a 12-week, technology-mediated, educational-support programme may be cost neutral. The other found that a nurse practitioner group-education intervention may have lower costs than standard care provided by a dermatologist, with comparable effectiveness. Authors' conclusions: In-person, individual education, as an adjunct to conventional topical therapy, may reduce short-term eczema signs compared to standard care, but there is no information on eczema symptoms, quality of life or long-term outcomes. Group education probably reduces eczema signs and symptoms in the long term and may also improve quality of life in the short term. Favourable effects were also reported for technology-mediated education, habit reversal treatment and arousal reduction therapy. All favourable effects are of uncertain clinical significance, since they may not exceed the minimal clinically important difference (MCID) for the outcome measures used (MCID 8.7 points for SCORAD, 3.4 points for POEM). We found no trials of self-help psychological interventions, psychological therapies or printed education. Future trials should include more diverse populations, address shared priorities, evaluate long-term outcomes and ensure patients are involved in trial design.

The Cochrane database of systematic reviews · meta-analysis · 14 citationsread the source →

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

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

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

Alcoholics Anonymous and other 12-step programs for alcohol use disorder.

Background: Alcohol use disorder (AUD) confers a prodigious burden of disease, disability, premature mortality, and high economic costs from lost productivity, accidents, violence, incarceration, and increased healthcare utilization. For over 80 years, Alcoholics Anonymous (AA) has been a widespread AUD recovery organization, with millions of members and treatment free at the point of access, but it is only recently that rigorous research on its effectiveness has been conducted. Objectives: To evaluate whether peer-led AA and professionally-delivered treatments that facilitate AA involvement (Twelve-Step Facilitation (TSF) interventions) achieve important outcomes, specifically: abstinence, reduced drinking intensity, reduced alcohol-related consequences, alcohol addiction severity, and healthcare cost offsets. Search methods: We searched the Cochrane Drugs and Alcohol Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, CINAHL and PsycINFO from inception to 2 August 2019. We searched for ongoing and unpublished studies via ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 15 November 2018. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and bibliographies of included studies. Selection criteria: We included randomized controlled trials (RCTs), quasi-RCTs and non-randomized studies that compared AA or TSF (AA/TSF) with other interventions, such as motivational enhancement therapy (MET) or cognitive behavioral therapy (CBT), TSF treatment variants, or no treatment. We also included healthcare cost offset studies. Participants were non-coerced adults with AUD. Data collection and analysis: We categorized studies by: study design (RCT/quasi-RCT; non-randomized; economic); degree of standardized manualization (all interventions manualized versus some/none); and comparison intervention type (i.e. whether AA/TSF was compared to an intervention with a different theoretical orientation or an AA/TSF intervention that varied in style or intensity). For analyses, we followed Cochrane methodology calculating the standard mean difference (SMD) for continuous variables (e.g. percent days abstinent (PDA)) or the relative risk (risk ratios (RRs)) for dichotomous variables. We conducted random-effects meta-analyses to pool effects wherever possible. Main results: We included 27 studies containing 10,565 participants (21 RCTs/quasi-RCTs, 5 non-randomized, and 1 purely economic study). The average age of participants within studies ranged from 34.2 to 51.0 years. AA/TSF was compared with psychological clinical interventions, such as MET and CBT, and other 12-step program variants. We rated selection bias as being at high risk in 11 of the 27 included studies, unclear in three, and as low risk in 13. We rated risk of attrition bias as high risk in nine studies, unclear in 14, and low in four, due to moderate (> 20%) attrition rates in the study overall (8 studies), or in study treatment group (1 study). Risk of bias due to inadequate researcher blinding was high in one study, unclear in 22, and low in four. Risks of bias arising from the remaining domains were predominantly low or unclear. AA/TSF (manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) RCTs comparing manualized AA/TSF to other clinical interventions (e.g. CBT), showed AA/TSF improves rates of continuous abstinence at 12 months (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 2 studies, 1936 participants; high-certainty evidence). This effect remained consistent at both 24 and 36 months. For percentage days abstinent (PDA), AA/TSF appears to perform as well as other clinical interventions at 12 months (mean difference (MD) 3.03, 95% CI -4.36 to 10.43; 4 studies, 1999 participants; very low-certainty evidence), and better at 24 months (MD 12.91, 95% CI 7.55 to 18.29; 2 studies, 302 participants; low-certainty evidence) and 36 months (MD 6.64, 95% CI 1.54 to 11.75; 1 study, 806 participants; low-certainty evidence). For longest period of abstinence (LPA), AA/TSF may perform as well as comparison interventions at six months (MD 0.60, 95% CI -0.30 to 1.50; 2 studies, 136 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at 12 months, as measured by drinks per drinking day (DDD) (MD -0.17, 95% CI -1.11 to 0.77; 1 study, 1516 participants; moderate-certainty evidence) and percentage days heavy drinking (PDHD) (MD -5.51, 95% CI -14.15 to 3.13; 1 study, 91 participants; low-certainty evidence). For alcohol-related consequences, AA/TSF probably performs as well as other clinical interventions at 12 months (MD -2.88, 95% CI -6.81 to 1.04; 3 studies, 1762 participants; moderate-certainty evidence). For alcohol addiction severity, one study found evidence of a difference in favor of AA/TSF at 12 months (P < 0.05; low-certainty evidence). AA/TSF (non-manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) For the proportion of participants completely abstinent, non-manualized AA/TSF may perform as well as other clinical interventions at three to nine months follow-up (RR 1.71, 95% CI 0.70 to 4.18; 1 study, 93 participants; low-certainty evidence). Non-manualized AA/TSF may also perform slightly better than other clinical interventions for PDA (MD 3.00, 95% CI 0.31 to 5.69; 1 study, 93 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at nine months, as measured by DDD (MD -1.76, 95% CI -2.23 to -1.29; 1 study, 93 participants; very low-certainty evidence) and PDHD (MD 2.09, 95% CI -1.24 to 5.42; 1 study, 286 participants; low-certainty evidence). None of the RCTs comparing non-manualized AA/TSF to other clinical interventions assessed LPA, alcohol-related consequences, or alcohol addiction severity. Cost-effectiveness studies In three studies, AA/TSF had higher healthcare cost savings than outpatient treatment, CBT, and no AA/TSF treatment. The fourth study found that total medical care costs decreased for participants attending CBT, MET, and AA/TSF treatment, but that among participants with worse prognostic characteristics AA/TSF had higher potential cost savings than MET (moderate-certainty evidence). Authors' conclusions: There is high quality evidence that manualized AA/TSF interventions are more effective than other established treatments, such as CBT, for increasing abstinence. Non-manualized AA/TSF may perform as well as these other established treatments. AA/TSF interventions, both manualized and non-manualized, may be at least as effective as other treatments for other alcohol-related outcomes. AA/TSF probably produces substantial healthcare cost savings among people with alcohol use disorder.

The Cochrane database of systematic reviews · meta-analysis · 192 citationsread the source →

Allostatic load and frailty in the women's health and aging studies.

Background: Frailty involves decrements in many physiologic systems, is prevalent in older ages, and is characterized by increased vulnerability to disability and mortality. It is yet unclear how this geriatric syndrome relates to a preclinical cumulative marker of multisystem dysregulation. The purpose of this study was to evaluate whether allostatic load (AL) was associated with the geriatric syndrome of frailty in older community-dwelling women. Methods: We examined the cross-sectional relationship between AL and a validated measure of frailty in the baseline examination of two complementary population-based cohort studies, the Women's Health and Aging studies (WHAS) I and II. This sample of 728 women had an age range of 70-79. We used ordinal logistic regression to estimate the relationship between AL and frailty controlling for covariates. Results: About 10% of women were frail and 46% were prefrail. AL ranged from 0 to 8 with 91% of participants scoring between 0 and 4. Regression models showed that a unit increase in the AL score was associated with increasing levels of frailty (OR = 1.16, 95% CI = 1.04-1.28) controlling for race, age, education, smoking status, and comorbidities. Conclusion: This study suggests that frailty is associated with AL. The observed relationship provides some support for the hypothesis that accumulation of physiological dysregulation may be related to the loss of reserve characterized by frailty.

Biological research for nursing · 70 citationsread the source →

Physiological Profiles During Delay of Gratification: Associations with Emotionality, Self-regulation, and Adjustment Problems.

This longitudinal study utilized a community sample of children (N=91, 45% female, 8-11 years at time 1) to investigate physiological responses (heart rate reactivity [HRR] and electrodermal responding [EDR]) during delay of gratification in relation to emotionality, self-regulation, and adjustment problems. Cluster analyses identified three profiles among children who successfully delayed: children who waited easily with low EDR and moderate HRR, children who had difficulty waiting with high EDR and moderate HRR, and children who had difficulty waiting with low EDR and low HRR. The 3 clusters and children who did not wait were compared. Children with low EDR-low HRR had the lowest self-regulation, and like the no-wait group, demonstrated the greatest baseline adjustment problems. The high EDR-moderate HRR group demonstrated highest self-regulation and increases in depression across one year. Distinct profiles among children in delay contexts point to children who are over- and under-regulated with implications for adjustment problems.

Journal of applied developmental psychology · 69 citationsread the source →

Long-term developmental effects of withholding parenteral nutrition for 1 week in the paediatric intensive care unit: a 2-year follow-up of the PEPaNIC international, randomised, controlled trial.

Background: The paediatric early versus late parenteral nutrition in critical illness (PEPaNIC) multicentre, randomised, controlled trial showed that, compared with early parenteral nutrition, withholding supplemental parenteral nutrition for 1 week in the paediatric intensive care unit (PICU; late parenteral nutrition) reduced infections and accelerated recovery from critical illness in children. We aimed to investigate the long-term impact on physical and neurocognitive development of early versus late parenteral nutrition. Methods: In this preplanned 2-year follow-up study, all patients included in the PEPaNIC trial (which was done in University Hospitals Leuven, Belgium; Erasmus Medical Centre-Sophia Children's Hospital, Rotterdam, Netherlands; and Stollery Children's Hospital, Edmonton, AB, Canada) were approached for possible assessment of physical and neurocognitive development compared with healthy children who were matched for age and sex, and who had never been admitted to a neonatal ICU or a PICU. Assessed outcomes comprised anthropometric data; health status; parent-reported or caregiver-reported executive functions and emotional and behavioural problems; and tests for intelligence, visual-motor integration, alertness, motor coordination, inhibitory control, cognitive flexibility, and memory. To address partial responses among the children tested, we did multiple data imputation by chained equations before univariable and multivariable linear and logistic regression analyses adjusted for risk factors. This trial is registered with ClinicalTrials.gov, number NCT01536275. Findings: At the 2-year follow-up, 60 (8%) of 717 children who received late parenteral nutrition and 63 (9%) of 723 children who received early parenteral nutrition had died (p=0·81). 68 (9%) of 717 children who received late and 91 (13%) of 723 children who received early parenteral nutrition were too disabled for neurocognitive assessment (p=0·059), and 786 patients (395 assigned to late and 391 assigned to early parenteral nutrition) consented for testing. 786 patients and 405 healthy control children underwent long-term outcome testing between Aug 4, 2014, and Jan 19, 2018, and were included in the imputation model for subsequent multivariable analyses. Late parenteral nutrition did not adversely affect anthropometric data, health status, or neurological functioning, and improved parent-reported or caregiver-reported executive functioning (late vs early parenteral nutrition β estimate -2·258, 95% CI -4·012 to -0·504; p=0·011), more specifically inhibition (-3·422, -5·171 to -1·673; p=0·0001), working memory (-2·016, -3·761 to -0·270; p=0·023), and meta-cognition (-1·957, -3·694 to -0·220; p=0·027). Externalising behavioural problems (β estimate -1·715, 95% CI -3·325 to -0·106; p=0·036) and visual-motor integration (0·468, 0·087 to 0·850; p=0·016) were also improved in the late parenteral nutrition group compared with the early parenteral nutrition group. After Bonferroni correction for multiple comparisons, the effect on inhibitory control remained significant (p=0·0001). Interpretation: Withholding early parenteral nutrition for 1 week in the PICU did not negatively affect survival, anthropometrics, health status, and neurocognitive development, and improved inhibitory control 2 years after PICU admission. Funding: European Research Council Advanced Grant, Methusalem programme provided by the Flemish Government, Flemish Agency for Innovation by Science and Technology (IWT), Research Foundation Flanders (FWO), Sophia Children's Hospital Foundation (SSWO), Stichting Agis Zorginnovatie, Erasmus Trustfonds, and European Society for Parenteral and Enteral Nutrition (ESPEN) research grant.

The Lancet. Respiratory medicine · randomised controlled trial · 72 citationsread the source →

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT.

Background: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. Objective: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? Design: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. Settings: Glasgow, UK, and Melbourne, Australia. Participants: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. Interventions: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. Main outcome measures: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. Results: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference -4.29, 95% confidence interval -7.29 to -1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. Limitations: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. Conclusions: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible. Future work: A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4). Trial registration: This trial is registered as ISRCTN99559262. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879).

Health technology assessment (Winchester, England) · randomised controlled trial · 24 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 →

Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial.

Importance: Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. Objective: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. Design, setting, and participants: An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. Interventions: The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. Main outcomes and measures: Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). Results: Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). Conclusions and relevance: Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Trial registration: clinicaltrials.gov Identifier: NCT00179777.

JAMA · randomised controlled trial · 97 citationsread the source →

Bilateral versus unilateral cochlear implants in children: a study of spoken language outcomes.

Objectives: Although it has been established that bilateral cochlear implants (CIs) offer additional speech perception and localization benefits to many children with severe to profound hearing loss, whether these improved perceptual abilities facilitate significantly better language development has not yet been clearly established. The aims of this study were to compare language abilities of children having unilateral and bilateral CIs to quantify the rate of any improvement in language attributable to bilateral CIs and to document other predictors of language development in children with CIs. Design: The receptive vocabulary and language development of 91 children was assessed when they were aged either 5 or 8 years old by using the Peabody Picture Vocabulary Test (fourth edition), and either the Preschool Language Scales (fourth edition) or the Clinical Evaluation of Language Fundamentals (fourth edition), respectively. Cognitive ability, parent involvement in children's intervention or education programs, and family reading habits were also evaluated. Language outcomes were examined by using linear regression analyses. The influence of elements of parenting style, child characteristics, and family background as predictors of outcomes were examined. Results: Children using bilateral CIs achieved significantly better vocabulary outcomes and significantly higher scores on the Core and Expressive Language subscales of the Clinical Evaluation of Language Fundamentals (fourth edition) than did comparable children with unilateral CIs. Scores on the Preschool Language Scales (fourth edition) did not differ significantly between children with unilateral and bilateral CIs. Bilateral CI use was found to predict significantly faster rates of vocabulary and language development than unilateral CI use; the magnitude of this effect was moderated by child age at activation of the bilateral CI. In terms of parenting style, high levels of parental involvement, low amounts of screen time, and more time spent by adults reading to children facilitated significantly better vocabulary and language outcomes. In terms of child characteristics, higher cognitive ability and female sex were predictive of significantly better language outcomes. When family background factors were examined, having tertiary-educated primary caregivers and a family history of hearing loss were significantly predictive of better outcomes. Birth order was also found to have a significant negative effect on both vocabulary and language outcomes, with each older sibling predicting a 5 to 10% decrease in scores. Conclusions: Children with bilateral CIs achieved significantly better vocabulary outcomes, and 8-year-old children with bilateral CIs had significantly better language outcomes than did children with unilateral CIs. These improvements were moderated by children's ages at both first and second CIs. The outcomes were also significantly predicted by a number of factors related to parenting, child characteristics, and family background. Fifty-one percent of the variance in vocabulary outcomes and between 59 to 69% of the variance in language outcomes was predicted by the regression models.

Ear and hearing · cohort or longitudinal · 81 citationsread the source →

Behavioural, educational and respiratory outcomes of antenatal betamethasone for term caesarean section (ASTECS trial).

Objectives: To determine whether antenatal betamethasone prior to elective term caesarean section (CS) affects long term behavioural, cognitive or developmental outcome, and whether the risk of asthma or atopic disease is reduced. Design: A questionnaire based follow-up of a multicentre randomised controlled trial (Antenatal Steroids for Term Elective Caesarean Section, BMJ 2005). Setting: Four UK study centres from the original trial. Participants: 862 participants from the four largest recruiting centres, 92% of the original study. 824 (96%) were traced and 799 (93%) were successfully contacted. Fifty-one percent (407/799) completed and returned the questionnaire. The children were aged 8-15 years (median 12.2 years, 52% girls). 386 gave consent to contact schools with 352 (91%) reports received. Main outcome measures: Questionnaires including a strengths and difficulties questionnaire, International Study of Asthma and Allergies in Childhood, general health and school performance. Results: There were no significant differences between children whose mothers received betamethasone and controls for the mean total strengths and difficulties questionnaire scores and subscores for hyperactivity, emotional symptoms, prosocial behaviour, conduct or peer problems. 25 (12%) children whose mothers received betamethasone had reported learning difficulties compared with 27 (14%) control children. The proportion of children who achieved standard assessment tests KS2 exams level 4 or above for mathematics, English or science was similar as were the rates of ever reported wheeze (30% vs 30%), asthma (24% vs 21%), eczema (34% vs 37%) and hay fever (25% vs 27%). Conclusions: Antenatal betamethasone did not result in any adverse outcomes or reduction in asthma or atopy. It should be considered for elective CS at 37-38 weeks of gestation. Trial registration: : Original trial was preregistration, the trial publication is BMJ. 2005 Sep 24;331(7518):662.

Archives of disease in childhood. Fetal and neonatal edition · randomised controlled trial · 105 citationsread the source →

A school-based expressive writing intervention for at-risk urban adolescents' aggressive behavior and emotional lability.

This school-based randomized controlled trial tested the efficacy of 2 expressive writing interventions among youth living in high-violence urban neighborhoods. Seventeen classrooms (n = 258 seventh graders; 55% female; 91% African American/Black) from 3 public schools were randomized to 3 conditions in which they wrote 8 times about a nonemotional topic (control condition) or about experiencing and witnessing violence following either a standard or an enhanced expressive writing protocol. Outcomes were assessed 1 month prior and 2 and 6 months postintervention and included teacher-rated emotional lability and aggressive behavior and child-rated physical aggression. Intent-to-treat, mixed-model analyses controlled for preintervention measures of outcomes, sex, race, and family structure. At 2 months postintervention, relative to controls, students in the standard expressive writing condition had lower levels of teacher-rated aggression and lability (d = -.48). The beneficial effects of the writing interventions on aggression and lability were stronger at higher levels of community violence exposure.

Journal of clinical child and adolescent psychology : the official journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53 · randomised controlled trial · 17 citationsread the source →

Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: A nonrandomized controlled pilot study.

Background: Depression presents a significant burden to both patients and society. One treatment that has emerged is vagus nerve stimulation (VNS), an FDA-approved physical treatment for depressive disorders. However, the application of this intervention has been limited by the involvement of surgery and potential side effects. The aim of this study is to explore the effectiveness of stimulating the superficial branches of the vagus nerve as a solo treatment for MDD. Methods: This is a nonrandomized, controlled study. The first cohort of patients (n=91) only received transcutaneous auricular VNS (taVNS) for 12 weeks. In the second cohort (n=69), patients first received 4 weeks of sham taVNS followed by 8 weeks of taVNS. All treatments were self-administered by the patients at home after they received training from the hospitals. The primary outcome measurement was the 24-item Hamilton Depression Rating Scale measured at weeks 0, 4, 8, and 12. Data analysis included a timelag analysis comparing (1) real and sham taVNS groups at week 4; (2) the real taVNS group at week 4 vs the sham taVNS group at week 8 (fourth week of real taVNS following 4 weeks of sham); and (3) the real taVNS group at week 8 vs the sham taVNS group at week 12 (eighth week of real taVNS following sham). Results: After four weeks of treatment, MDD patients in the taVNS group showed greater improvement than patients in the sham taVNS group as indicated by Hamilton score changes as well as response and remission rates at week four. In addition, we also found that the clinical improvements continued until week 12 during taVNS. Limitations: Patients were not randomized in this study. Conclusions: Our results suggest that taVNS is a promising, safe, and cost-effective therapeutic method for mild and moderate MDD.

Journal of affective disorders · clinical trial · 210 citationsread the source →

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

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

European urology · clinical trial · 222 citationsread the source →

Feasibility Study of Stress Management and Resiliency Training (SMART) in Patients With Major Depressive Disorder.

Objective: Stress is associated with the onset, maintenance, and recurrence of depression. This study investigated the feasibility of stress management and resiliency training (SMART) for enhancing resiliency in a group of patients with major depressive disorder. Methods: In an open-label study, patients with major depressive disorder were invited to participate in an adjunctive 8-week group therapy of SMART (from June 2017 to June 2018) that encompassed attention training and practice of gratitude, compassion, higher meaning, acceptance, and forgiveness. The primary outcome measure was baseline-to-endpoint change in resilience as measured by the Connor Davidson Resilience Scale (CD-RISC). Secondary outcome measures included baseline-to-endpoint change in stress using the Perceived Stress Scale (PSS) and in depression using the 17-item Hamilton Depression Rating Scale (HDRS-17) and 9-item Patient Health Questionnaire (PHQ-9). Results: Twenty-three participants enrolled in the study (mean ± SD age = 46 ± 13 years, female = 91%). Baseline ratings of mood were of mild-to-moderate symptom severity (mean HDRS-17 score = 14.5 and PHQ-9 score = 12), resilience (mean CD-RISC score = 53.8), and perceived stress (mean PSS score = 23.5). Of the participants, 74% were study completers (attended ≥ 6 sessions). In an intention-to-treat analysis, at study endpoint there was a significant improvement in resilience (mean CD-RISC score = 61.1, P = .03), reduction in perceived stress (mean PSS score = 19.4, P = .002), and improvement in depression (mean HDRS-17 score = 9.1 and PHQ-9 score = 7.6, both P < .001). Conclusions: A resilience training program focused on wellness is feasible for patients who are currently symptomatic with major depressive disorder. A larger randomized controlled trial is needed to establish efficacy of this intervention and explore the long-term impact of stress management and resilience training in depression. Trial registration: ClinicalTrials.gov identifier: NCT03275961.

The primary care companion for CNS disorders · clinical trial · 9 citationsread the source →

Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: a randomized controlled trial.

Context: Studies of depressed psychiatric patients have shown that antidepressant efficacy can be increased by augmentation with omega-3 fatty acids. Objective: To determine whether omega-3 improves the response to sertraline in patients with major depression and coronary heart disease (CHD). Design, setting, and participants: Randomized controlled trial. Between May 2005 and December 2008, 122 patients in St Louis, Missouri, with major depression and CHD were randomized. Interventions: After a 2-week run-in period, all patients were given 50 mg/d of sertraline and randomized in double-blind fashion to receive 2 g/d of omega-3 acid ethyl esters (930 mg of eicosapentaenoic acid [EPA] and 750 mg of docosahexaenoic acid [DHA]) (n=62) or to corn oil placebo capsules (n=60) for 10 weeks. Main outcome measures: Scores on the Beck Depression Inventory (BDI-II) and the Hamilton Rating Scale for Depression (HAM-D). Results: Adherence to the medication regimen was 97% or more in both groups for both medications. There were no differences in weekly BDI-II scores (treatment x time interaction = 0.02; 95% confidence interval [CI], -0.33 to 0.36; t(112) = 0.11; P = .91), pre-post BDI-II scores (placebo, 14.8 vs omega-3, 16.1; 95% difference-in-means CI, -4.5 to 2.0; t(116) = -0.77; P = .44), or HAM-D scores (placebo, 9.4 vs omega-3, 9.3; 95% difference-in-means CI, -2.2 to 2.4; t(115) = 0.12; P = .90). The groups did not differ on predefined indicators of depression remission (BDI-II < or = 8: placebo, 27.4% vs omega-3, 28.3%; odds ratio [OR], 0.96; 95% CI, 0.43-2.15; t(113) = -0.11; P = .91) or response (> 50% reduction in BDI-II from baseline: placebo, 49.0% vs omega-3, 47.7%; OR, 1.06; 95% CI, 0.51-2.19; t(112) = 0.15; P = .88). Conclusions: Treatment of patients with CHD and major depression with sertraline and omega-3 fatty acids did not result in superior depression outcomes at 10 weeks, compared with sertraline and placebo. Whether higher doses of omega-3 or sertraline, a different ratio of EPA to DHA, longer treatment, or omega-3 monotherapy can improve depression in patients with CHD remains to be determined. Trial registration: clinicaltrials.gov Identifier: NCT00116857.

JAMA · randomised controlled trial · 91 citationsread the source →

Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial.

Background: Lack of education and an economic dependence on men are often suggested as important risk factors for HIV infection in women. We assessed the efficacy of a cash transfer programme to reduce the risk of sexually transmitted infections in young women. Methods: In this cluster randomised trial, never-married women aged 13-22 years were recruited from 176 enumeration areas in the Zomba district of Malawi and randomly assigned with computer-generated random numbers by enumeration area (1:1) to receive cash payments (intervention group) or nothing (control group). Intervention enumeration areas were further randomly assigned with computer-generated random numbers to conditional (school attendance required to receive payment) and unconditional (no requirements to receive payment) groups. Participants in both intervention groups were randomly assigned by a lottery to receive monthly payments ranging from US$1 to $5, while their parents were independently assigned with computer-generated random numbers to receive $4-10. Behavioural risk assessments were done at baseline and 12 months; serology was tested at 18 months. Participants were not masked to treatment status but counsellors doing the serologic testing were. The primary outcomes were prevalence of HIV and herpes simplex virus 2 (HSV-2) at 18 months and were assessed by intention-to-treat analyses. The trial is registered, number NCT01333826. Findings: 88 enumeration areas were assigned to receive the intervention and 88 as controls. For the 1289 individuals enrolled in school at baseline with complete interview and biomarker data, weighted HIV prevalence at 18 month follow-up was 1·2% (seven of 490 participants) in the combined intervention group versus 3·0% (17 of 799 participants) in the control group (adjusted odds ratio [OR] 0·36, 95% CI 0·14-0·91); weighted HSV-2 prevalence was 0·7% (five of 488 participants) versus 3·0% (27 of 796 participants; adjusted OR 0·24, 0·09-0·65). In the intervention group, we noted no difference between conditional versus unconditional intervention groups for weighted HIV prevalence (3/235 [1%] vs 4/255 [2%]) or weighted HSV-2 prevalence (4/233 [1%] vs 1/255 [<1%]). For individuals who had already dropped out of school at baseline, we detected no significant difference between intervention and control groups for weighted HIV prevalence (23/210 [10%] vs 17/207 [8%]) or weighted HSV-2 prevalence (17/211 [8%] vs 17/208 [8%]). Interpretation: Cash transfer programmes can reduce HIV and HSV-2 infections in adolescent schoolgirls in low-income settings. Structural interventions that do not directly target sexual behaviour change can be important components of HIV prevention strategies. Funding: Global Development Network, Bill & Melinda Gates Foundation, National Bureau of Economic Research Africa Project, World Bank's Research Support Budget, and several World Bank trust funds (Gender Action Plan, Knowledge for Change Program, and Spanish Impact Evaluation fund).

Lancet (London, England) · randomised controlled trial · 389 citationsread the source →

Cyber bullying and internalizing difficulties: above and beyond the impact of traditional forms of bullying.

Although recent research has demonstrated significant links between involvement in cyber bullying and various internalizing difficulties, there exists debate as to whether these links are independent of involvement in more traditional forms of bullying. The present study systematically examined the association between involvement in cyber bullying, as either a victim or a bully, and both depressive symptomatology and suicidal ideation. Self-report data were collected from 399 (57% female) Canadian adolescents in grades 8-10 (mean age = 14.2 years, SD = .91 years). Results indicated that involvement in cyber bullying, as either a victim or a bully, uniquely contributed to the prediction of both depressive symptomatology and suicidal ideation, over and above the contribution of involvement in traditional forms of bullying (physical, verbal, relational). Given the ever increasing rate of accessibility to technology in both schools and homes, these finding underscore the importance of addressing cyber bullying, with respect to both research and intervention, as a unique phenomenon with equally unique challenges for students, parents, school administrators and researchers alike.

Journal of youth and adolescence · 151 citationsread the source →

Dose-dependent and joint associations between screen time, physical activity, and mental wellbeing in adolescents: an international observational study.

Background: Mental wellbeing in adolescents has declined considerably during past decades, making the identification of modifiable risk factors important. Prolonged screen time and insufficient physical activity appear to operate independently and synergistically to increase the risk of poor mental wellbeing in school-aged children. We aimed to examine the gender-stratified dose-dependent and joint associations of screen time and physical activity with mental wellbeing in adolescents. Methods: We used data from three rounds of Health Behaviour in School-aged Children cross-sectional surveys (2006, 2010, and 2014) from 42 European and North American countries. Survey participants, aged 11 years, 13 years, and 15 years, provided self-reported information by completing an anonymous questionnaire that included items on health indicators and related behaviours. We used the self-reported variables of life satisfaction and psychosomatic complaints as indicators of adolescents' mental wellbeing, combining these with the self-reported discretionary use of screens and engagement in physical activity. We used generalised additive models and multilevel regression modelling to examine the gender-stratified relationships between mental wellbeing and screen time and physical activity. Findings: Our sample included 577 475 adolescents (mean age 13·60 years, SD 1·64), with 296 542 (51·35%) girls and 280 933 (48·64%) boys. The mean reported life satisfaction score (on a scale of 0-10) was 7·70 (95% CI 7·69-7·71) in boys and 7·48 (7·46-7·50) in girls. Psychosomatic complaints were more common among girls (mean 9·26, 95% CI 9·23-9·28) than boys (6·89, 6·87-6·91). Generalised additive model analyses showed slightly non-linear associations of screen time and physical activity with life satisfaction and psychosomatic complaints for girls and boys. Detrimental associations between screen time and mental wellbeing started when screen time exceeded 1 h per day, whereas increases in physical activity levels were beneficially and monotonically associated with wellbeing. Multilevel modelling showed that screen time levels were negatively associated with life satisfaction and positively associated with psychosomatic complaints in a dose-dependent manner. Physical activity levels were positively associated with life satisfaction and negatively associated with psychosomatic complaints in a dose-dependent manner. Joint associations of screen time-physical activity with mental wellbeing showed that, compared with the least active participants with more than 8 h per day of screen time and no physical activity, most of the other screen time-physical activity groups had considerably higher life satisfaction and lower psychosomatic complaints. Interpretation: Higher levels of screen time and lower levels of physical activity were associated with lower life satisfaction and higher psychosomatic complaints among adolescents from high-income countries. Public health strategies to promote adolescents' mental wellbeing should aim to decrease screen time and increase physical activity simultaneously. Funding: None.

The Lancet. Child & adolescent health · cohort or longitudinal · 63 citationsread the source →

Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines.

Background: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. Objectives: To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. Methods: The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events. Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Pain physician · guideline · 225 citationsread the source →

Advance care planning beyond advance directives: perspectives from patients and surrogates.

Context: Advance care planning (ACP) has focused on documenting life-sustaining treatment preferences in advance directives (ADs). The ADs alone may be insufficient to prepare diverse patients and surrogates for complex medical decisions. Objectives: To understand what steps best prepare patients and surrogates for decision making. Methods: We conducted 13 English/Spanish focus groups with participants from a Veterans Affairs and county hospital and the community. Seven groups included patients (n=38), aged ≥65 years, who reported making serious medical decisions. Six separate groups included surrogates (n=31), aged ≥18 years, who made decisions for others. Semistructured focus groups asked what activities best prepared the participants for decision making. Two investigators independently coded data and performed thematic content analysis. Disputes were resolved by consensus. Results: The mean±SD patient age was 78±8 years, and 61% were nonwhite. The mean±SD surrogate age was 57±10 years, and 91% were nonwhite. Qualitative analysis identified four overarching themes about how to best prepare for decision making: 1) identify values based on past experiences and quality of life, 2) choose surrogates wisely and verify that they understand their role, 3) decide whether to grant leeway in surrogate decision making, and 4) inform other family and friends of one's wishes to prevent conflict. Conclusion: Beyond ADs, patients and surrogates recommend several additional steps to prepare for medical decision making including using past experiences to identify values, verifying that the surrogate understands their role, deciding whether to grant surrogates leeway, and informing other family and friends of one's wishes. Future ACP interventions should consider incorporating these additional ACP activities.

Journal of pain and symptom management · cohort or longitudinal · 142 citationsread the source →

Characteristics of U.S. Veterans Who Begin and Complete Prolonged Exposure and Cognitive Processing Therapy for PTSD

This retrospective chart-review study examined patient-level correlates of initiation and completion of evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) among treatment-seeking U.S. veterans. We identified all patients (N = 796) in a large Veterans Affairs PTSD and anxiety clinic who attended at least 1 individual psychotherapy appointment with 1 of 8 providers trained in EBP. Within this group, 91 patients (11.4%) began EBP (either Cognitive Processing Therapy or Prolonged Exposure) and 59 patients (7.9%) completed EBP. The medical records of all EBP patients (n = 91) and a provider-matched sample of patients who received another form of individual psychotherapy (n = 66) were reviewed by 4 independent raters. Logistic regression analyses revealed that Iraq and Afghanistan veterans were less likely to begin EBP than veterans from other service eras, OR = 0.48, 95% CI = [0.24, 0.94], and veterans who were service connected for PTSD were more likely than veterans without service connection to begin EBP, OR = 2.33, 95% CI = [1.09, 5.03]. Among those who began EBP, Iraq and Afghanistan veteran status, OR = 0.09, 95% CI = [0.03, 0.30], and a history of psychiatric inpatient hospitalization, OR = 0.13, 95% CI = [0.03, 0.54], were associated with decreased likelihood of EBP completion.

Journal of Traumatic Stress · 165 citationsread the source →

Autism Spectrum Disorder: A Review.

Importance: Autism spectrum disorder (ASD), characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests, is a neurodevelopmental disorder affecting approximately 2.3% children aged 8 years in the US and approximately 2.2% of adults. This review summarizes evidence on the diagnosis and treatment of ASD. Observations: The estimated prevalence of ASD has been increasing in the US, from 1.1% in 2008 to 2.3% in 2018, which is likely associated with changes in diagnostic criteria, improved performance of screening and diagnostic tools, and increased public awareness. No biomarkers specific to the diagnosis of ASD have been identified. Common early signs and symptoms of ASD in a child's first 2 years of life include no response to name when called, no or limited use of gestures in communication, and lack of imaginative play. The criterion standard for the diagnosis of ASD is a comprehensive evaluation with a multidisciplinary team of clinicians and is based on semistructured direct observation of the child's behavior and semistructured caregiver interview focused on the individual's development and behaviors using standardized measures, such as the Autism Diagnostic Observation Schedule-Second Edition and the Autism Diagnostic Interview. These diagnostic measures have sensitivity of 91% and 80% and specificity of 76% and 72%, respectively. Compared with people without ASD, individuals with ASD have higher rates of depression (20% vs 7%), anxiety (11% vs 5%), sleep difficulties (13% vs 5%), and epilepsy (21% with co-occurring intellectual disability vs 0.8%). Intensive behavioral interventions, such as the Early Start Denver Model, are beneficial in children 5 years or younger for improvement in language, play, and social communication (small to medium effect size based on standardized mean difference). Pharmacotherapy is indicated for co-occurring psychiatric conditions, such as emotion dysregulation or attention-deficit/hyperactivity disorder. Risperidone and aripiprazole can improve irritability and aggression (standardized mean difference of 1.1, consistent with a large effect size) compared with placebo. Psychostimulants are effective for attention-deficit/hyperactivity disorder (standardized mean difference of 0.6, consistent with a moderate effect size) compared with placebo. These medications are associated with adverse effects including, most commonly, changes in appetite, weight, and sleep. Conclusions and relevance: ASD affects approximately 2.3% of children aged 8 years and approximately 2.2% of adults in the US. First-line therapy consists of behavioral interventions, while co-occurring psychiatric conditions, such as anxiety or aggression, may be treated with specific behavioral therapy or medication.

JAMA · review · 467 citationsread the source →

Botulinum toxin type A in the treatment of lower limb spasticity in children with cerebral palsy.

Background: Cerebral palsy (CP) is the most common cause of physical disabilities in children in high-income countries. Spasticity is the most common motor disturbance in CP. Botulinum toxin type A (BoNT-A) is considered the first-line treatment for focal spasticity in people with CP. Objectives: To evaluate the effectiveness and safety of BoNT-A compared to other treatments used in the management of lower limb spasticity in children with CP. Search methods: We searched CENTRAL, PubMed, four other databases, and two trial registers in October 2018. We also searched the reference lists of relevant studies and reviews and contacted experts in the field. We did not apply any date or language restrictions. Selection criteria: Randomised controlled trials of children with CP, aged between birth and 19 years, treated with BoNT-A injections in the lower limb muscles compared to other interventions. The primary outcomes were gait analysis and function. The secondary outcomes were joint range of motion, quality of life, satisfaction, spasticity, and adverse events. Data collection and analysis: Two review authors independently selected studies, extracted data, assessed risk of bias, and rated the quality of the evidence using GRADE. A third review author arbitrated in case of disagreements. We conducted meta-analyses of available data whenever possible, analysing dichotomous data with risk ratios (RR), and continuous data with mean differences (MD) or standardised mean differences (SMD), with 95% confidence intervals (CI). We considered a 5% significance level for all analyses. Whenever possible, we analysed outcomes at the time points at which they were assessed: short term (2 to 8 weeks); medium term (12 to 16 weeks); and long term (> 24 weeks). Main results: We included 31 randomised controlled trials assessing 1508 participants. Most studies included ambulatory patients with more than one motor type of CP, and with a mean age of between three and seven years. There was a slight predominance of males. Studies compared BoNT-A in the lower limb muscles to usual care or physiotherapy (14 studies), placebo or sham (12 studies), serial casting (4 studies), or orthoses (1 study).We rated studies as at high or unclear risk of bias mainly due to random sequence generation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment. BoNT-A versus usual care or physiotherapyBoNT-A might improve overall gait scores at medium-term follow-up (MD 2.80, 95% CI 1.55 to 4.05; 1 study, 40 children; very low-quality evidence) and is moderately effective at improving function at short-term (SMD 0.59, 95% CI 0.23 to 0.95; 2 studies, 123 children) and medium-term (SMD 1.04, 95% CI 0.16 to 1.91; 4 studies, 191 children) follow-up (all very low-quality evidence).BoNT-A improves ankle range of motion, satisfaction, and ankle plantarflexors spasticity at one or more time points (very low-quality evidence).The proportion of adverse events in the BoNT-A group was 0.37 (95% CI 0.08 to 0.66; I2 = 95%; very low-quality evidence). No adverse events were reported in the control group. BoNT-A versus placebo or shamBoNT-A improves overall gait scores at short-term (RR 1.66, 95% CI 1.16 to 2.37, P = 0.006; 4 studies, 261 assessments) and medium-term (RR 1.90, 95% CI 1.32 to 2.74, P < 0.001; 3 studies, 248 assessments) follow-up, and may improve peak ankle dorsiflexion in stance (MD 15.90 degrees, 95% CI 4.87 to 26.93, P = 0.005; 1 study, 19 children) and in swing (MD 10.20 degrees, 95% CI 4.01 to 16.39, P = 0.001; 1 study, 19 children) at short-term follow-up (all moderate-quality evidence).BoNT-A is not more effective than placebo or sham at improving function at short-term (SMD 0.24, 95% CI -0.35 to 0.83, P = 0.42; 4 studies, 305 children) or long-term (SMD -0.07, 95% CI -0.48 to 0.35, P = 0.76; 2 studies, 91 children) follow-up, but has a small positive effect at medium-term follow-up (SMD 0.28, 95% CI 0.06 to 0.49, P = 0.01; 5 studies, 327 children) (all moderate-quality evidence).BoNT-A improves passive ankle range of motion, satisfaction, and ankle plantarflexors spasticity at one or more time points (moderate-quality evidence).There was no difference between groups in the rate of adverse events at short-term follow-up (RR 1.29, 95% CI 0.87 to 1.93, P = 0.21; 12 studies, 918 children; moderate-quality evidence).BoNT-A versus serial castingThere was no difference between groups for overall gait scores at short-term (MD 0.00, 95% CI -1.66 to 1.66); medium-term (MD 0.65, 95% CI -1.21 to 2.51); or long-term (MD 0.46, 95% CI -1.33 to 2.25) follow-up in one study with 18 children (moderate-quality evidence).BoNT-A improved instrumented gait analysis only in terms of ankle dorsiflexion at initial contact (MD 6.59 degrees, 95% CI 1.39 to 11.78, P = 0.01; 2 studies, 47 children). There was no difference between groups for peak ankle dorsiflexion in stance and swing, and gait speed at any time point (moderate- and low-quality evidence).BoNT-A is not more effective than serial casting at improving function, ankle range of motion, and spasticity at any time point (moderate- and low-quality evidence).BoNT-A is not associated with a higher risk of adverse events than serial casting (RR 0.59, 95% CI 0.03 to 11.03; 3 studies, 64 children; low-quality evidence).BoNT-A versus orthosesThere was no difference between groups for function at medium-term follow-up (MD 11.14, 95% CI -0.05 to 22.33; 1 study, 43 children), but BoNT-A is more effective than orthoses at improving hip range of motion and hip adductors spasticity (all very low-quality evidence). Authors' conclusions: The quality of the evidence was low or very low for most of the outcomes analysed. We found limited evidence that BoNT-A is more effective than placebo or a non-placebo control at improving gait, joint range of motion, satisfaction, and lower limb spasticity in children with CP, whereas the results for function were contradictory. The rate of adverse events with BoNT-A is similar to placebo. BoNT-A is not more effective than ankle serial casting to treat ankle contractures for any of the assessed outcomes, but is more effective than orthotics at improving range of motion and spasticity.

The Cochrane database of systematic reviews · review · 38 citationsread the source →

Early Bereavement Psychosocial Outcomes in Parents of Children Who Died of Cancer With a Focus on Social Functioning

PURPOSE: The early grief experience of parents of children who died of cancer remains understudied. Understanding psychosocial symptomology and functioning of parents early in their bereavement is essential to developing supportive interventions aimed at offsetting poor mental and physical outcomes. METHODS: Parents of children from two centers who died of cancer 6 to 24 months before were mailed a survey that included validated tools and additional Likert scale-based questions. We used correlation and univariate and multiple regression analyses to assess the associations between psychosocial and grief outcomes and parental social functioning. RESULTS: One hundred twenty-five parents representing 88 children completed the survey. Most respondents identified as female (63%), White (84%), and non-Hispanic (91%). The mean time since child's death was 14.7 (range, 8-26) months. Bereaved parents' mean score for social functioning was only slightly below normative values, and most parents indicated post-traumatic growth and adaptive coping. Parents had high symptom levels for depression, anxiety, post-traumatic stress, and prolonged grief, with those identifying as female having significantly higher symptom scores. Using multivariate analysis, parental scores for resilience and continuing bonds were associated with higher social functioning scores and parental scores for depressive symptoms and prolonged grief were associated with lower social functioning scores. CONCLUSION: Although bereaved parents exhibit resilience and positive coping, they also show high levels of psychosocial distress in the first 2 years after their child's death, which may reflect the typical parental bereavement experience. Screening for low parental social functioning may identify parents who would benefit from additional support early in bereavement.

JCO Oncology Practice · 24 citationsread the source →

Development and Validation of a Prediction Model for Kidney Failure in Long-Term Survivors of Childhood Cancer.

Purpose: Kidney failure is a rare but serious late effect following treatment for childhood cancer. We developed a model using demographic and treatment characteristics to predict individual risk of kidney failure among 5-year survivors of childhood cancer. Methods: Five-year survivors from the Childhood Cancer Survivor Study (CCSS) without history of kidney failure (n = 25,483) were assessed for subsequent kidney failure (ie, dialysis, kidney transplantation, or kidney-related death) by age 40 years. Outcomes were identified by self-report and linkage with the Organ Procurement and Transplantation Network and the National Death Index. A sibling cohort (n = 5,045) served as a comparator. Piecewise exponential models accounting for race/ethnicity, age at diagnosis, nephrectomy, chemotherapy, radiotherapy, congenital genitourinary anomalies, and early-onset hypertension estimated the relationships between potential predictors and kidney failure, using area under the curve (AUC) and concordance (C) statistic to evaluate predictive power. Regression coefficient estimates were converted to integer risk scores. The St Jude Lifetime Cohort Study and the National Wilms Tumor Study served as validation cohorts. Results: Among CCSS survivors, 204 developed late kidney failure. Prediction models achieved an AUC of 0.65-0.67 and a C-statistic of 0.68-0.69 for kidney failure by age 40 years. Validation cohort AUC and C-statistics were 0.88/0.88 for the St Jude Lifetime Cohort Study (n = 8) and 0.67/0.64 for the National Wilms Tumor Study (n = 91). Risk scores were collapsed to form statistically distinct low- (n = 17,762), moderate- (n = 3,784), and high-risk (n = 716) groups, corresponding to cumulative incidences in CCSS of kidney failure by age 40 years of 0.6% (95% CI, 0.4 to 0.7), 2.1% (95% CI, 1.5 to 2.9), and 7.5% (95% CI, 4.3 to 11.6), respectively, compared with 0.2% (95% CI, 0.1 to 0.5) among siblings. Conclusion: Prediction models accurately identify childhood cancer survivors at low, moderate, and high risk for late kidney failure and may inform screening and interventional strategies.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 15 citationsread the source →

Predicting postoperative pulmonary complications: implications for outcomes and costs.

Purpose of review: This review of progress toward reliable prediction of postoperative pulmonary complications (PPCs) discusses risk assessment against the background of patient management strategies, clinical outcomes, and cost of healthcare. Recent findings: Among the variety of conditions grouped as PPCs are pneumonia, aspiration pneumonitis, respiratory failure, reintubation within 48 h, weaning failure, pleural effusion, atelectasis, bronchospasm, and pneumothorax. PPC incidence rates range from 2 to 40% depending on context. These events increase mortality, postoperative length of stay, ICU admissions, hospital readmissions, and costs. PPC-associated mortality varies, but can reach as high as 48% in some contexts. ICU admission rates are between 9.5 and 91% higher in patients with PPCs. The mean increase in PPC-related postoperative length of stay is approximately 8 days. The cost of surgery can be two-fold to 12-fold higher when PPCs develop. Strategies proposed to reduce the impact of modifiable risk factors include alcohol and smoking abstinence before surgery, shortening the duration of surgery, and physiotherapy and incentive spirometry techniques; however, little scientific evidence supports them at this time. Summary: PPCs are associated with a higher incidence of life-threatening events and higher costs. Reliable PPC risk-stratification tools are essential for guiding clinical decision-making in the perioperative period. The care team can act on modifiable factors and optimize vigilance over nonmodifiable ones. It would be useful to focus resources on determining whether low-cost preemptive interventions improve outcomes satisfactorily or new strategies need to be developed.

Current opinion in anaesthesiology · review · 126 citationsread the source →

How Do Corticosteroids Work in Asthma?

Reviews2 September 2003How Do Corticosteroids Work in Asthma?Peter J. Barnes, DM, DSc and Ian M. Adcock, PhDPeter J. Barnes, DM, DScFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this author and Ian M. Adcock, PhDFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-5_Part_1-200309020-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesAsthma is the most common chronic disease in westernized countries. Patients with asthma have an underlying chronic inflammation of the airways characterized by activated mast cells, eosinophils, and T-helper 2 lymphocytes. This results in increased responsiveness of the airways to such triggers as exercise, allergens, and air pollutants. This chronic inflammation underlies the typical symptoms of asthma, which include intermittent wheezing, coughing, shortness of breath, and chest tightness. Corticosteroids are the most effective treatment for asthma, and inhaled corticosteroids have become first-line treatment for children and adults with persistent symptoms. Corticosteroids suppress the chronic airway inflammation in patients with asthma, and the molecular ...References1. Busse WW, Lemanske RF. Asthma. N Engl J Med. 2001;344:350-62. [PMID: 11172168] CrossrefMedlineGoogle Scholar2. Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998;50:515-96. [PMID: 9860804] MedlineGoogle Scholar3. Barnes PJ, Adcock IM. Transcription factors and asthma. Eur Respir J. 1998;12:221-34. [PMID: 9701442] CrossrefMedlineGoogle Scholar4. Hart LA, Krishnan VL, Adcock IM, Barnes PJ, Chung KF. Activation and localization of transcription factor, nuclear factor-B, in asthma. 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Molecular regulation of granulocyte macrophage colony-stimulating factor in human lung epithelial cells by interleukin (IL)-1, IL-4, and IL-13 involves both transcriptional and post-transcriptional mechanisms. Am J Respir Cell Mol Biol. 2000;22:582-9. [PMID: 10783130] CrossrefMedlineGoogle Scholar37. Caelles C, Gonzalez-Sancho JM, Munoz A. Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 1997;11:3351-64. [PMID: 9407028] CrossrefMedlineGoogle Scholar38. Vanden Berghe W, Vermeulen L, De Wilde G, De Bosscher K, Boone E, Haegeman G. Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol. 2000;60:1185-95. [PMID: 11007957] CrossrefMedlineGoogle Scholar39. Lasa M, Brook M, Saklatvala J, Clark AR. Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. Mol Cell Biol. 2001;21:771-80. [PMID: 11154265] CrossrefMedlineGoogle Scholar40. Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR. Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38. Mol Cell Biol. 2002;22:7802-11. [PMID: 12391149] CrossrefMedlineGoogle Scholar41. Barnes PJ. Scientific rationale for inhaled combination therapy with long-acting 2-agonists and corticosteroids. Eur Respir J. 2002;19:182-91. [PMID: 11843317] CrossrefMedlineGoogle Scholar42. Adcock IM, Stevens DA, Barnes PJ. Interactions of glucocorticoids and 2-agonists. Eur Respir J. 1996;9:160-8. [PMID: 8834349] CrossrefMedlineGoogle Scholar43. Mak JC, Nishikawa M, Shirasaki H, Miyayasu K, Barnes PJ. Protective effects of a glucocorticoid on downregulation of pulmonary 2-adrenergic receptors in vivo. J Clin Invest. 1995;96:99-106. [PMID: 7615841] CrossrefMedlineGoogle Scholar44. Mak JC, Hisada T, Salmon M, Barnes PJ, Chung KF. Glucocorticoids reverse IL-1-induced impairment of -adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinases. Br J Pharmacol. 2002;135:987-96. [PMID: 11861327] CrossrefMedlineGoogle Scholar45. Eickelberg O, Roth M, Lorx R, Bruce V, Rudiger J, Johnson M, . Ligand-independent activation of the glucocorticoid receptor by 2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem. 1999;274:1005-10. [PMID: 9873044] CrossrefMedlineGoogle Scholar46. Pang L, Knox AJ. Regulation of TNF--induced eotaxin release from cultured human airway smooth muscle cells by 2-agonists and corticosteroids. FASEB J. 2001;15:261-269. [PMID: 11149914] CrossrefMedlineGoogle Scholar47. Korn SH, Wouters EF, Wesseling G, Arends JW, Thunnissen FB. Interaction between glucocorticoids and 2-agonists: and glucocorticoid-receptor mRNA expression in human bronchial epithelial cells. Biochem Pharmacol. 1998;56:1561-9. [PMID: 9973176] CrossrefMedlineGoogle Scholar48. Usmani OS, Maneechotesuwan K, Adcock IM, Barnes PJ. Glucocorticoid receptor activation following inhaled fluticasone and salmeterol [Abstract]. Am J Respir Crit Care Med. 2002;165:A616. Google Scholar49. Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med. 2003;167:813-8. [PMID: 12623857] CrossrefMedlineGoogle Scholar50. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, . A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci U S A. 2002;99:8921-6. [PMID: 12070353] CrossrefMedlineGoogle Scholar51. Evans DJ, Taylor DA, Zetterstrom O, Chung KF, O'Connor BJ, Barnes PJ. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med. 1997;337:1412-8. [PMID: 9358138] CrossrefMedlineGoogle Scholar52. Ukena D, Harnest U, Sakalauskas R, Magyar P, Vetter N, Steffen H, . Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma. Eur Respir J. 1997;10:2754-60. [PMID: 9493656] CrossrefMedlineGoogle Scholar53. Lim S, Jatakanon A, Gordon D, Macdonald C, Chung KF, Barnes PJ. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice. Thorax. 2000;55:837-41. [PMID: 10992535] CrossrefMedlineGoogle Scholar54. Szefler SJ, Leung DY. Glucocorticoid-resistant asthma: pathogenesis and clinical implications for management. Eur Respir J. 1997;10:1640-7. [PMID: 9230260] CrossrefMedlineGoogle Scholar55. Barnes PJ. Steroid-resistant asthma. Eur Resp Rev. 2000;10:74-8. Google Scholar56. Spahn JD, Szefler SJ, Surs W, Doherty DE, Nimmagadda SR, Leung DY. A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity. J Immunol. 1996;157:2654-9. [PMID: 8805670] MedlineGoogle Scholar57. Irusen E, Matthews JG, Takahashi A, Barnes PJ, Chung KF, Adcock IM. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol. 2002;109:649-57. [PMID: 11941315] CrossrefMedlineGoogle Scholar58. Hamid QA, Wenzel SE, Hauk PJ, Tsicopoulos A, Wallaert B, Lafitte JJ, . Increased glucocorticoid receptor in airway cells of glucocorticoid-insensitive asthma. Am J Respir Crit Care Med. 1999;159:1600-4. [PMID: 10228133] CrossrefMedlineGoogle Scholar59. Gagliardo R, Chanez P, Vignola AM, Bousquet J, Vachier I, Godard P, . Glucocorticoid receptor and in glucocorticoid dependent asthma. Am J Respir Crit Care Med. 2000;162:7-13. [PMID: 10903212] CrossrefMedlineGoogle Scholar60. Corrigan CJ, Brown PH, Barnes NC, Szefler SJ, Tsai JJ, Frew AJ, . Glucocorticoid resistance in chronic asthma. Glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics, and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro. Am Rev Respir Dis. 1991;144:1016-25. [PMID: 1952426] CrossrefMedlineGoogle Scholar61. Adcock IM, Lane SJ, Brown CR, Lee TH, Barnes PJ. Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma. J Exp Med. 1995;182:1951-8. [PMID: 7500041] CrossrefMedlineGoogle Scholar62. Matthews JG, Ito K, Barnes PJ, Adcock IM. Corticosteroid-resistant and corticosteroid-dependent asthma: two clinical phenotypes can be associated with the same in vitro defects in nuclear translocation and acetylation of histone 4 [Abstract]. Am J Respir Crit Care Med. 2000;161:A189. Google Scholar63. Keatings VM, Jatakanon A, Worsdell YM, Barnes PJ. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997;155:542-8. [PMID: 9032192] CrossrefMedlineGoogle Scholar64. Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:1635-9. [PMID: 10556133] CrossrefMedlineGoogle Scholar65. Nightingale JA, Rogers DF, Fan Chung K, Barnes PJ. No effect of inhaled budesonide on the response to inhaled ozone in normal subjects. Am J Respir Crit Care Med. 2000;161:479-86. [PMID: 10673189] CrossrefMedlineGoogle Scholar66. Culpitt SV, Rogers DF, Shah P, De Matos C, Russell RE, Donnelly LE, . Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:24-31. [PMID: 12406856] CrossrefMedlineGoogle Scholar67. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J. 2001;15:1110-2. [PMID: 11292684] CrossrefMedlineGoogle Scholar68. Ito K, Watanabe S, Kharitonov S, Hanazawa T, Adcock IM, Barnes PJ. Histone deacetylase activity and gene expression in COPD patients [Abstract]. Eur Respir J. 2001;18:316S. MedlineGoogle Scholar69. Montuschi P, Collins JV, Ciabattoni G, Lazzeri N, Corradi M, Kharitonov SA, . Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000;162:1175-7. [PMID: 10988150] CrossrefMedlineGoogle Scholar70. Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids. New developments. Am J Respir Crit Care Med. 1998;157:S1-53. [PMID: 9520807] CrossrefMedlineGoogle Scholar71. Heck S, Kullmann M, Gast A, Ponta H, Rahmsdorf HJ, Herrlich P, . A distinct modulating domain in glucocorticoid receptor monomers in the repression of activity of the transcription factor AP-1. EMBO J. 1994;13:4087-95. [PMID: 8076604] CrossrefMedlineGoogle Scholar72. Adcock IM, Nasuhara Y, Stevens DA, Barnes PJ. Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-B and lack of I-B involvement. Br J Pharmacol. 1999;127:1003-11. [PMID: 10433509] CrossrefMedlineGoogle Scholar73. Vayssiere BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, . Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol. 1997;11:1245-55. [PMID: 9259316] CrossrefMedlineGoogle Scholar74. Belvisi MG, Wicks SL, Battram CH, Bottoms SE, Redford JE, Woodman P, . Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity. J Immunol. 2001;166:1975-82. [PMID: 11160246] CrossrefMedlineGoogle Scholar75. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, . Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell. 2002;110:93-105. [PMID: 12151000] CrossrefMedlineGoogle Scholar76. Barnes PJ. New treatments for COPD. Nat Rev Drug Discov. 2002;1:437-46. [PMID: 12119745] CrossrefMedlineGoogle Scholar77. Ito K, Lim S, Chung KF, Barnes PJ, Adcock IM. Theophylline enhances histone deacetylase activity and restores glucocorticoid function during oxidative stress [Abstract]. Am J Respir Crit Care Med. 2002;165:A625. Google Scholar Author, Article, and Disclosure InformationAffiliations: From National Heart and Lung Institute, Imperial College, London, United Kingdom. Disclosures:Grants received: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca); Grants pending: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca).Corresponding Author: P.J. Barnes, DM, DSc, Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom; e-mail, p.j.[email protected]ac.uk. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNanotechnology based advanced therapeutic strategies for targeting interleukins in chronic respiratory diseasesLipopolysaccharide Regulates Pro- and Anti-Inflammatory Cytokines, Corticosterone, and Melatonin in ToadsThe central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to interventionAsthma and COVID-19: Emphasis on Adequate of as of and as a Effect of the resistance in asthma: and molecular effects of on a of allergic between and and gene expression of glucocorticoid and receptors from the for of human respiratory with glucocorticoids in the treatment of asthma: of the oral corticosteroids and persistent in from the asthma to bronchial asthma as for A of of Melatonin and Glucocorticoid with in the a between Melatonin and of in Steroid Drug by of proteins during the Efficacy of to in a of corticosteroids in asthma: the between and the novel mode of action of the Association and 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Annals of Internal Medicine · review · 370 citationsread the source →

Association between breastfeeding and intelligence, educational attainment, and income at 30 years of age: a prospective birth cohort study from Brazil.

Background: Breastfeeding has clear short-term benefits, but its long-term consequences on human capital are yet to be established. We aimed to assess whether breastfeeding duration was associated with intelligence quotient (IQ), years of schooling, and income at the age of 30 years, in a setting where no strong social patterning of breastfeeding exists. Methods: A prospective, population-based birth cohort study of neonates was launched in 1982 in Pelotas, Brazil. Information about breastfeeding was recorded in early childhood. At 30 years of age, we studied the IQ (Wechsler Adult Intelligence Scale, 3rd version), educational attainment, and income of the participants. For the analyses, we used multiple linear regression with adjustment for ten confounding variables and the G-formula. Findings: From June 4, 2012, to Feb 28, 2013, of the 5914 neonates enrolled, information about IQ and breastfeeding duration was available for 3493 participants. In the crude and adjusted analyses, the durations of total breastfeeding and predominant breastfeeding (breastfeeding as the main form of nutrition with some other foods) were positively associated with IQ, educational attainment, and income. We identified dose-response associations with breastfeeding duration for IQ and educational attainment. In the confounder-adjusted analysis, participants who were breastfed for 12 months or more had higher IQ scores (difference of 3·76 points, 95% CI 2·20-5·33), more years of education (0·91 years, 0·42-1·40), and higher monthly incomes (341·0 Brazilian reals, 93·8-588·3) than did those who were breastfed for less than 1 month. The results of our mediation analysis suggested that IQ was responsible for 72% of the effect on income. Interpretation: Breastfeeding is associated with improved performance in intelligence tests 30 years later, and might have an important effect in real life, by increasing educational attainment and income in adulthood. Funding: Wellcome Trust, International Development Research Center (Canada), CNPq, FAPERGS, and the Brazilian Ministry of Health.

The Lancet. Global health · 382 citationsread the source →

Insomnia disorder subtypes derived from life history and traits of affect and personality.

Background: Insomnia disorder is the second most prevalent mental disorder, and it is a primary risk factor for depression. Inconsistent clinical and biomarker findings in patients with insomnia disorder suggest that heterogeneity exists and that subtypes of this disease remain unrecognised. Previous top-down proposed subtypes in nosologies have had insufficient validity. In this large-scale study, we aimed to reveal robust subtypes of insomnia disorder by use of data-driven analyses on a multidimensional set of biologically based traits. Methods: In this series of studies, we recruited participants from the Netherlands Sleep Registry, a database of volunteers aged 18 years or older, who we followed up online to survey traits, sleep, life events, and health history with 34 selected questionnaires of which participants completed at least one. We identified insomnia disorder subtypes by use of latent class analyses. We evaluated the value of our identified subtypes of insomnia disorder by use of a second, non-overlapping cohort who were recruited through a newsletter that was emailed to a new sample of Netherlands Sleep Registry participants, and by assessment of within-subject stability over several years of follow-up. We extensively tested the clinical validity of these subtypes for the development of sleep complaints, comorbidities (including depression), and response to benzodiazepines; in two subtypes of insomnia disorder, we also assessed the clinical relevance of these subtypes by use of an electroencephalogram biomarker and the effectiveness of cognitive behavioural therapy. To facilitate implementation, we subsequently constructed a concise subtype questionnaire and we validated this questionnaire in the second, non-overlapping cohort. Findings: 4322 Netherlands Sleep Registry participants completed at least one of the selected questionnaires, a demographic questionnaire, and an assessment of their Insomnia Severity Index (ISI) between March 2, 2010, and Oct 28, 2016. 2224 (51%) participants had probable insomnia disorder, defined as an ISI score of at least 10, and 2098 (49%) participants with a lower ISI score served as a control group. With a latent class analysis of the questionnaire responses of 2224 participants, we identified five novel insomnia disorder subtypes: highly distressed, moderately distressed but reward sensitive (ie, with intact responses to pleasurable emotions), moderately distressed and reward insensitive, slightly distressed with high reactivity (to their environment and life events), and slightly distressed with low reactivity. In a second, non-overlapping replication sample of 251 new participants who were assessed between June 12, 2017, and Nov 26, 2017, five subtypes were also identified to be optimal. In both the development sample and replication sample, each participant was classified as having only one subtype with high posterior probability (0·91-1·00). In 215 of the original sample of 2224 participants with insomnia who were reassessed 4·8 (SD 1·6) years later (between April 13, 2017, and June 21, 2017), the probability of maintaining their original subtype was 0·87, indicating a high stability of the classification. We found differences between the identified subtypes in developmental trajectories, response to treatment, the presence of an electroencephalogram biomarker, and the risk of depression that was up to five times different between groups, which indicated a clinical relevance of these subtypes. Interpretation: High-dimensional data-driven subtyping of people with insomnia has addressed an unmet need to reduce the heterogeneity of insomnia disorder. Subtyping facilitates identification of the underlying causes of insomnia, development of personalised treatments, and selection of patients with the highest risk of depression for inclusion in trials regarding prevention of depression. Funding: European Research Council and Netherlands Organization for Scientific Research.

The lancet. Psychiatry · 143 citationsread the source →

Parental Adjustment following Pediatric Burn Injury: The Role of Guilt, Shame, and Self-Compassion.

Objective: The purpose of this study was to examine the association between factors: guilt, shame, self-compassion, and parents' psychological adjustment to their child's burn injury. Methods: Participants were 91 parents and primary caregivers (63 mothers, 25 fathers, 3 other) of 71 children recruited on the ward or at outpatient clinics during the first 8 weeks following their child's burn injury. In 20 cases, both parents participated, while for 51 children only one parent participated. Participants completed questionnaires which assessed adjustment (symptoms of depression, anxiety, and posttraumatic stress syndrome [PTSS]) as well as guilt, shame, and self-compassion. Results: Multilevel analysis indicated that feelings of guilt and shame were associated with poorer adjustment in parents, while parents who rated high in self-compassion reported fewer symptoms of depression and PTSS. Guilt and shame showed a differing pattern of effects with shame explaining more variance for anxiety and depression. Length of hospitalization predicted PTSS; however, the remaining injury factors (size of burn, requiring a skin graft) were unrelated to parental adjustment. Conclusions: Health-care professionals should pay close attention to families' subjective injury experiences. Screening for psychological distress should be offered to all families regardless of the size and severity of the burn injury.

Journal of pediatric psychology · 39 citationsread the source →

Psychometric evaluation of the Epilepsy-related Fears in Parents Questionnaire.

Objective: The aim of the article was to examine the psychometric properties of the Epilepsy-related Fears in Parents Questionnaire (EFPQ). Method: Internal consistency, factor structure, and construct validity were analyzed based on data from 291 parents participating in the baseline assessment of a quasi-experimental study on the efficacy of the FAMOSES (modulares Schulungsprogramm Epilepsie für Familien) parents' program. The control group of this study was used to calculate the test-retest reliability, while the responsiveness of the questionnaire was evaluated by comparing matched groups of FAMOSES participants and control parents. Results: An exploratory factor analysis revealed two factors of epilepsy-related fears, "Fears about short-term consequences of the child's epilepsy" (8 items) and "Fears about the future development of the child and the child's epilepsy" (9 items). Both showed good reliability (Cronbach's α=.89 and .91, resp.; test-retest reliability: ICC=.77 and .80, resp.), and construct validity was confirmed by correlations with epilepsy-related variables and psychosocial outcomes, e.g., with the Impact on Family Scale (r=.48 and .61, resp.). The FAMOSES parents' program significantly reduced epilepsy-related fears (p<.05 for both subscales). Conclusion: The EFPQ proved to be a reliable, valid, and responsive instrument for the assessment of parental fears about their child's epilepsy and can be recommended for use in future studies.

Epilepsy & behavior : E&B · 4 citationsread the source →

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

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

The Lancet. Neurology · 5441 citationsread the source →

Psychosocial Adjustment in Emerging Adults With and Without Spina Bifida: A 14-Year Follow-up Study.

Objective: A 14-year follow-up of youth with spina bifida (SB), as compared to a matched comparison sample without a chronic health condition, focused on psychosocial adjustment during emerging adulthood (ages 22-23). Methods: The initial cohort at time 1 consisted of 68 families with an 8-year-old or 9-year-old child with SB and a matched comparison sample of 68 typically developing children and their families. At the final assessment (time 7), participants included 56 emerging adults with SB (82% of those who participated at time 1) and 62 comparison youth (91% of those who participated at time 1) who completed a set of self-report measures. Results: Emerging adults with SB continue to lag behind across several important developmental milestones, including decision-making responsibility, involvement in social and romantic relationships, sexual intimacy, educational and vocational achievement, financial independence, and engagement in health-related behaviors. However, from a resilience perspective, these individuals also exhibited a number of strengths across the following areas: identity development, quality of social supports, and fewer problem behaviors (e.g., alcohol and other substance use). Most findings were still significant after controlling for a verbal intelligence quotient proxy. Conclusion: This study highlighted vulnerabilities and strengths of individuals with SB as they enter emerging adulthood, with considerable continuity across childhood, adolescence, and emerging adulthood.

Journal of developmental and behavioral pediatrics : JDBP · 6 citationsread the source →

Prevalence and identification of anxiety disorders in pregnancy: the diagnostic accuracy of the two-item Generalised Anxiety Disorder scale (GAD-2).

Objective: To estimate the population prevalence of anxiety disorders during pregnancy and investigate the diagnostic accuracy of the two-item Generalised Anxiety Disorder scale (GAD-2) for a) GAD and b) any anxiety disorder. Design: Cross-sectional survey using a stratified sampling design. Sampling weights were used in the analysis to adjust for the bias introduced by the stratified sampling. Setting: Inner-city maternity service, South London. Participants: 545 pregnant women were interviewed after their first antenatal appointment; 528 provided answers on the GAD-2 questions. Main outcome measures: Diagnosis generated by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (SCID). Results: Population prevalence of anxiety disorders was 17% (95% CI 12% to 21%): 5% (95% CI 3% to 6%) for GAD, 4% (95% CI 2% to 6%) for social phobia, 8% (95% CI 5% to 11%) for specific phobia and 2% (95% CI 1% to 4%) for obsessive-compulsive disorder. Post-traumatic stress disorder (PTSD) prevalence was unclear due to higher levels of reluctance to respond to PTSD interview questions but sensitivity analyses suggest population prevalence maybe up to 4% (95% CI 2% to 6%). Weighted sensitivity of GAD-2 for GAD (cut-off ≥3) was 69%, specificity 91%, positive predictive value 26%, negative predictive value 98% and likelihood ratio 7.35. For any anxiety disorder the weighted sensitivity was 26%, specificity 91%, positive predictive value 36%, negative predictive value 87% and likelihood ratio 2.92. Conclusions: Anxiety disorders are common but GAD-2 generates many false positives and may therefore be unhelpful in maternity services.

BMJ open · 50 citationsread the source →

A Latent Variable Approach to Differentiating Neural Mechanisms of Irritability and Anxiety in Youth.

Importance: Comorbidity is ubiquitous in psychiatry, but it is unclear how to differentiate neural mechanisms of co-occurring symptoms. Pediatric irritability and anxiety symptoms are prevalent and frequently co-occur. Threat orienting is pertinent to both phenotypes and is an ideal context in which to examine their unique and common neural mechanisms. Objectives: To decompose the unique and shared variances of pediatric irritability and anxiety symptoms and to determine neural correlates of these differentiated phenotypes during threat orienting. Design, setting, and participants: This investigation was a cross-sectional functional magnetic resonance imaging study. The setting was a research clinic at the National Institute of Mental Health. Participants were youth aged 8 to 18 years spanning multiple diagnostic categories (141 youth with disruptive mood dysregulation disorder, anxiety disorder, and/or attention-deficit/hyperactivity disorder and 56 healthy youth). This combination provided wide variation in levels of irritability and anxiety symptoms. Data were acquired between June 30, 2012, and June 28, 2016. Main outcomes and measures: Participants and parents rated youth's irritability on the Affective Reactivity Index and anxiety on the Screen for Child Anxiety Related Emotional Disorders. Bifactor analysis decomposed the unique and shared variances. A functional magnetic resonance imaging dot-probe task assessed attention orienting to angry (ie, threat) vs neutral faces. Whole-brain analyses examined associations between the bifactor-derived phenotypes and both neural activity and amygdala functional connectivity. Results: Among 197 participants included in the final analysis, the mean (SD) age was 13.1 (2.7) years, and 91 (46.2%) were female. The best-fit bifactor model (Comparative Fit Index, 0.959; Root Mean Square Error of Approximation, 0.066) included unique factors of parent-reported irritability, youth-reported irritability, and anxiety, as well as a common factor of negative affectivity. When the task required attention away from threat, higher parent-reported irritability was associated with increased activity in the insula, caudate, dorsolateral and ventrolateral prefrontal cortex, and inferior parietal lobule (t189≥4.15 for all, P < .001 for all). In contrast, higher anxiety was associated with decreased amygdala connectivity to the cingulate, thalamus, and precentral gyrus (t189≤-4.19 for all, P < .001 for all). These distinctive neural correlates did not emerge using a diagnostic approach. Conclusions and relevance: A latent variable approach to parsing co-occurring symptom dimensions revealed a novel double dissociation. During orientation away from threat, only irritability was associated with neural activity, whereas only anxiety was associated with amygdala connectivity. Despite the challenges of symptom co-occurrence for clinical neuroscience, data-driven phenotyping may facilitate a path forward.

JAMA psychiatry · 97 citationsread the source →

Adverse event profile and associated factors following surgical voluntary medical male circumcision in two regions of Namibia, 2015-2018.

Introduction: Monitoring clinical safety of voluntary medical male circumcision (VMMC) is critical to minimize risk as VMMC programs for HIV prevention are scaled. This cross-sectional analysis describes the adverse event (AE) profile of a large-scale, routine VMMC program and identifies factors associated with the development, severity, and timing of AEs to provide recommendations for program quality improvement. Materials and methods: From 2015-2018 there were 28,990 circumcisions performed in International Training and Education Center for Health (I-TECH) supported regions of Namibia in collaboration with the Ministry of Health and Social Services. Two routine follow-up visits after VMMC were scheduled to identify clients with AEs. Summary statistics were used to describe characteristics of all VMMC clients and the subset who experienced an AE. We used chi-square tests to evaluate associations between AE timing, patient age, and other patient and AE characteristics. We used a logistic regression model to explore associations between patient characteristics and AE severity. Results: Of the 498 clients with AEs (AE rate of 1.7%), 40 (8%) occurred ≤2 days, 262 (53%) occurred 3-7 days, 161 (32%) between day 8 and 14, and 35 (7%) were ≥15 days post-VMMC. Early AEs (on or before day 2) tended to be severe and categorized as bleeding, while infections were the most common AEs occurring later (p<0.001). Younger clients (aged 10-14 years) experienced more infections, whereas older clients experienced more bleeding (p<0.001). Conclusions: Almost 40% of AEs occurred after the second follow-up visit, of which 179 (91%) were infections. Improvements in pre-surgical and post-surgical counselling and post-operative educational materials encouraging clients to seek care at any time, adoption of alternative follow-up methods, and the addition of a third follow-up visit may improve outcomes for patients. Enhancing post-surgical counselling and emphasizing wound care for younger VMMC clients and their caregivers could help mitigate elevated risk of infection.

PloS one · 10 citationsread the source →

Preferences for dietary oils and fats in cooking and food preparation methods: a cross-sectional analysis of Australian adults.

Dietary oils and fats contain different fatty acid compositions that are associated with cardiometabolic disease risk. Despite their influence on disease outcomes, the types of dietary oils and fats predominately used in Australian households remain unknown. The aim of this study was to investigate the use of dietary oils and fats in cooking and food preparation in Australia. Adults living in Australia completed a cross-sectional online survey outlining their current household oil and fat use from July to December 2021. The survey was disseminated via social media platforms and included questions about the types of dietary oils and fats used for different cooking methods and the perceived motivators for choosing the main household oil. A total of 1248 participants responded to the survey. Participants were mostly female (91·6 %) aged between 25 and 44 years (56·7 %). The majority of participants (84·5 %) reported using some form of olive oil as their main source of oil for cooking and food preparation. Almost two-thirds of the sample (65·4 %) reported using extra virgin olive oil (EVOO), mainly in raw food preparation (71·5 %) or savoury baking and roasting (58 %). Fewer households reported using rice bran oil (4·6 %), canola oil (4·3 %) and vegetable oil (1·8 %). Almost half of all participants (49·6 %) identified perceived health benefits as the primary motivating factor for their main choice of oil, followed by sensory preference (46·7 %), versatility (10·2 %) and convenience (8·8 %). Australian adults frequently use olive oil, specifically EVOO, as the main oil for cooking and food preparation in the household.

The British journal of nutrition · 4 citationsread the source →

Vulnerability to extreme heat by socio-demographic characteristics and area green space among the elderly in Michigan, 1990-2007.

Objectives: We examined how individual and area socio-demographic characteristics independently modified the extreme heat (EH)-mortality association among elderly residents of 8 Michigan cities, May-September, 1990-2007. Methods: In a time-stratified case-crossover design, we regressed cause-specific mortality against EH (indicator for 4-day mean, minimum, maximum or apparent temperature above 97th or 99 th percentiles). We examined effect modification with interactions between EH and personal marital status, age, race, sex and education and ZIP-code percent "non-green space" (National Land Cover Dataset), age, race, income, education, living alone, and housing age (U.S. Census). Results: In models including multiple effect modifiers, the odds of cardiovascular mortality during EH (99 th percentile threshold) vs. non-EH were higher among non-married individuals (1.21, 95% CI=1.14-1.28 vs. 0.98, 95% CI=0.90-1.07 among married individuals) and individuals in ZIP codes with high (91%) non-green space (1.17, 95% CI=1.06-1.29 vs. 0.98, 95% CI=0.89-1.07 among individuals in ZIP codes with low (39%) non-green space). Results suggested that housing age may also be an effect modifier. For the EH-respiratory mortality association, the results were inconsistent between temperature metrics and percentile thresholds of EH but largely insignificant. Conclusions: Green space, housing and social isolation may independently enhance elderly peoples' heat-related cardiovascular mortality vulnerability. Local adaptation efforts should target areas and populations at greater risk.

Environmental research · 84 citationsread the source →

Peer-to-peer support model to improve quality of life among highly vulnerable, low-income older adults in Cape Town, South Africa.

Background: Developing countries are experiencing rapid population ageing. Many do not have the resources or formal structures available to support the health and wellbeing of people as they age. In other contexts, the use of peer support programmes have shown favourable outcomes in terms of reducing loneliness, increasing physical activity and managing chronic disease. Such programmes have not been previously developed or tested in African countries. We piloted a peer-to-peer support model among vulnerable community-dwelling adults in a developing country (South Africa) to examine the program's effect on wellbeing and social engagement. Methods: A pre-post, pilot design was used to evaluate targeted outcomes, including wellbeing, social support, social interaction, mood, loneliness and physical activity. A total of 212 persons, aged 60+ years and living independently in a low-income area in Cape Town were recruited and screened for eligibility by trained assessors. Participants were assessed using the interRAI CheckUp, WHO-5 Wellbeing index, and the MOS-SS 8 instruments before and after the 5-month intervention, during which they received regular visits and phone calls from trained peer volunteers. During visits volunteers administered a wellness screening, made referrals to health and social services; built friendships with clients; encouraged social engagement; promoted healthy living; and provided emotional and informational support. Results: Volunteer visits with clients significantly increased levels of self-reported wellbeing by 58%; improved emotional and informational support by 50%; decreased reports of reduced social interaction by 91%; reduced loneliness by 70%; improved mood scores represented as anxiety, depression, lack of interest or pleasure in activities, and withdrawal from activities of interest; and increased levels of physical activity from 49 to 66%. Discussion: The intervention led to demonstrable improvement in client wellbeing. Policymakers should consider integrating peer-support models into existing health programs to better address the needs of the elderly population and promote healthy ageing in resource-poor community settings. Longer-term and more rigorous studies with a control group are needed to support these findings and to investigate the potential impact of such interventions on health outcomes longitudinally.

BMC geriatrics · 37 citationsread the source →

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

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

EClinicalMedicine · 59 citationsread the source →

Uterine allotransplantation in ewes using an aortocava patch.

Background: We investigated a novel allotransplantation model using an aortocava patch in ewes. Methods and results: We carried out 10 uterine orthotopic allotransplantations in ewes with end-to-side anastomosis of the aortocava donor patch on the left external iliac vessel recipient. The immunosuppressive protocol was a combination of cyclosporine (10 mg/kg/day) and mycophenolic acid (3 g/day). An estimation of the immunosuppressive therapy exposure was performed by measuring the area under the curve (AUC) of immunosuppressive plasma concentrations. The graft was assessed by vaginoscopy, magnetic resonance imaging (MRI) and second look laparotomy at 6, 8 and 10 weeks, respectively. The median (range) times for cold and warm ischemia were 95 min (75-130) and 91 min (55-165), respectively. All the vascular anastomoses were patent at the end of the surgery. The median AUC of cyclosporine and mycophenolic acid were 1.24 mg h/l (0.34-3.85) and 18.40 mg h/l (3.76-42.35), respectively. Of the 10 ewes receiving a transplant, 6 could be assessed. Cervical biopsies showed signs of necrosis in all six ewes. The MRI results correlated with the macroscopic observations of the 'second look' laparotomy. The aortocava vascular pedicles were thrombosed, adding to the peripheral neovascularization. Graft histology showed endometrial tissue in two out of six ewes. Conclusions: Mobility of the transplant within the pelvis, the length of the vascular pedicle and rejection can explain the high rate of transplant necrosis. The particular digestive anatomy and physiology of ruminants makes it difficult to administer an optimal immunosuppressive treatment. MRI appears to be a good non-invasive examination for graft estimation.

Human reproduction (Oxford, England) · 31 citationsread the source →

Spirituality, religiosity, and spiritual pain among caregivers of patients with advanced cancer.

Background: Caregivers of patients with advanced cancer often face physical, social, and emotional distress as well as spiritual pain. Limited research has focused on the spiritual aspects of caregivers' suffering in the palliative care setting. Methods: We interviewed 43 caregivers of patients with advanced cancer in our palliative care outpatient clinic. We determined demographic characteristics, religious affiliation, and relationship to the patient. Levels of spirituality, religiosity, and spiritual pain were self-reported using numeric rating scales (0 = lowest; 10 = highest). The participants completed various validated questionnaires to assess sleep disturbances, psychosocial distress, coping skills, and quality of life (QOL). Results: The median age was 52 years (range, 21-83); 29 (67%) were women, 34 (78%) were white, 7 (17%) were African American, and 2 (5%) were Hispanic; 39 (91%) were Christian, 1 (2%) was Jewish, and 1 (2%) was agnostic; 37 (86%) were married; 18 (42%) were working full time; and 25 (58%) were spouses. All considered themselves spiritual, and 98% considered themselves religious, with median scores of 8 (interquartile range, 6-10) and 8 (interquartile range, 4-9), respectively. All the caregivers reported that spirituality and religiosity helped them cope with their loved one's illness, and many reported that spirituality and religiosity had a positive impact on their loved one's physical (58%) and emotional (76%) symptoms. Spiritual pain was reported by 23 (58%), with a median score of 5 (interquartile range, 2-8). Caregivers with spiritual pain had higher levels of anxiety (median 10 vs 4; P = .002), depression (6 vs 2; P = .006), and denial (3 vs 2; P = .01); more behavioral disengagement (3 vs 2; P = 0.011) more dysfunctional coping strategies (19 vs 16; P < .001) and worse QOL (70 vs 51; P < .001) than those who did not have spiritual pain. Conclusions: The majority of caregivers of patients with advanced cancer considered themselves spiritual and religious. Despite this, there is high prevalence of spiritual pain in this population. Caregivers with spiritual pain experienced worse psychological distress and worse QOL. These findings support the importance of spiritual assessment of and spiritual support for caregivers in this setting.

The American journal of hospice & palliative care · 65 citationsread the source →

Cancer mortality in India: a nationally representative survey.

Background: The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the cause of death in 2001-03 in homes in small areas that were chosen to be representative of all the parts of India. Methods: At least 130 trained physicians independently assigned causes to 122,429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. Findings: 7137 of 122,429 study deaths were due to cancer, corresponding to 556,400 national cancer deaths in India in 2010. 395,400 (71%) cancer deaths occurred in people aged 30-69 years (200,100 men and 195,300 women). At 30-69 years, the three most common fatal cancers were oral (including lip and pharynx, 45,800 [22·9%]), stomach (25,200 [12·6%]), and lung (including trachea and larynx, 22,900 [11·4%]) in men, and cervical (33,400 [17·1%]), stomach (27,500 [14·1%]), and breast (19,900 [10·2%]) in women. Tobacco-related cancers represented 42·0% (84,000) of male and 18·3% (35,700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100,000 were similar in rural (men 95·6 [99% CI 89·6-101·7] and women 96·6 [90·7-102·6]) and urban areas (men 102·4 [92·7-112·1] and women 91·2 [81·9-100·5]), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 [97·4-115·7] vs most educated 45·7 [37·8-53·6]; women, illiterate 106·7 [99·9-113·6] vs most educated 43·4 [30·7-56·1]). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 [0·64-0·71] vs 340, 1·06 [1·05-1·08]). Interpretation: Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. Funding: Bill & Melinda Gates Foundation and US National Institutes of Health.

Lancet (London, England) · 296 citationsread the source →

An 8-year longitudinal study of the natural history of threshold, subthreshold, and partial eating disorders from a community sample of adolescents.

The authors examined the natural history of threshold, subthreshold, and partial eating disorders in a community sample of 496 adolescent girls who completed annual diagnostic interviews over an 8-year period. Lifetime prevalence by age 20 years was 0.6% and 0.6% for threshold and subthreshold anorexia nervosa (AN), 1.6% and 6.1% for threshold and subthreshold bulimia nervosa (BN), 1.0% and 4.6% for threshold and subthreshold binge-eating disorder (BED), and 4.4% for purging disorder (PD). Overall, 12% of adolescents experienced some form of eating disorder. Subthreshold BN and BED and threshold PD were associated with elevated treatment, impairment, and distress. Peak age of onset was 17-18 years for BN and BED and 18-20 years for PD. Average episode duration in months was 3.9 for BN and BED and 5.1 for PD. One-year recovery rates ranged from 91% to 96%. Relapse rates were 41% for BN, 33% for BED, and 5% for PD. For BN and BED, subthreshold cases often progressed to threshold cases and diagnostic crossover was most likely for these disorders. Results suggest that subthreshold eating disorders are more prevalent than threshold eating disorders and are associated with marked impairment.

Journal of abnormal psychology · 232 citationsread the source →

A national profile of childhood epilepsy and seizure disorder.

Objective: To determine sociodemographics, patterns of comorbidity, and function of US children with reported epilepsy/seizure disorder. Methods: Bivariate and multivariable cross-sectional analysis of data from the National Survey of Children's Health (2007) on 91 605 children ages birth to 17 years, including 977 children reported by their parents to have been diagnosed with epilepsy/seizure disorder. Results: Estimated lifetime prevalence of epilepsy/seizure disorder was 10.2/1000 (95% confidence interval [CI]: 8.7-11.8) or 1%, and of current reported epilepsy/seizure disorder was 6.3/1000 (95% CI: 4.9-7.8). Epilepsy/seizure disorder prevalence was higher in lower-income families and in older, male children. Children with current reported epilepsy/seizure disorder were significantly more likely than those never diagnosed to experience depression (8% vs 2%), anxiety (17% vs 3%), attention-deficit/hyperactivity disorder (23% vs 6%), conduct problems (16% vs 3%), developmental delay (51% vs 3%), autism/autism spectrum disorder (16% vs 1%), and headaches (14% vs 5%) (all P < .05). They had greater risk of limitation in ability to do things (relative risk: 9.22; 95% CI: 7.56-11.24), repeating a school grade (relative risk: 2.59; CI: 1.52-4.40), poorer social competence and greater parent aggravation, and were at increased risk of having unmet medical and mental health needs. Children with prior but not current seizures largely had intermediate risk. Conclusions: In a nationally representative sample, children with seizures were at increased risk for mental health, developmental, and physical comorbidities, increasing needs for care coordination and specialized services. Children with reported prior but not current seizures need further study to establish reasons for their higher than expected levels of reported functional limitations.

Pediatrics · 386 citationsread the source →

Functional connectivity magnetic resonance imaging classification of autism.

Group differences in resting state functional magnetic resonance imaging connectivity between individuals with autism and typically developing controls have been widely replicated for a small number of discrete brain regions, yet the whole-brain distribution of connectivity abnormalities in autism is not well characterized. It is also unclear whether functional connectivity is sufficiently robust to be used as a diagnostic or prognostic metric in individual patients with autism. We obtained pairwise functional connectivity measurements from a lattice of 7266 regions of interest covering the entire grey matter (26.4 million connections) in a well-characterized set of 40 male adolescents and young adults with autism and 40 age-, sex- and IQ-matched typically developing subjects. A single resting state blood oxygen level-dependent scan of 8 min was used for the classification in each subject. A leave-one-out classifier successfully distinguished autism from control subjects with 83% sensitivity and 75% specificity for a total accuracy of 79% (P = 1.1 × 10(-7)). In subjects <20 years of age, the classifier performed at 89% accuracy (P = 5.4 × 10(-7)). In a replication dataset consisting of 21 individuals from six families with both affected and unaffected siblings, the classifier performed at 71% accuracy (91% accuracy for subjects <20 years of age). Classification scores in subjects with autism were significantly correlated with the Social Responsiveness Scale (P = 0.05), verbal IQ (P = 0.02) and the Autism Diagnostic Observation Schedule-Generic's combined social and communication subscores (P = 0.05). An analysis of informative connections demonstrated that region of interest pairs with strongest correlation values were most abnormal in autism. Negatively correlated region of interest pairs showed higher correlation in autism (less anticorrelation), possibly representing weaker inhibitory connections, particularly for long connections (Euclidean distance >10 cm). Brain regions showing greatest differences included regions of the default mode network, superior parietal lobule, fusiform gyrus and anterior insula. Overall, classification accuracy was better for younger subjects, with differences between autism and control subjects diminishing after 19 years of age. Classification scores of unaffected siblings of individuals with autism were more similar to those of the control subjects than to those of the subjects with autism. These findings indicate feasibility of a functional connectivity magnetic resonance imaging diagnostic assay for autism.

Brain : a journal of neurology · 284 citationsread the source →