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Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

Background: Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. Methods: We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Findings: Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroconversion to type 1 poliovirus were 166 (98·8%) of 168, 95% CI 95·8-99·7; 178 (100%), 97·9-100·0; and 175 (100%), 97·9-100·0. Proportions with seroconvsion to type 3 poliovirus were 163 (98·2%) of 166, 94·8-99·4; 177 (100%), 97·9-100·0, and 172 (98·9%) of 174, 95·9-99·7. Non-inferiority was thus shown for the bOPV-containing schedules compared with the all-IPV schedule, with no significant differences between groups. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroprotective antibody titres to type 1 poliovirus were 168 (98·8%) of 170, 95% CI 95·8-99·7; 181 (100%), 97·9-100·0; and 177 (100%), 97·9-100·0. Proportions to type 3 poliovirus were 166 (98·2%) of 169, 94·9-99·4; 180 (100%), 97·9-100·0; and 174 (98·9%) of 176, 96·0-99·7. Non-inferiority comparisons could not be done for this outcome because median titres for the groups receiving OPV were greater than the assay's upper limit of detection (log2 titres >10·5). The proportions of children seroconverting to type 2 poliovirus in the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, were 130 (77·4%) of 168, 95% CI 70·5-83·0; 169 (96·0%) of 176, 92·0-98·0; and 175 (100%), 97·8-100. IPV-bOPV schedules resulted in almost a 0·3 log reduction of type 2 faecal shedding compared with the IPV-only schedule. No participants died during the trial; 81 serious adverse events were reported, of which one was thought to be possibly vaccine-related (intestinal intussusception). Interpretation: Seroconversion rates against polioviruses types 1 and 3 were non-inferior in sequential schedules containing IPV and bOPV, compared with an all-IPV schedule, and proportions of infants with protective antibodies were high after all three schedules. One or two doses of bOPV after IPV boosted intestinal immunity for poliovirus type 2, suggesting possible cross protection. Additionally, there was evidence of humoral priming for type 2 from one dose of IPV. Our findings could give policy makers flexibility when choosing a vaccination schedule, especially when trying to eliminate vaccine-associated and vaccine-derived poliomyelitis. Funding: Bill & Melinda Gates Foundation.

The Lancet. Infectious diseases · randomised controlled trial · 60 citationsread the source →

Attrition in Conversational Agent-Delivered Mental Health Interventions: Systematic Review and Meta-Analysis.

Background: Conversational agents (CAs) or chatbots are computer programs that mimic human conversation. They have the potential to improve access to mental health interventions through automated, scalable, and personalized delivery of psychotherapeutic content. However, digital health interventions, including those delivered by CAs, often have high attrition rates. Identifying the factors associated with attrition is critical to improving future clinical trials. Objective: This review aims to estimate the overall and differential rates of attrition in CA-delivered mental health interventions (CA interventions), evaluate the impact of study design and intervention-related aspects on attrition, and describe study design features aimed at reducing or mitigating study attrition. Methods: We searched PubMed, Embase (Ovid), PsycINFO (Ovid), Cochrane Central Register of Controlled Trials, and Web of Science, and conducted a gray literature search on Google Scholar in June 2022. We included randomized controlled trials that compared CA interventions against control groups and excluded studies that lasted for 1 session only and used Wizard of Oz interventions. We also assessed the risk of bias in the included studies using the Cochrane Risk of Bias Tool 2.0. Random-effects proportional meta-analysis was applied to calculate the pooled dropout rates in the intervention groups. Random-effects meta-analysis was used to compare the attrition rate in the intervention groups with that in the control groups. We used a narrative review to summarize the findings. Results: The systematic search retrieved 4566 records from peer-reviewed databases and citation searches, of which 41 (0.90%) randomized controlled trials met the inclusion criteria. The meta-analytic overall attrition rate in the intervention group was 21.84% (95% CI 16.74%-27.36%; I2=94%). Short-term studies that lasted ≤8 weeks showed a lower attrition rate (18.05%, 95% CI 9.91%- 27.76%; I2=94.6%) than long-term studies that lasted >8 weeks (26.59%, 95% CI 20.09%-33.63%; I2=93.89%). Intervention group participants were more likely to attrit than control group participants for short-term (log odds ratio 1.22, 95% CI 0.99-1.50; I2=21.89%) and long-term studies (log odds ratio 1.33, 95% CI 1.08-1.65; I2=49.43%). Intervention-related characteristics associated with higher attrition include stand-alone CA interventions without human support, not having a symptom tracker feature, no visual representation of the CA, and comparing CA interventions with waitlist controls. No participant-level factor reliably predicted attrition. Conclusions: Our results indicated that approximately one-fifth of the participants will drop out from CA interventions in short-term studies. High heterogeneities made it difficult to generalize the findings. Our results suggested that future CA interventions should adopt a blended design with human support, use symptom tracking, compare CA intervention groups against active controls rather than waitlist controls, and include a visual representation of the CA to reduce the attrition rate. Trial registration: PROSPERO International Prospective Register of Systematic Reviews CRD42022341415; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022341415.

Journal of medical Internet research · meta-analysis · 31 citationsread the source →

Randomized controlled trial of a brief online self-compassion intervention for mothers of infants: Effects on mental health outcomes.

Objective: To test the effectiveness of a brief self-compassion intervention in improving mental health outcomes for mothers of infants. Method: A randomized controlled trial study design was used. A community sample of mothers of infants (<2 years) completed measures of self-compassion, fears of compassion, psychological flexibility, depression, anxiety, stress, symptoms of posttraumatic stress, and infant feeding experiences. Mothers randomized to intervention received access to online self-compassion resources, and 248 mothers (intervention n = 94, waitlist-control n = 154) completed postintervention assessment 8 weeks later. Results: Overall, 62.8% (n = 59) of intervention participants accessed the resources per-protocol, and lower fear of compassion scores predicted resource use. At postintervention, mothers who used the resources had improved scores for posttraumatic stress symptoms (95% confidence interval [CI] = 0.31-5.47, p = .028), depression (95% CI = 0.15-2.01, p = .023), self-compassionate action (95% CI = 0.41-3.45, p = .012), and engagement with compassion from others (95% CI = 0.22-5.49, p = .034) compared to waitlist-control. Fears of compassion moderated intervention effectiveness. There were no effects on other outcome variables. Conclusions: Findings support the potential effectiveness of interventions based on compassion-focused therapy to improve maternal mental health.

Journal of clinical psychology · randomised controlled trial · 22 citationsread the source →

Metabolic and bariatric surgery versus intensive non-surgical treatment for adolescents with severe obesity (AMOS2): a multicentre, randomised, controlled trial in Sweden.

Background: Severe obesity in adolescents has a profound impact on current and future health. Metabolic and bariatric surgery (MBS) is increasingly used in adolescents internationally. However, to our knowledge, there are no randomised trials examining the currently most used surgical techniques. Our aim was to evaluate changes in BMI and secondary health and safety outcomes after MBS. Methods: The Adolescent Morbid Obesity Surgery 2 (AMOS2) study is a randomised, open-label, multicentre trial done at three university hospitals in Sweden (located in Stockholm, Gothenburg, and Malmö). Adolescents aged 13-16 years with a BMI of at least 35 kg/m2, who had attended treatment for obesity for at least 1 year, passed assessments from a paediatric psychologist and a paediatrician, and had a Tanner pubertal stage of at least 3, were randomly assigned (1:1) to MBS or intensive non-surgical treatment. Exclusion criteria included monogenic or syndromic obesity, major psychiatric illness, and regular self-induced vomiting. Computerised randomisation was stratified for sex and recruitment site. Allocation was concealed for both staff and participants until the end of the inclusion day, and then all participants were unmasked to treatment intervention. One group underwent MBS (primarily gastric bypass), while the other group received intensive non-surgical treatment starting with 8 weeks of low-calorie diet. The primary outcome was 2-year change in BMI, analysed as intention-to-treat. The trial is registered at ClinicalTrials.gov, NCT02378259. Findings: 500 people were assessed for eligibility between Aug 27, 2014, and June 7, 2017. 450 participants were excluded (397 did not meet inclusion criteria, 39 declined to participate, and 14 were excluded for various other reasons). Of the 50 remaining participants, 25 (19 females and six males) were randomly assigned to receive MBS and 25 (18 females and seven males) were assigned to intensive non-surgical treatment. Three participants (6%; one in the MBS group and two in the intensive non-surgical treatment group) did not participate in the 2-year follow-up, and in total 47 (94%) participants were assessed for the primary endpoint. Mean age of participants was 15·8 years (SD 0·9) and mean BMI at baseline was 42·6 kg/m2 (SD 5·2). After 2 years, BMI change was -12·6 kg/m2 (-35·9 kg; n=24) among adolescents undergoing MBS (Roux-en-Y gastric bypass [n=23], sleeve gastrectomy [n=2]) and -0·2 kg/m2 (0·4 kg; [n=23]) among participants in the intensive non-surgical treatment group (mean difference -12·4 kg/m2 [95% CI -15·5 to -9·3]; p<0·0001). Five (20%) patients in the intensive non-surgical group crossed over to MBS during the second year. Adverse events (n=4) after MBS were mild but included one cholecystectomy. Regarding safety outcomes, surgical patients had a reduction in bone mineral density, while controls were unchanged after 2 years (z-score change mean difference -0·9 [95% CI -1·2 to -0·6]). There were no significant differences between the groups in vitamin and mineral levels, gastrointestinal symptoms (except less reflux in the surgical group), or in mental health at the 2-year follow-up. Interpretation: MBS is an effective and well tolerated treatment for adolescents with severe obesity resulting in substantial weight loss and improvements in several aspects of metabolic health and physical quality of life over 2 years, and should be considered in adolescents with severe obesity. Funding: Sweden's Innovation Agency, Swedish Research Council Health.

The Lancet. Child & adolescent health · randomised controlled trial · 45 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 →

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 →

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

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

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

Increasing Physical Activity Through Principles of Habit Formation in New Gym Members: a Randomized Controlled Trial

BACKGROUND: The promotion of physical activity (PA) is paramount to public health, yet interventions in the social cognitive tradition have yielded negligible improvements. The limited progression may be due to an overreliance on intention as the proximal determinant of behavior and a lack of consideration of implicit/automatic processes. The purpose of this study was to examine the impact of a habit formation intervention on PA over 8 weeks in a two-arm parallel design, randomized controlled trial. METHODS: Participants (n = 94) were new gym members with the intention to engage in PA but below international PA guidelines at baseline, who were randomized into a control or habit experimental group. The experimental group attended a workshop (at baseline) and received a follow-up booster phone call at week 4. The primary outcome of the study was minutes of moderate-vigorous intensity PA (MVPA) at week 8. The secondary outcome was a manipulation check to determine if the experimental group effectively incorporated habit-building constructs (cues and practice consistency). RESULTS: The experimental group showed a significant increase in MVPA after 8 weeks in both accelerometry (d = 0.39, p = .04) and self-report (d = 0.53, p = .01) compared with the control group. The experimental group also showed an increase in use of cues (d = 0.56, p < .001) and practice consistency (d = 0.40, p = .01) at week 8. CONCLUSION: The results contribute to the initial validity of increasing PA through a focus on preparation cues and practice consistency. Future research should replicate these findings and extend the duration of assessment to evaluate whether PA changes are sustained. Registered Trial Number NCT02785107.

Annals of Behavioral Medicine · randomised controlled trial · 101 citationsread the source →

Differential changes in functional disability and pain intensity over the course of psychological treatment for children with chronic pain.

Patients presenting for treatment of chronic pain often believe that pain reduction must be achieved before returning to normal functioning. However, treatment programs for chronic pain typically take a rehabilitative approach, emphasizing decreasing pain-related disability first with the expectation that pain reduction will follow. This information is routinely provided to patients, yet no studies have systematically examined the actual trajectories of pain and disability in a clinical care setting. In this study of youth with chronic pain (N=94, 8 to 18 years), it was hypothesized that 1) functional disability and pain would decrease over the course of psychological treatment for chronic pain and 2) functional disability would decrease more quickly than pain intensity. Participants received cognitive behavioral therapy (CBT) for pain management (M=5.6 sessions) plus standard medical care. The Functional Disability Inventory and a Numeric Rating Scale of average pain intensity were completed by the child at every CBT session. Hierarchical linear modeling was conducted to examine the longitudinal trajectories of disability and pain. Standardized estimates of the slopes of change were obtained to test differences in rates of change between pain and disability. Results showed an overall significant decline in functional disability over time. Although pain scores reduced slightly from pretreatment to posttreatment, the longitudinal decline over treatment was not statistically significant. As expected, the rate of change of disability was significantly more rapid than pain. Evidence for variability in treatment response was noted, suggesting the need for additional research into individual trajectories of change in pediatric pain treatment.

Pain · 82 citationsread the source →

The Use of Online Posts to Identify Barriers to and Facilitators of HIV Pre-exposure Prophylaxis (PrEP) Among Men Who Have Sex with Men: A Comparison to a Systematic Review of the Peer-Reviewed Literature.

Pre-exposure prophylaxis (PrEP) remains an under-utilized HIV prevention tool among men who have sex with men (MSM). To more comprehensively elucidate barriers and facilitators to PrEP use among US MSM, we conducted a systematic review of peer-reviewed published articles and content analysis of online posts about PrEP. We searched peer-reviewed databases (Medline, Web of Science, Google Scholar) using MESH headings and keywords about PrEP and/or HIV prevention from 2005 to 2015. We included original studies among MSM in the US that reported on barriers, facilitators, or other factors related to PrEP use. We also searched online posts and associated comments (news articles, opinion pieces, blogs and other social media posts) in diverse venues (Facebook, Slate Outward, Huffington Post Gay Voices, Queerty, and My PrEP Experience blog) to identify posts about PrEP. We used content analysis to identify themes and compare potential differences between the peer-reviewed literature and online posts. We identified 25 peer-reviewed articles and 28 online posts meeting inclusion criteria. We identified 48 unique barriers and 46 facilitators to using PrEP. These 94 themes fit into six overarching categories: (1) access (n = 14), (2) attitudes/beliefs (n = 24), (3) attributes of PrEP (n = 13), (4) behaviors (n = 11), (5) sociodemographic characteristics (n = 8), and (6) social network (n = 6). In all categories, analysis of online posts resulted in identification of a greater number of unique themes. Thirty-eight themes were identified in the online posts that were not identified in the peer-reviewed literature. We identified barriers and facilitators to PrEP in online posts that were not identified in a systematic review of the peer-reviewed literature. By incorporating data both from a systematic review of peer-reviewed articles and from online posts, we have identified salient and novel information about barriers to and facilitators of PrEP use. Traditional research approaches may not comprehensively capture current factors important for designing and implementing PrEP related interventions.

AIDS and behavior · systematic review · 68 citationsread the source →

Peer Support for the Hardly Reached: A Systematic Review.

Background: Health disparities are aggravated when prevention and care initiatives fail to reach those they are intended to help. Groups can be classified as hardly reached according to a variety of circumstances that fall into 3 domains: individual (e.g., psychological factors), demographic (e.g., socioeconomic status), and cultural-environmental (e.g., social network). Several reports have indicated that peer support is an effective means of reaching hardly reached individuals. However, no review has explored peer support effectiveness in relation to the circumstances associated with being hardly reached or across diverse health problems. Objectives: To conduct a systematic review assessing the reach and effectiveness of peer support among hardly reached individuals, as well as peer support strategies used. Search methods: Three systematic searches conducted in PubMed identified studies that evaluated peer support programs among hardly reached individuals. In aggregate, the searches covered articles published from 2000 to 2015. Selection criteria: Eligible interventions provided ongoing support for complex health behaviors, including prioritization of hardly reached populations, assistance in applying behavior change plans, and social-emotional support directed toward disease management or quality of life. Studies were excluded if they addressed temporally isolated behaviors, were limited to protocol group classes, included peer support as the dependent variable, did not include statistical tests of significance, or incorporated comparison conditions that provided appreciable social support. Data collection and analysis: We abstracted data regarding the primary health topic, categorizations of hardly reached groups, program reach, outcomes, and strategies employed. We conducted a 2-sample t test to determine whether reported strategies were related to reach. Results: Forty-seven studies met our inclusion criteria, and these studies represented each of the 3 domains of circumstances assessed (individual, demographic, and cultural-environmental). Interventions addressed 8 health areas, most commonly maternal and child health (25.5%), diabetes (17.0%), and other chronic diseases (14.9%). Thirty-six studies (76.6%) assessed program reach, which ranged from 24% to 79% of the study population. Forty-four studies (94%) reported significant changes favoring peer support. Eleven strategies emerged for engaging and retaining hardly reached individuals. Among them, programs that reported a strategy of trust and respect had higher participant retention (82.8%) than did programs not reporting such a strategy (48.1%; P = .003). In 5 of the 6 studies examining moderators of the effects of peer support, peer support benefits were greater among individuals characterized by disadvantage (e.g., low health literacy). Conclusions: Peer support is a broad and robust strategy for reaching groups that health services too often fail to engage. The wide range of audiences and health concerns among which peer support is successful suggests that a basis for its success may be its flexible response to different contexts, including the intended audience, health problems, and setting. Public health implications: The general benefits of peer support and findings suggesting that it may be more effective among those at heightened disadvantage indicate that peer support should be considered in programs intended to reach and benefit those too often hardly reached. Because engendering trust and respect was significantly associated with participant retention, programs should emphasize this strategy.

American journal of public health · systematic review · 148 citationsread the source →

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

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

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

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial.

Background: Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression. Methods: In this randomised, multicentre, non-inferiority clinical trial, we recruited patients who were referred to specialty neurostimulation centres based at three Canadian university hospitals (Centre for Addiction and Mental Health and Toronto Western Hospital, Toronto, ON, and University of British Columbia Hospital, Vancouver, BC). Participants were aged 18-65 years, were diagnosed with a current treatment-resistant major depressive episode or could not tolerate at least two antidepressants in the current episode, were receiving stable antidepressant medication doses for at least 4 weeks before baseline, and had an HRSD-17 score of at least 18. Participants were randomly allocated (1:1) to treatment groups (10 Hz rTMS or iTBS) by use of a random permuted block method, with stratification by site and number of adequate trials in which the antidepressants were unsuccessful. Treatment was delivered open-label but investigators and outcome assessors were masked to treatment groups. Participants were treated with 10 Hz rTMS or iTBS to the left dorsolateral prefrontal cortex, administered on 5 days a week for 4-6 weeks. The primary outcome measure was change in 17-item Hamilton Rating Scale for Depression (HRSD-17) score, with a non-inferiority margin of 2·25 points. For the primary outcome measure, we did a per-protocol analysis of all participants who were randomly allocated to groups and who attained the primary completion point of 4 weeks. This trial is registered with ClinicalTrials.gov, number NCT01887782. Findings: Between Sept 3, 2013, and Oct 3, 2016, we randomly allocated 205 participants to receive 10 Hz rTMS and 209 participants to receive iTBS. 192 (94%) participants in the 10 Hz rTMS group and 193 (92%) in the iTBS group were assessed for the primary outcome after 4-6 weeks of treatment. HRSD-17 scores improved from 23·5 (SD 4·4) to 13·4 (7·8) in the 10 Hz rTMS group and from 23·6 (4·3) to 13·4 (7·9) in the iTBS group (adjusted difference 0·103 [corrected], lower 95% CI -1·16; p=0·0011), which indicated non-inferiority of iTBS. Self-rated intensity of pain associated with treatment was greater in the iTBS group than in the 10 Hz rTMS group (mean score on verbal analogue scale 3·8 [SD 2·0] vs 3·4 [2·0] out of 10; p=0·011). Dropout rates did not differ between groups (10 Hz rTMS: 13 [6%] of 205 participants; iTBS: 16 [8%] of 209 participants); p=0·6004). The most common treatment-related adverse event was headache in both groups (10 Hz rTMS: 131 [64%] of 204; iTBS: 136 [65%] of 208). Interpretation: In patients with treatment-resistant depression, iTBS was non-inferior to 10 Hz rTMS for the treatment of depression. Both treatments had low numbers of dropouts and similar side-effects, safety, and tolerability profiles. By use of iTBS, the number of patients treated per day with current rTMS devices can be increased several times without compromising clinical effectiveness. Funding: Canadian Institutes of Health Research.

Lancet (London, England) · randomised controlled trial · 938 citationsread the source →

Mediating Mechanisms in a Physical Activity Intervention: A Test of Habit Formation

BACKGROUND: A recent randomized controlled trial found that an intervention focused on developing an exercise habit increased weekly minutes of moderate to vigorous physical activity (MVPA) over 8 wk compared to a control group. The purpose of the current study was to test if changes in habit, as well as other behavioral strategy constructs from the Multi-Process Action Control Test, mediated between group condition and MVPA (self-report and accelerometry). METHODS: Inactive new gym members (N = 94) were randomized into control or experimental (habit-building) groups. RESULTS: No construct entirely explained mediation condition (experimental and control) and changes in MVPA measured by accelerometry. Self-report MVPA found affective judgments, behavioral regulation, and preparatory habit to be mediated between group (experimental/control conditions) and changes in behavior (β = 0.36, 95% confidence interval [.05-.78]). CONCLUSIONS: Self-reported and objectively measured behavior models demonstrated complete and partial mediation, respectively. New gym members could benefit from successful behavioral enactment by developing constructs to support habit formation.

Journal of Sport and Exercise Psychology · randomised controlled trial · 40 citationsread the source →

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

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

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

Do Parents Benefit From Help When Completing a Self-Guided Parenting Program Online? A Randomized Controlled Trial Comparing Triple P Online With and Without Telephone Support.

In response to recent increases in the dissemination of Web-based parenting supports, an important consideration is whether the core benefits of self-directed participation in online parenting interventions are counterbalanced by issues such as high dropout and noncompletion rates commonly reported within the Internet intervention literature. This study outlines a randomized controlled trial of Triple P Online, a Web-based variant of the Triple P-Positive Parenting Program, delivered with varied levels of support scaffolding. Participants were 183 parents of children between 1 and 8 years of age with concerns about their child's behavior and at least one area of disadvantage or family difficulty. Participants were randomized to self-directed Triple P Online, telephone-supported Triple P Online, or a wait-list control. Primary outcomes measured at baseline, postintervention, and 5-month follow-up were negative parenting styles and child behavior problems. Secondary outcomes included parent confidence, anger, and adjustment; relationship quality; program engagement; and parent satisfaction. Self-directed participants showed short-term treatment effects, including reductions in overall negative parenting and frequency of child behavior problems, while practitioner support led to greater improvements in negative parenting and intensity of difficult child behaviors. Participants in the supported condition were also more likely to complete modules and reported greater program satisfaction. At follow-up, 50% of outcomes for the self-directed condition were significantly better than the control, while 94% of outcomes were significantly better than the control in the practitioner-supported condition. Although self-directed online approaches to parenting intervention are promising, this research highlights how minimal support can improve effective engagement and enhance outcomes for families.

Behavior therapy · randomised controlled trial · 64 citationsread the source →

Effect of an Internet-Delivered Stepped-Care Program vs In-Person Cognitive Behavioral Therapy on Obsessive-Compulsive Disorder Symptoms in Children and Adolescents: A Randomized Clinical Trial.

Importance: In most countries, young people with obsessive-compulsive disorder have limited access to specialist cognitive behavioral therapy (CBT), a first-line treatment. Objective: To investigate whether internet-delivered CBT implemented in a stepped-care model is noninferior to in-person CBT for pediatric obsessive-compulsive disorder. Design, setting and participants: A randomized clinical noninferiority trial conducted at 2 specialist child and adolescent mental health clinics in Sweden. Participants included 152 individuals aged 8 to 17 years with obsessive-compulsive disorder. Enrollment began in October 2017 and ended in May 2019. Follow-up ended in April 2020. Interventions: Participants randomized to the stepped-care group (n = 74) received internet-delivered CBT for 16 weeks. Nonresponders at the 3-month follow-up were then offered a course of traditional face-to-face treatment. Participants randomized to the control group (n = 78) immediately received in-person CBT for 16 weeks. Nonresponders at the 3-month follow-up received additional face-to-face treatment. Main outcomes and measures: The primary outcome was the masked assessor-rated Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score at the 6-month follow-up. The scale includes 10 items rated from 0 (no symptoms) to 4 (extreme symptoms), yielding a total score range of 0 to 40, with higher scores indicating greater severity. Assessors were masked to treatment allocation at pretreatment, posttreatment, 3-month follow-up, and 6-month follow-up assessments. The predefined noninferiority margin was 4 points on the CY-BOCS. Results: Among the 152 randomized participants (mean age, 13.4 years; 94 [62%] females), 151 (99%) completed the trial. At the 3-month follow-up, 34 participants (46%) in the stepped-care group and 23 (30%) in the in-person CBT group were nonresponders. At the 6-month follow-up, the CY-BOCS score was 11.57 points in the stepped-care group vs 10.57 points in the face-to-face treatment group, corresponding to an estimated mean difference of 0.91 points ([1-sided 97.5% CI, -∞ to 3.28]; P for noninferiority = .02). Increased anxiety (30%-36%) and depressive symptoms (20%-28%) were the most frequently reported adverse events in both groups. There were 2 unrelated serious adverse events (1 in each group). Conclusions and relevance: Among children and adolescents with obsessive-compulsive disorder, treatment with an internet-delivered CBT program followed by in-person CBT if necessary compared with in-person CBT alone resulted in a noninferior difference in symptoms at the 6-month follow-up. Further research is needed to understand the durability and generalizability of these findings. Trial registration: ClinicalTrials.gov Identifier: NCT03263546.

JAMA · randomised controlled trial · 42 citationsread the source →

Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms: A Randomized Clinical Trial.

Importance: Although an estimated 30 million people meet criteria for alcohol use disorder (AUD), few receive appropriate pharmacotherapy. A more personalized, symptom-specific, approach might improve efficacy and acceptance. Objective: To examine whether gabapentin would be useful in the treatment of AUD, especially in those with the most alcohol withdrawal symptoms. Design, setting, and participants: This double-blind randomized clinical trial conducted between November 2014 and June 2018 evaluated gabapentin vs placebo in community-recruited participants screened and treated in an academic outpatient setting over a 16-week treatment period. A total of 145 treatment-seeking individuals who met Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for AUD and were not receiving other AUD intervention were screened, and 96 who also met recent alcohol withdrawal criteria were randomized to treatment after 3 abstinent days. Daily drinking was recorded, and percentage of disialo carbohydrate-deficient transferrin in the blood, a heavy drinking marker, was collected at baseline and monthly during treatment. Interventions: Gabapentin up to 1200 mg/d, orally, vs placebo along with 9 medical management visits (20 minutes each). Main outcomes and measures: The percentage of individuals with no heavy drinking days and those with total abstinence were compared between treatment groups and further evaluated based on prestudy alcohol withdrawal symptoms. Results: Of 96 randomized individuals, 90 were evaluable (44 in the gabapentin arm and 46 in the placebo arm), with a mean (SD) age of 49.6 (10.1) years; 69 were men (77%) and 85 were white (94%). The evaluable participants had 83% baseline heavy drinking days (4 or more drinks/day for women, 5 or more for men) and met 4.5 alcohol withdrawal criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). More gabapentin-treated individuals had no heavy drinking days (12 of 44 participants [27%]) compared with placebo (4 of 46 participants [9%]), a difference of 18.6% (95% CI, 3.1-34.1; P = .02; number needed to treat [NNT], 5.4), and more total abstinence (8 of 44 [18%]) compared with placebo (2 of 46 [4%]), a difference of 13.8% (95% CI, 1.0-26.7; P = .04; NNT, 6.2). The prestudy high-alcohol withdrawal group had positive gabapentin effects on no heavy drinking days (P < .02; NNT, 3.1) and total abstinence (P = .003; NNT, 2.7) compared with placebo, while within the low-alcohol withdrawal group, there were no significant differences. These findings were similar for other drinking variables, where gabapentin was more efficacious than placebo in the high-alcohol withdrawal group only. Gabapentin caused more dizziness, but this did not affect efficacy. Conclusions and relevance: These data, combined with others, suggest gabapentin might be most efficacious in people with AUD and a history of alcohol withdrawal symptoms. Future studies should evaluate sleep changes and mood during early recovery as mediators of gabapentin efficacy. Trial registration: ClinicalTrials.gov Identifier: NCT02349477.

JAMA internal medicine · randomised controlled trial · 119 citationsread the source →

Effect of the Promoting Resilience in Stress Management Intervention for Parents of Children With Cancer (PRISM-P): A Randomized Clinical Trial.

Importance: Parents of children with serious illness, such as cancer, experience high stress and distress. Few parent-specific psychosocial interventions have been evaluated in randomized trials. Objective: To determine if individual- or group-based delivery of a novel intervention called Promoting Resilience in Stress Management for Parents (PRISM-P) improves parent-reported resilience compared with usual care. Design, setting, and participants: This parallel, phase 2 randomized clinical trial with enrollment from December 2016 through December 2018 and 3-month follow-up was conducted at Seattle Children's Hospital. English-speaking parents or guardians of children who were 2 to 24 years old, who had received a diagnosis of a new malignant neoplasm 1 to 10 weeks prior to enrollment, and who were receiving cancer-directed therapy at Seattle Children's Hospital were included. Parents were randomized 1:1:1 to the one-on-one or group PRISM-P intervention or to usual care. Data were analyzed in 2019 (primary analyses from January to March 2019; final analyses in July 2019). Interventions: The PRISM-P is a manualized, brief intervention targeting 4 skills: stress management, goal setting, cognitive reframing, and meaning making. For one-on-one delivery, skills were taught privately and in person for 30 to 60 minutes approximately every other week. For group delivery, the same skills were taught in a single session with at least 2 parents present. Main outcomes and measures: Participants completed patient-reported outcome surveys at enrollment and at 3 months. Linear regression modeling evaluated associations in the intention-to-treat population between each delivery format and the primary outcome (Connor-Davidson Resilience Scale scores, ranging from 0 to 40, with higher scores reflecting greater resilience) and secondary outcomes (benefit finding, social support, health-related quality of life, stress, and distress) at 3 months. Results: In total, 94 parents enrolled, were randomized to 1 of the 3 groups, and completed baseline surveys (32 parents in one-on-one sessions, 32 in group sessions, and 30 in usual care). Their median (interquartile range) ages were 35 to 38 (31-44) years across the 3 groups, and they were predominantly white, college-educated mothers. Their children had median (interquartile range) ages of 5 to 8 (3-14) years; slightly more than half of the children were boys, and the most common cancer type was leukemia or lymphoma. One-on-one PRISM-P delivery was significantly associated with improvement compared with usual care in parent-reported outcomes for resilience (β, 2.3; 95% CI, 0.1-4.6; P = .04) and for benefit finding (β, 0.5; 95% CI, 0.2-0.8; P = .001). No significant associations were detected between either platform and other parent-reported outcomes. Conclusions and relevance: When delivered individually, PRISM-P was associated with improved parent-reported resilience and benefit finding. This scalable psychosocial intervention may help parents cope and find meaning after their child receives a diagnosis of a serious illness. Trial registration: ClinicalTrials.gov identifier: NCT02998086.

JAMA network open · randomised controlled trial · 90 citationsread the source →

Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2.

Purpose: The objective was to compare laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer. Patients and methods: Patients with clinical stage I to IIA uterine cancer were randomly assigned to laparoscopy (n = 1,696) or open laparotomy (n = 920), including hysterectomy, salpingo-oophorectomy, pelvic cytology, and pelvic and para-aortic lymphadenectomy. The main study end points were 6-week morbidity and mortality, hospital length of stay, conversion from laparoscopy to laparotomy, recurrence-free survival, site of recurrence, and patient-reported quality-of-life outcomes. Results: Laparoscopy was initiated in 1,682 patients and completed without conversion in 1,248 patients (74.2%). Conversion from laparoscopy to laparotomy was secondary to poor visibility in 246 patients (14.6%), metastatic cancer in 69 patients (4.1%), bleeding in 49 patients (2.9%), and other cause in 70 patients (4.2%). Laparoscopy had fewer moderate to severe postoperative adverse events than laparotomy (14% v 21%, respectively; P < .0001) but similar rates of intraoperative complications, despite having a significantly longer operative time (median, 204 v 130 minutes, respectively; P < .001). Hospitalization of more than 2 days was significantly lower in laparoscopy versus laparotomy patients (52% v 94%, respectively; P < .0001). Pelvic and para-aortic nodes were not removed in 8% of laparoscopy patients and 4% of laparotomy patients (P < .0001). No difference in overall detection of advanced stage (stage IIIA, IIIC, or IVB) was seen (17% of laparoscopy patients v 17% of laparotomy patients; P = .841). Conclusion: Laparoscopic surgical staging for uterine cancer is feasible and safe in terms of short-term outcomes and results in fewer complications and shorter hospital stay. Follow-up of these patients will determine whether surgical technique impacts pattern of recurrence or disease-free survival.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · randomised controlled trial · 829 citationsread the source →

Meditation or exercise for preventing acute respiratory infection: a randomized controlled trial.

Purpose: This study was designed to evaluate potential preventive effects of meditation or exercise on incidence, duration, and severity of acute respiratory infection (ARI) illness. Methods: Community-recruited adults aged 50 years and older were randomized to 1 of 3 study groups: 8-week training in mindfulness meditation, matched 8-week training in moderate-intensity sustained exercise, or observational control. The primary outcome was area-under-the-curve global illness severity during a single cold and influenza season, using the Wisconsin Upper Respiratory Symptom Survey (WURSS-24) to assess severity. Health care visits and days of missed work were counted. Nasal wash collected during ARI illness was assayed for neutrophils, interleukin-8, and viral nucleic acid. Results: Of 154 adults randomized into the study, 149 completed the trial (82% female, 94% white, mean age 59.3 ± 6.6 years). There were 27 ARI episodes and 257 days of ARI illness in the meditation group (n = 51), 26 episodes and 241 illness days in the exercise group (n = 47), and 40 episodes and 453 days in the control group (n = 51). Mean global severity was 144 for meditation, 248 for exercise, and 358 for control. Compared with control, global severity was significantly lower for meditation (P = .004). Both global severity and total days of illness (duration) trended toward being lower for the exercise group (P=.16 and P=.032, respectively), as did illness duration for the meditation group (P=.034). Adjusting for covariates using zero-inflated multivariate regression models gave similar results. There were 67 ARI-related days of-work missed in the control group, 32 in the exercise group (P = .041), and 16 in the meditation group (P <.001). Health care visits did not differ significantly. Viruses were identified in 54% of samples from meditation, 42% from exercise, and 54% from control groups. Neutrophil count and interleukin-8 levels were similar among intervention groups. Conclusions: Training in meditation or exercise may be effective in reducing ARI illness burden.

Annals of family medicine · randomised controlled trial · 91 citationsread the source →

A randomized trial to improve the quality of treatment for panic and generalized anxiety disorders in primary care.

Context: Panic disorder and generalized anxiety disorder are prevalent in primary care, associated with poor functional outcomes, and are often unrecognized and ineffectively treated by primary care physicians. Objective: To examine whether telephone-based collaborative care for panic and generalized anxiety disorders improves clinical and functional outcomes more than the usual care provided by primary care physicians. Design: Randomized controlled trial. Setting: Four Pittsburgh area primary care practices linked by a common electronic medical record system. Patients A total of 191 adults aged 18 to 64 years with panic and/or generalized anxiety disorder who were recruited from July 2000 to April 2002. Intervention Patients were randomly assigned to a telephone-based care management intervention (n = 116) or to notification alone of the anxiety disorder to patients and their physicians (usual care, n = 75). The intervention involved non-mental health professionals who provided patients with psychoeducation, assessed preferences for guideline-based care, monitored treatment responses, and informed physicians of their patients' care preferences and progress via an electronic medical record system under the direction of study investigators. Main outcome measures: Independent blinded assessments of anxiety and depressive symptoms, mental health-related quality of life, and employment status at baseline, 2-, 4-, 8-, and 12-month follow-up. Results: At 12-month follow-up, intervention patients reported reduced anxiety (effect size [ES], 0.33-0.38; 95% confidence interval [CI], 0.04 to 0.67; P</=.02) and depressive symptoms (ES, 0.35; 95% CI, 0.25-0.46; P = .03); improved mental health-related quality of life (ES, 0.39; 95% CI, 0.10 to 0.68; P = .01); and larger improvements relative to baseline in hours worked per week (5.7; 95% CI, 0.1 to 11.3; P = .05) and fewer work days absent in the past month (-2.6; 95% CI, - 4.8 to -0.3; P = .03) than usual care patients. If working at baseline, more intervention patients than usual care patients remained working at 12-month follow-up (94% vs 79% [15% absolute difference, 0.7%-28.6%]; P = .04). Conclusions: Telephone-based collaborative care for panic disorder and generalized anxiety disorder is more effective than usual care at improving anxiety symptoms, health-related quality of life, and work-related outcomes.

Archives of general psychiatry · randomised controlled trial · 105 citationsread the source →

Whole-gland ablation of localized prostate cancer with high-intensity focused ultrasound: oncologic outcomes and morbidity in 1002 patients.

Background: High-intensity focused ultrasound (HIFU) is a nonsurgical therapy for selected patients with localized prostate cancer (PCa). Objective: The long-term oncologic and morbidity outcomes of primary HIFU therapy for localized PCa were evaluated in a prospective, single-arm, single-institution cohort study. Design, setting, and participants: Participants were patients treated with HIFU for localized PCa from 1997 to 2009. Excluded were patients with local recurrence following radiotherapy. A second HIFU session was systematically performed in patients with biopsy-proven local recurrence. Intervention: Whole-gland prostate ablation with transrectal HIFU. Outcome measurements and statistical analysis: Incontinence was assessed using the Ingelman-Sundberg score, and potency was assessed using the five-item version of the International Index of Erectile Function (IIEF-5) scores. Primary outcomes were survival rates (biochemical-free, cancer-specific, metastasis-free, and overall survival). Secondary outcomes were morbidity rates. Median follow-up was 6.4 yr (range: 0.2-13.9). The Kaplan-Meier method was used to determine survival estimates, and multivariate analysis was used to determine predictive factors of biochemical progression. Results and limitations: A total of 1002 patients were included. The median nadir prostate-specific antigen (PSA) was 0.14 ng/ml, with 63% of patients reaching a nadir PSA ≤0.3 ng/ml. Sixty percent of patients received one HIFU session, 38% received two sessions, and 2% received three sessions. The 8-yr biochemical-free survival rates (Phoenix definition) were 76%, 63%, and 57% for low-, intermediate-, and high-risk patients, respectively (p < 0.001). At 10 yr, the PCa-specific survival rate and metastasis-free survival rate (MFSR) were 97% and 94%, respectively. Salvage therapies included external-beam radiation therapy (EBRT) (13.8%), EBRT plus androgen-deprivation therapy (ADT) (9.7%), and ADT alone (12.1%). Severe incontinence and bladder outlet obstruction decreased with refinement in the technology, from 6.4% and 34.9% to 3.1% and 5.9%, respectively. Limitations included the fact that the study was a single-arm study without a comparison group, technological improvements, changes in surgical protocol during the study, and the use of ADT to downsize the prostate in 39% of patients. Conclusions: HIFU is a potentially effective treatment of localized PCa, with a low PCa-specific mortality rate and a high MFSR at 10 yr as well as acceptable morbidity.

European urology · clinical trial · 135 citationsread the source →

International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

Background: In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses. Methods: The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. Findings: We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and -2·69 mm (3·2) for head circumference; 0·83 mm (0·9), -0·05 mm (0·8), and -0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and -1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and -4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and -0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. Interpretation: We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. Funding: Bill & Melinda Gates Foundation.

Lancet (London, England) · cohort or longitudinal · 589 citationsread the source →

Spanish-Latin American multicenter study of attitudes toward organ donation among personnel from hospital healthcare centers.

Introduction: Hospital personnel are a group which has an influence on the opinion of the rest of the population about healthcare matters. Any unfavorable attitude of this group would be an obstacle to an increase in organ donation. Objective: To analyze the attitude of hospital workers toward the donation of one's own organs in Spanish and Latin American hospitals and to determine the factors affecting this attitude. Material and method: Eleven hospitals from the "International Collaborative Donor Project" were selected, 3 in Spain, 5 in Mexico, 2 in Cuba and one in Costa Rica. A random sample was stratified by the type of service and job category. Attitude toward donation and transplantation was assessed using a validated survey. The questionnaire was completed anonymously and was self-administered. Statistical analysis: Student's t-test, the χ2 test and logistic regression analysis. Results: Of the 2,785 workers surveyed, 822 were from Spain, 1,595 from Mexico, 202 from Cuba and 166 from Costa Rica and 79% (n=2,191) were in favor of deceased organ donation. According to country, 94% (n=189) of Cubans were in favor, compared to 82% (n=1,313) of the Mexicans, 73% (n=121) of the Costa Ricans and 69% (n=568) of the Spanish (P<.001). In the multivariate analysis, the following variables had the most specific weight: 1) originating from Cuba (odds ratio=8.196; P<.001); 2) being a physician (OR= 2.544; P<.001); 3) performing a job related to transplantation (OR = 1.610; P=.005); 4) having discussed the subject of donation and transplantation within the family (OR= 3.690; P<.001); 5) having a partner with a favorable attitude toward donation and transplantation (OR= 3.289; P<.001); 6) a respondent's belief that his or her religion is in favor of donation and transplantation (OR= 3.021; P=.001); 7) not being concerned about the possible mutilation of the body after donation (OR= 2.994; P<.001); 8) the preference for other options apart from burial for treating the body after death (OR= 2.770; P<.001); and 9) acceptance of carrying out an autopsy if one were needed (OR= 2.808; P<.001). Conclusions: Hospital personnel in Spanish and Latin American healthcare centers had a favorable attitude toward donation, although 21% of respondents were not in favor of donating. This attitude was more favorable among Latin American workers and was very much conditioned by job-related and psychosocial factors.

Cirugia espanola · cohort or longitudinal · 40 citationsread the source →

Distress, delay of gratification and preference for palliative care in men with prostate cancer.

Background: Patient-centered cancer care standards include routine psychosocial distress screening and referral for supportive care services. Although many cancer patients report psychosocial distress that could be alleviated by supportive services including palliative care, patients often decline such services for reasons that are poorly understood. Research on decision-making suggests that during periods of acute distress, individuals have more difficulty prioritizing long-term over immediate gains. Thus, distressed cancer patients may prioritize immediate gains (e.g., avoidance of palliative care discussions in the moment) over longer-term gains (e.g., improved quality of life in the future). Method: This study investigated the associations between psychosocial distress, difficulties with delay of gratification (tendency to prioritize short-term over longer-term gains), and preference for palliative care in a sample of 212 men with a history of prostate cancer (94% white men and 27% advanced stage, age M = 62, SD = 8). It was hypothesized that psychosocial distress would be associated with lower preferences for palliative care, and this association would be explained, in part, by difficulty delaying gratification. Self-report measures included the depression anxiety stress scales, delay of gratification inventory, and ratings on an item assessing preferences for palliative care. Results: Consistent with the hypothesis, mediation models confirmed that the association of psychosocial distress with lower preference for palliative care was mediated by delay of gratification. Conclusions: Findings suggest that distressed prostate cancer patients may benefit from additional support managing the emotional aspects of medical decisions and weighing immediate versus delayed outcomes.

Psycho-oncology · 14 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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[PMID: 9652398] CrossrefMedlineGoogle Scholar27. Heck S, Bender K, Kullmann M, Gottlicher M, Herrlich P, Cato AC. IB-independent downregulation of NF-B activity by glucocorticoid receptor. EMBO J. 1997;16:4698-707. [PMID: 9303314] CrossrefMedlineGoogle Scholar28. Reichardt HM, Tuckermann JP, Gottlicher M, Vujic M, Weih F, Angel P, . Repression of inflammatory responses in the absence of DNA binding by the glucocorticoid receptor. EMBO J. 2001;20:7168-73. [PMID: 11742993] CrossrefMedlineGoogle Scholar29. Hart L, Lim S, Adcock I, Barnes PJ, Chung KF. Effects of inhaled corticosteroid therapy on expression and DNA-binding activity of nuclear factor B in asthma. Am J Respir Crit Care Med. 2000;161:224-31. [PMID: 10619824] CrossrefMedlineGoogle Scholar30. Imhof A, Wolffe AP. Transcription: gene control by targeted histone acetylation. Curr Biol. 1998;8:R422-4. [PMID: 9637914] CrossrefMedlineGoogle Scholar31. Peterson CL. HDAC's at work: everyone doing their part. Mol Cell. 2002;9:921-2. [PMID: 12049726] CrossrefMedlineGoogle Scholar32. Berger SL. An embarrassment of niches: the many covalent modifications of histones in transcriptional regulation. Oncogene. 2001;20:3007-13. [PMID: 11420715] CrossrefMedlineGoogle Scholar33. Bannister AJ, Schneider R, Kouzarides T. Histone methylation: dynamic or static? Cell. 2002;109:801-6. [PMID: 12110177] CrossrefMedlineGoogle Scholar34. Kagoshima M, Wilcke T, Ito K, Tsaprouni L, Barnes PJ, Punchard N, . Glucocorticoid-mediated transrepression is regulated by histone acetylation and DNA methylation. Eur J Pharmacol. 2001;429:327-34. [PMID: 11698053] CrossrefMedlineGoogle Scholar35. Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293:1074-80. [PMID: 11498575] CrossrefMedlineGoogle Scholar36. Bergmann M, Barnes PJ, Newton R. Molecular regulation of granulocyte macrophage colony-stimulating factor in human lung epithelial cells by interleukin (IL)-1, IL-4, and IL-13 involves both transcriptional and post-transcriptional mechanisms. Am J Respir Cell Mol Biol. 2000;22:582-9. [PMID: 10783130] CrossrefMedlineGoogle Scholar37. Caelles C, Gonzalez-Sancho JM, Munoz A. Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 1997;11:3351-64. [PMID: 9407028] CrossrefMedlineGoogle Scholar38. Vanden Berghe W, Vermeulen L, De Wilde G, De Bosscher K, Boone E, Haegeman G. Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol. 2000;60:1185-95. [PMID: 11007957] CrossrefMedlineGoogle Scholar39. Lasa M, Brook M, Saklatvala J, Clark AR. Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. Mol Cell Biol. 2001;21:771-80. [PMID: 11154265] CrossrefMedlineGoogle Scholar40. Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR. Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38. Mol Cell Biol. 2002;22:7802-11. [PMID: 12391149] CrossrefMedlineGoogle Scholar41. Barnes PJ. Scientific rationale for inhaled combination therapy with long-acting 2-agonists and corticosteroids. Eur Respir J. 2002;19:182-91. [PMID: 11843317] CrossrefMedlineGoogle Scholar42. Adcock IM, Stevens DA, Barnes PJ. Interactions of glucocorticoids and 2-agonists. Eur Respir J. 1996;9:160-8. [PMID: 8834349] CrossrefMedlineGoogle Scholar43. Mak JC, Nishikawa M, Shirasaki H, Miyayasu K, Barnes PJ. Protective effects of a glucocorticoid on downregulation of pulmonary 2-adrenergic receptors in vivo. J Clin Invest. 1995;96:99-106. [PMID: 7615841] CrossrefMedlineGoogle Scholar44. Mak JC, Hisada T, Salmon M, Barnes PJ, Chung KF. Glucocorticoids reverse IL-1-induced impairment of -adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinases. Br J Pharmacol. 2002;135:987-96. [PMID: 11861327] CrossrefMedlineGoogle Scholar45. Eickelberg O, Roth M, Lorx R, Bruce V, Rudiger J, Johnson M, . Ligand-independent activation of the glucocorticoid receptor by 2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem. 1999;274:1005-10. [PMID: 9873044] CrossrefMedlineGoogle Scholar46. Pang L, Knox AJ. Regulation of TNF--induced eotaxin release from cultured human airway smooth muscle cells by 2-agonists and corticosteroids. FASEB J. 2001;15:261-269. [PMID: 11149914] CrossrefMedlineGoogle Scholar47. Korn SH, Wouters EF, Wesseling G, Arends JW, Thunnissen FB. Interaction between glucocorticoids and 2-agonists: and glucocorticoid-receptor mRNA expression in human bronchial epithelial cells. Biochem Pharmacol. 1998;56:1561-9. [PMID: 9973176] CrossrefMedlineGoogle Scholar48. Usmani OS, Maneechotesuwan K, Adcock IM, Barnes PJ. Glucocorticoid receptor activation following inhaled fluticasone and salmeterol [Abstract]. Am J Respir Crit Care Med. 2002;165:A616. Google Scholar49. Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med. 2003;167:813-8. [PMID: 12623857] CrossrefMedlineGoogle Scholar50. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, . A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci U S A. 2002;99:8921-6. [PMID: 12070353] CrossrefMedlineGoogle Scholar51. Evans DJ, Taylor DA, Zetterstrom O, Chung KF, O'Connor BJ, Barnes PJ. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med. 1997;337:1412-8. [PMID: 9358138] CrossrefMedlineGoogle Scholar52. Ukena D, Harnest U, Sakalauskas R, Magyar P, Vetter N, Steffen H, . Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma. Eur Respir J. 1997;10:2754-60. [PMID: 9493656] CrossrefMedlineGoogle Scholar53. Lim S, Jatakanon A, Gordon D, Macdonald C, Chung KF, Barnes PJ. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice. Thorax. 2000;55:837-41. [PMID: 10992535] CrossrefMedlineGoogle Scholar54. Szefler SJ, Leung DY. Glucocorticoid-resistant asthma: pathogenesis and clinical implications for management. Eur Respir J. 1997;10:1640-7. [PMID: 9230260] CrossrefMedlineGoogle Scholar55. Barnes PJ. Steroid-resistant asthma. Eur Resp Rev. 2000;10:74-8. Google Scholar56. Spahn JD, Szefler SJ, Surs W, Doherty DE, Nimmagadda SR, Leung DY. A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity. J Immunol. 1996;157:2654-9. [PMID: 8805670] MedlineGoogle Scholar57. Irusen E, Matthews JG, Takahashi A, Barnes PJ, Chung KF, Adcock IM. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol. 2002;109:649-57. [PMID: 11941315] CrossrefMedlineGoogle Scholar58. Hamid QA, Wenzel SE, Hauk PJ, Tsicopoulos A, Wallaert B, Lafitte JJ, . Increased glucocorticoid receptor in airway cells of glucocorticoid-insensitive asthma. Am J Respir Crit Care Med. 1999;159:1600-4. [PMID: 10228133] CrossrefMedlineGoogle Scholar59. Gagliardo R, Chanez P, Vignola AM, Bousquet J, Vachier I, Godard P, . Glucocorticoid receptor and in glucocorticoid dependent asthma. Am J Respir Crit Care Med. 2000;162:7-13. [PMID: 10903212] CrossrefMedlineGoogle Scholar60. Corrigan CJ, Brown PH, Barnes NC, Szefler SJ, Tsai JJ, Frew AJ, . Glucocorticoid resistance in chronic asthma. Glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics, and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro. Am Rev Respir Dis. 1991;144:1016-25. [PMID: 1952426] CrossrefMedlineGoogle Scholar61. Adcock IM, Lane SJ, Brown CR, Lee TH, Barnes PJ. Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma. J Exp Med. 1995;182:1951-8. [PMID: 7500041] CrossrefMedlineGoogle Scholar62. Matthews JG, Ito K, Barnes PJ, Adcock IM. Corticosteroid-resistant and corticosteroid-dependent asthma: two clinical phenotypes can be associated with the same in vitro defects in nuclear translocation and acetylation of histone 4 [Abstract]. Am J Respir Crit Care Med. 2000;161:A189. Google Scholar63. Keatings VM, Jatakanon A, Worsdell YM, Barnes PJ. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997;155:542-8. [PMID: 9032192] CrossrefMedlineGoogle Scholar64. Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:1635-9. [PMID: 10556133] CrossrefMedlineGoogle Scholar65. Nightingale JA, Rogers DF, Fan Chung K, Barnes PJ. No effect of inhaled budesonide on the response to inhaled ozone in normal subjects. Am J Respir Crit Care Med. 2000;161:479-86. [PMID: 10673189] CrossrefMedlineGoogle Scholar66. Culpitt SV, Rogers DF, Shah P, De Matos C, Russell RE, Donnelly LE, . Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:24-31. [PMID: 12406856] CrossrefMedlineGoogle Scholar67. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J. 2001;15:1110-2. [PMID: 11292684] CrossrefMedlineGoogle Scholar68. Ito K, Watanabe S, Kharitonov S, Hanazawa T, Adcock IM, Barnes PJ. Histone deacetylase activity and gene expression in COPD patients [Abstract]. Eur Respir J. 2001;18:316S. MedlineGoogle Scholar69. Montuschi P, Collins JV, Ciabattoni G, Lazzeri N, Corradi M, Kharitonov SA, . Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000;162:1175-7. [PMID: 10988150] CrossrefMedlineGoogle Scholar70. Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids. New developments. Am J Respir Crit Care Med. 1998;157:S1-53. [PMID: 9520807] CrossrefMedlineGoogle Scholar71. Heck S, Kullmann M, Gast A, Ponta H, Rahmsdorf HJ, Herrlich P, . A distinct modulating domain in glucocorticoid receptor monomers in the repression of activity of the transcription factor AP-1. EMBO J. 1994;13:4087-95. [PMID: 8076604] CrossrefMedlineGoogle Scholar72. Adcock IM, Nasuhara Y, Stevens DA, Barnes PJ. Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-B and lack of I-B involvement. Br J Pharmacol. 1999;127:1003-11. [PMID: 10433509] CrossrefMedlineGoogle Scholar73. Vayssiere BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, . Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol. 1997;11:1245-55. [PMID: 9259316] CrossrefMedlineGoogle Scholar74. Belvisi MG, Wicks SL, Battram CH, Bottoms SE, Redford JE, Woodman P, . Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity. J Immunol. 2001;166:1975-82. [PMID: 11160246] CrossrefMedlineGoogle Scholar75. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, . Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell. 2002;110:93-105. [PMID: 12151000] CrossrefMedlineGoogle Scholar76. Barnes PJ. New treatments for COPD. Nat Rev Drug Discov. 2002;1:437-46. [PMID: 12119745] CrossrefMedlineGoogle Scholar77. Ito K, Lim S, Chung KF, Barnes PJ, Adcock IM. Theophylline enhances histone deacetylase activity and restores glucocorticoid function during oxidative stress [Abstract]. Am J Respir Crit Care Med. 2002;165:A625. Google Scholar Author, Article, and Disclosure InformationAffiliations: From National Heart and Lung Institute, Imperial College, London, United Kingdom. Disclosures:Grants received: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca); Grants pending: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca).Corresponding Author: P.J. Barnes, DM, DSc, Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom; e-mail, p.j.[email protected]ac.uk. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNanotechnology based advanced therapeutic strategies for targeting interleukins in chronic respiratory diseasesLipopolysaccharide Regulates Pro- and Anti-Inflammatory Cytokines, Corticosterone, and Melatonin in ToadsThe central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to interventionAsthma and COVID-19: Emphasis on Adequate of as of and as a Effect of the resistance in asthma: and molecular effects of on a of allergic between and and gene expression of glucocorticoid and receptors from the for of human respiratory with glucocorticoids in the treatment of asthma: of the oral corticosteroids and persistent in from the asthma to bronchial asthma as for A of of Melatonin and Glucocorticoid with in the a between Melatonin and of in Steroid Drug by of proteins during the Efficacy of to in a of corticosteroids in asthma: the between and the novel mode of action of the Association and 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Annals of Internal Medicine · review · 370 citationsread the source →

The cross-sectional association of stressful life events with depression severity among patients with hypertension and diabetes in Malawi.

Depressive disorders are a leading cause of global morbidity and remain disproportionately high in low- and middle-income settings. Stressful life events (SLEs) are known risk factors for depressive episodes and worsened depressive severity, yet are under-researched in comparison to other depression risk factors. As depression is often comorbid with hypertension, diabetes, and other noncommunicable diseases (NCDs), research into this relationship among patients with NCDs is particularly relevant to increasing opportunities for integrated depression and NCD care. This study aims to estimate the cross-sectional association between SLEs in the three months preceding baseline interviews and baseline depressive severity among patients with at least mild depressive symptoms who are seeking NCD care at 10 NCD clinics across Malawi. SLEs were measured by the Life Events Survey and depressive severity (mild vs. moderate to severe) was measured by the Patient Health Questionnaire-9. The study population (n = 708) was predominately currently employed, grand multiparous (5-8 children) women with a primary education level. Two thirds (63%) had mild depression while 26%, 8%, and 3% had moderate, moderately severe, and severe depression, respectively. Nearly all participants (94%) reported at least one recent SLE, with the most common reported SLEs being financial stress (48%), relationship changes (45%), death of a family member or friend (41%), or serious illness of a family member or friend (39%). Divorce/separation, estrangement from a family member, losing source of income, and major new health problems were significant predictors of greater (moderate or severe) depressive severity compared to mild severity. Having a major new health problem or experiencing divorce/separation resulted in particularly high risk of more severe depression. After adjustment, each additional SLE was associated with a 9% increased risk of moderate or worse depressive severity compared to mild depressive severity (RR: 1.09; (95% CI: 1.05, 1.13), p<0.0001). Among patients with NCDs with at least mild depressive symptoms, SLEs in the prior 3 months were associated with greater depressive severity. While many SLEs may not be preventable, this research suggests that assessment of SLEs and teaching of positive coping strategies when experiencing SLEs may play an important role in integrated NCD and depression treatment models.

PloS one · 3 citationsread the source →

Prevalence of post-traumatic stress disorder and common mental disorders in health-care workers in England during the COVID-19 pandemic: a two-phase cross-sectional study.

Background: Previous studies on the impact of the COVID-19 pandemic on the mental health of health-care workers have relied on self-reported screening measures to estimate the point prevalence of common mental disorders. Screening measures, which are designed to be sensitive, have low positive predictive value and often overestimate prevalence. We aimed to estimate prevalence of common mental disorders and post-traumatic stress disorder (PTSD) among health-care workers in England using diagnostic interviews. Methods: We did a two-phase, cross-sectional study comprising diagnostic interviews within a larger multisite longitudinal cohort of health-care workers (National Health Service [NHS] CHECK; n=23 462) during the COVID-19 pandemic. In the first phase, health-care workers across 18 NHS England Trusts were recruited. Baseline assessments were done using online surveys between April 24, 2020, and Jan 15, 2021. In the second phase, we selected a proportion of participants who had responded to the surveys and conducted diagnostic interviews to establish the prevalence of mental disorders. The recruitment period for the diagnostic interviews was between March 1, 2021 and Aug 27, 2021. Participants were screened with the 12-item General Health Questionnaire (GHQ-12) and assessed with the Clinical Interview Schedule-Revised (CIS-R) for common mental disorders or were screened with the 6-item Post-Traumatic Stress Disorder Checklist (PCL-6) and assessed with the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) for PTSD. Findings: The screening sample contained 23 462 participants: 2079 participants were excluded due to missing values on the GHQ-12 and 11 147 participants due to missing values on the PCL-6. 243 individuals participated in diagnostic interviews for common mental disorders (CIS-R; mean age 42 years [range 21-70]; 185 [76%] women and 58 [24%] men) and 94 individuals participated in diagnostic interviews for PTSD (CAPS-5; mean age 44 years [23-62]; 79 [84%] women and 15 [16%] men). 202 (83%) of 243 individuals in the common mental disorders sample and 83 (88%) of 94 individuals in the PTSD sample were White. GHQ-12 screening caseness for common mental disorders was 52·8% (95% CI 51·7-53·8). Using CIS-R diagnostic interviews, the estimated population prevalence of generalised anxiety disorder was 14·3% (10·4-19·2), population prevalence of depression was 13·7% (10·1-18·3), and combined population prevalence of generalised anxiety disorder and depression was 21·5% (16·9-26·8). PCL-6 screening caseness for PTSD was 25·4% (24·3-26·5). Using CAPS-5 diagnostic interviews, the estimated population prevalence of PTSD was 7·9% (4·0-15·1). Interpretation: The prevalence estimates of common mental disorders and PTSD in health-care workers were considerably lower when assessed using diagnostic interviews compared with screening tools. 21·5% of health-care workers met the threshold for diagnosable mental disorders, and thus might benefit from clinical intervention. Funding: UK Medical Research Council; UCL/Wellcome; Rosetrees Trust; NHS England and Improvement; Economic and Social Research Council; National Institute for Health and Care Research (NIHR) Biomedical Research Centre at the Maudsley and King's College London (KCL); NIHR Protection Research Unit in Emergency Preparedness and Response at KCL.

The lancet. Psychiatry · 57 citationsread the source →

Policy Actions to Address Weight-Based Bullying and Eating Disorders in Schools: Views of Teachers and School Administrators.

Background: Weight-related bullying is prevalent among youth and associated with adverse health consequences, including increased risk for body dissatisfaction and disordered eating behaviors, which are risk factors for eating disorders. Although concerns about these problems have stimulated calls for broader intervention efforts in schools, actions thus far have been limited. This study examined educators' perspectives about potential policy actions to address these issues in schools. Methods: Educators (N = 240) completed an online questionnaire assessing their support for 11 potential school-based policy actions to address weight-related bullying and eating disorders. Participants also rated policies according to their feasibility and potential for positive impact. Results: Forty-eight percent of participants observed weight-related bullying in their school and 99% expressed the importance of intervening in such incidents. A large majority (75%-94%) supported 8 of the 11 policies, especially actions requiring school-based health curriculum to include content on eating disorder prevention (94%), and addressing weight-bullying through antibullying policies (92%), staff training (89%), and school curriculum (89%). Strongly supported policies were viewed by participants as being the most impactful and feasible to implement. Conclusions: Educators recognize weight-related bullying and eating disorders as problems in their schools that warrant improved prevention and intervention efforts at the policy level.

The Journal of school health · 21 citationsread the source →

Psychological responses, mental health, and sense of agency for the dual challenges of climate change and the COVID-19 pandemic in young people in the UK: an online survey study.

Background: The COVID-19 pandemic and climate change are both significant and pressing global challenges, posing threats to public health and wellbeing. Young people are particularly vulnerable to the distress both crises can cause, but understanding of the varied psychological responses to both issues is poor. We aimed to investigate these responses and their links with mental health conditions and feelings of agency. Methods: We conducted an online survey between Aug 5 and Oct 26, 2020, targeting a diverse sample of young people (aged 16-24 years, n=530) in the UK. The survey was distributed using a combination of a survey panel (panel sample) and direct approaches to youth groups and schools who shared the survey with young people in their networks (community sample). We collected data on respondents' psychological responses to both climate change and the COVID-19 pandemic, their sense of agency to respond to each crisis, and the range of impacts on their lives. We also collected demographics data and screened for mental health and wellbeing indicators. We used non-parametric tests for most statistical comparisons. For paired samples, we used Wilcoxon's signed-rank test, and used Mann-Whitney U-tests or Kruskal-Wallis tests for two or more independent samples. Summed scale scores were considered as interval-level data and analysed with Student's t tests and ANOVAs. Effect sizes are reported as Cohen's d and partial eta-squared (η·2p), respectively. Findings: After excluding 18 suspected bots and 94 incomplete responses, 530 responses were retained for analysis. Of the 518 respondents who provided demographic data, 63% were female, 71·4% were White, and the mean family affluence score was 8·22 (SD 2·29). Most participants (n=343; 70%) did not report a history of diagnosis or treatment for a mental health disorder, but mental health scores indicated a common experience of (relatively mild) symptoms of anxiety, depression, and stress. Although UK youth reported more life disruption and concern for their future due to the COVID-19 pandemic, climate change was associated with significantly greater distress overall, particularly for individuals with low levels of generalised anxiety. The COVID-19 pandemic was more associated with feelings of anxiety, isolation, disconnection, and frustration; distress around loss and grief; and effects on quality of life. Climate change was more likely to evoke emotions such as interest and engagement, guilt, shame, anger, and disgust. The greater distress attributed to climate change overall was due, in particular, to higher levels of guilt, sense of personal responsibility, and greater distress triggered by upsetting media coverage. Agency to address climate change was associated with greater climate distress, but pandemic-related distress and agency were unrelated. Interpretation: The COVID-19 pandemic and climate change are affecting the wellbeing of UK young people in distinct ways, with implications for health service, policy, and research responses. There is a need for mental health practitioners, policy makers, and other societal actors to account for the complex relationship between climate agency, distress, and mental wellbeing in young people. Funding: Imperial College London.

The Lancet. Planetary health · 47 citationsread the source →

Using Online Screening in the General Population to Detect Participants at Clinical High-Risk for Psychosis.

Introduction: Identification of participants at clinical high-risk (CHR) for the development of psychosis is an important objective of current preventive efforts in mental health research. However, the utility of using web-based screening approaches to detect CHR participants at the population level has not been investigated. Methods: We tested a web-based screening approach to identify CHR individuals. Potential participants were invited to a website via e-mail invitations, flyers, and invitation letters involving both the general population and mental health services. Two thousand two hundred seventy-nine participants completed the 16-item version of the prodromal questionnaire (PQ-16) and a 9-item questionnaire of perceptual and cognitive aberrations (PCA) for the assessment of basic symptoms (BS) online. 52.3% of participants met a priori cut-off criteria for the PQ and 73.6% for PCA items online. One thousand seven hundred eighty-seven participants were invited for a clinical interview and n = 356 interviews were conducted (response rate: 19.9%) using the Comprehensive Assessment of At-Risk Mental State (CAARMS) and the Schizophrenia Proneness Interview, Adult Version (SPI-A). n = 101 CHR participants and n = 8 first-episode psychosis (FEP) were detected. ROC curve analysis revealed good to moderate sensitivity and specificity for predicting CHR status based on online results for both UHR and BS criteria (sensitivity/specificity: PQ-16 = 82%/46%; PCA = 94%/12%). Selection of a subset of 10 items from both PQ-16 and PCA lead to an improved of specificity of 57% while only marginally affecting sensitivity (81%). CHR participants were characterized by similar levels of functioning and neurocognitive deficits as clinically identified CHR groups. Conclusion: These data provide evidence for the possibility to identify CHR participants through population-based web screening. This could be an important strategy for early intervention and diagnosis of psychotic disorders.

Schizophrenia bulletin · 80 citationsread the source →

Feasibility, Acceptability, and Preliminary Efficacy of a Positive Affect Skills Intervention for Adults With Fibromyalgia.

Background and objectives: To examine the feasibility, acceptability, and preliminary efficacy of a positive affect skills intervention for middle-aged and older adults with fibromyalgia syndrome (FMS). Research design and methods: Ninety-five participants with FMS aged 50 and older (94% female) were randomized to 1 of 2 conditions: (a) Lessons in Affect Regulation to Keep Stress and Pain UndeR control (LARKSPUR; n = 49) or (b) emotion reporting/control (n = 46). LARKSPUR included 5 weeks of skill training that targeted 8 skills to help foster positive affect, including (a) noticing positive events, (b) savoring positive events, (c) identifying personal strengths, (d) behavioral activation to set and work toward attainable goals, (e) mindfulness, (f) positive reappraisal, (g) gratitude, and (h) acts of kindness. Outcome data were collected via online surveys at baseline, postintervention, and 1-month follow-up. Results: Completion rates (88%) and satisfaction ratings (10-point scale) were high (LARKSPUR: M = 9.14, standard deviation (SD) = 1.49; control: M = 8.59, SD = 1.97). Improvements were greater in LARKSPUR participants compared with control participants on measures of positive affect (Cohen's d = 0.19 [0.15, 0.24]), negative affect (Cohen's d = -0.07 [-0.11, -0.02]), and pain catastrophizing (Cohen's d = -0.14 [-0.23, -0.05]). Improvements in positive affect (Cohen's d = 0.17 [0.13, 0.22]) and negative affect (Cohen's d = -0.11 [-0.15, -0.06]) were maintained at 1-month follow-up. Dose-response analyses indicated that intervention engagement significantly predicted pre-to-post and post-to-follow-up reductions in pain catastrophizing. Discussion and implications: The current preliminary findings add to existing literature and highlight the specific potential of internet-delivered positive affect skills programs for adults with FMS. Clinical trial registration: NCT04869345.

Innovation in aging · 11 citationsread the source →

Outcomes of Early Liver Transplantation for Patients With Severe Alcoholic Hepatitis.

Background & aims: The American Consortium of Early Liver Transplantation for Alcoholic Hepatitis comprises 12 centers from 8 United Network for Organ Sharing regions studying early liver transplantation (LT) (without mandated period of sobriety) for patients with severe alcoholic hepatitis (AH). We analyzed the outcomes of these patients. Methods: We performed a retrospective study of consecutive patients with a diagnosis of severe AH and no prior diagnosis of liver disease or episodes of AH, who underwent LT before 6 months of abstinence from 2006 through 2017 at 12 centers. We collected data on baseline characteristics, psychosocial profiles, level of alcohol consumption before LT, disease course and treatment, and outcomes of LT. The interval of alcohol abstinence was defined as the time between last drink and the date of LT. The primary outcomes were survival and alcohol use after LT, defined as slip or sustained. Results: Among 147 patients with AH who received liver transplants, the median duration of abstinence before LT was 55 days; 54% received corticosteroids for AH and the patients had a median Lille score of 0.82 and a median Sodium Model for End-Stage Liver Disease score of 39. Cumulative patient survival percentages after LT were 94% at 1 year (95% confidence interval [CI], 89%-97%) and 84% at 3 years (95% CI, 75%-90%). Following hospital discharge after LT, 72% were abstinent, 18% had slips, and 11% had sustained alcohol use. The cumulative incidence of any alcohol use was 25% at 1 year (95% CI, 18%-34%) and 34% at 3 years (95% CI, 25%-44%) after LT. The cumulative incidence of sustained alcohol use was 10% at 1 year (95% CI, 6%-18%) and 17% at 3 years (95% CI, 10%-27%) after LT. In multivariable analysis, only younger age was associated with alcohol following LT (P = .01). Sustained alcohol use after LT was associated with increased risk of death (hazard ratio, 4.59; P = .01). Conclusions: In a retrospective analysis of 147 patients who underwent early LT (before 6 months of abstinence) for severe AH, we found that most patients survive for 1 year (94%) and 3 years (84%), similar to patients receiving liver transplants for other indications. Sustained alcohol use after LT was infrequent but associated with increased mortality. Our findings support the selective use of LT as a treatment for severe AH. Prospective studies are needed to optimize selection criteria, management of patients after LT, and long-term outcomes.

Gastroenterology · 270 citationsread the source →

Prevalence and Nature of Sexist and Racial/Ethnic Microaggressions Against Surgeons and Anesthesiologists.

Importance: Workplace mistreatment can manifest as microaggressions that cause chronic, severe distress. As physician burnout becomes a global crisis, quantitative research to delineate the impact of microaggressions is imperative. Objectives: To examine the prevalence and nature of sexist and racial/ethnic microaggressions against female and racial/ethnic-minority surgeons and anesthesiologists and assess the association with physician burnout. Design, setting, and participants: This cross-sectional survey evaluated microaggressions and physician burnout within a diverse cohort of surgeons and anesthesiologists in a large health maintenance organization. A total of 1643 eligible participants were sent a recruitment email on January 8, 2020, 1609 received the email, and 652 replied, for a response rate of 41%. The study survey remained open until February 20, 2020. A total of 588 individuals (37%) were included in the study after exclusion criteria were applied. Exposures: The Maslach Burnout Inventory, the Racial Microaggression Scale, and the Sexist Microaggression Experience and Stress Scale. Main outcomes and measures: The primary outcomes were prevalence and nature of sexist and racial/ethnic microaggressions against female and racial/ethnic-minority surgeons and anesthesiologists using the Sexist Microaggression Experience and Stress Scale and Racial Microaggression Scale. Secondary outcomes were frequency and severity of microaggressions, prevalence of physician burnout, and associations between microaggressions and physician burnout. Results: Data obtained from 588 respondents (249 [44%] female, 367 [62%] racial/ethnic minority, 224 [38.1%] 40-49 years of age) were analyzed. A total of 245 of 259 female respondents (94%) experienced sexist microaggressions, most commonly overhearing or seeing degrading female terms or images. Racial/ethnic microaggressions were experienced by 299 of 367 racial/ethnic-minority physicians (81%), most commonly reporting few leaders or coworkers of the same race/ethnicity. Criminality was rare (18 of 367 [5%]) but unique to and significantly higher for Hispanic and Black physicians. Individuals who identified as underrepresented minorities were more likely to experience environmental inequities (odds ratio [OR], 4.21; 95% CI, 1.6-10.75; P = .002) and criminality (OR, 14.93; 95% CI, 4.5-48.5; P < .001). The prevalence of physician burnout was 47% (280 of 588 physicians) and higher among female physicians (OR, 1.60; 95% CI, 1.03-2.47; P = .04) and racial/ethnic-minority physicians (OR, 2.08; 95% CI, 1.31-3.30; P = .002). Female physicians who experienced sexist microaggressions (racial/ethnic-minority female physicians: OR, 1.84; 95% CI, 1.04-3.25; P = .04; White female physicians: OR, 1.99; 95% CI, 1.07-3.69; P = .03) were more likely to experience burnout. Racial/ethnic-minority female physicians (OR, 1.86; 95% CI, 1.03-3.35; P = .04) who experienced racial microaggressions were more likely to report burnout. Racial/ethnic-minority female physicians who had the compound experience of sexist and racial/ethnic microaggressions (OR, 2.05; 95% CI, 1.14-3.69; P = .02) were more likely to experience burnout. Conclusions and relevance: The prevalence of sexist and racial/ethnic microaggressions against female and racial/ethnic-minority surgeons and anesthesiologists was high and associated with physician burnout. This study provides a valuable response to the increasing call for evidence-based data on surgical workplace mistreatment.

JAMA surgery · 99 citationsread the source →

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

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

The lancet. Psychiatry · 211 citationsread the source →

Prospective Study on Salivary Evening Melatonin and Sleep before and after Pinealectomy in Humans.

Melatonin is secreted systemically from the pineal gland maximally at night but is also produced locally in many tissues. Its chronobiological function is mainly exerted by pineal melatonin. It is a feedback regulator of the main circadian pacemaker in the hypothalamic suprachiasmatic nuclei and of many peripheral oscillators. Although exogenous melatonin is approved for circadian rhythm sleep disorders and old-age insomnia, research on endogenous melatonin in humans is hindered by the great interindividual variability of its amount and circadian rhythm. Single case studies on pinealectomized patients report on disrupted but also hypersomnic sleep. This is the first systematic prospective report on sleep with respect to pinealectomy due to pinealocytoma World Health Organization grade I without chemo- or radiotherapy. Before and after pinealectomy, 8 patients completed questionnaires on sleep quality and circadian rhythm (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Morningness-Eveningness Questionnaire), 2 nights of polysomnography, salivary evening melatonin profiles, and qualitative assessment of 2 weeks of actigraphy and sleep logs. Six patients were assessed retrospectively up to 4 years after pinealectomy. Before pinealectomy, all but 1 patient showed an evening melatonin rise typical for indifferent chronotypes. After pinealectomy, evening saliva melatonin was markedly diminished, mostly below the detection limit of the assay (0.09 pg/mL). No systematic change in subjective sleep quality or standard measures of polysomnography was found. Mean pre- and postoperative sleep efficiency was 94% and 95%, and mean sleep-onset latency was 21 and 17 min, respectively. Sleep-wake rhythm during normal daily life did not change. Retrospective patients had a reduced sleep efficiency (90%) and more stage changes, although this was not significantly different from prospective patients. In conclusion, melatonin does seem to have a modulatory, not a regulatory, effect on standard measures of sleep. Study output is limited by small sample size and because only evening melatonin profiles were assessed.

Journal of biological rhythms · 32 citationsread the source →

Cohort Profile: The National Longitudinal Study of Adolescent to Adult Health (Add Health)

The National Longitudinal Study of Adolescent Health (Add Health) was developed in the 1990s in response to a mandate from the United States Congress to fund a study of adolescent health, and was designed by a team of multidisciplinary investigators from the social, behavioural and biomedical sciences. The original purpose of Add Health was to understand the causes of adolescent health and health behaviour, with special emphasis on the multiple contexts of adolescent life. To achieve this scientific goal, Add Health sampled the school and family environments in which young people live their lives, which included data on peer relationship dyads, parents, siblings, neighbourhoods and communities, and provides independent and direct measurement of these complex environments over time. As the cohort transitioned into adulthood, research objectives turned to understanding how adolescent experiences, behaviours and contexts are linked to health and achievement outcomes in adulthood, and the name of the study was officially changed to The National Longitudinal Study of Adolescent to Adult Health in 2014. Add Health is housed at the Carolina Population Center at the University of North Carolina (UNC) and has been led by two principal investigators and project directors: J Richard Udry from 1994–2004; and Kathleen Mullan Harris from 2004 to the present. Add Health is a nationally representative cohort study of more than 20 000 adolescents in grades 7–12 (aged 12–19) in the USA in 1994–95, who have been followed through adolescence and into adulthood with five in-home interviews in 1995 (Wave I), 1996 (Wave II), 2001–02 (Wave III), 2008–09 (Wave IV) and 2016–18 (Wave V).1Figure 1 displays the sampling design for selecting the original cohort. A school-based design selected 80 high schools and a paired feeder school from a list of all high schools in the USA in 1994. An in-school questionnaire was administered to more than 90 000 students in grades 7–12, who attended these schools during the 1994–95 school year, and school administrators also filled out a questionnaire about the school. Sampling structure. School rosters from the 1993–94 school year provided the sampling frame for a second level of sampling for a 90-min in-home interview with an adolescent and a 30-min interview with one parent. A grade- and gender-stratified core sample was selected from each school pair, representing a self-weighting nationally representative sample of 12 105 American adolescents in grades 7–12 in 1995. Based on responses to the in-school survey, specific subpopulations were oversampled for purposes of providing sufficient numbers for research on vulnerable and otherwise rare populations, including ethnic (Cuban, Puerto Rican and Chinese), genetic relatedness to siblings (identical/fraternal twins, full/half siblings and unrelated adolescents living in the same household), adoption status and disability samples. Black adolescents with highly educated parents were also oversampled. For two large schools and fourteen small schools, interviews with all enrolled students were attempted to create a special saturation sample. The core sample plus the special samples yield a total of 20 745 adolescents. This Wave I in-home sample represents the national cohort of adolescents in grades 7–12 in the USA in 1995, which is followed prospectively. Because school rosters from the year preceding sample selection were used as the sampling frame for the prospective cohort, high school dropouts over 2 years (e.g. 1993–94; 1994–95) were eligible for sample selection, resulting in little bias due to high school dropouts.2 For more details on design, see Harris 2010 and Harris et al., 2013.3,4 Figure 2 shows the longitudinal design of Add Health. The Wave I in-home adolescent cohort has been followed up with four subsequent waves spanning 20+ years. In 1996, all adolescents in grades 7 through 11 in Wave I (plus 12th graders who were part of the genetic and adopted sample) were re-interviewed for Wave II (n = 14 738); the decision not to follow up the seniors who were in grade 12 at Wave I was design-based. The Wave II sample were in grades 8 through 12. A follow-up school administrator interview measured change in school context from 1995 to 1996. Longitudinal design. The original cohort was followed through their transition to early adulthood with a Wave III in-home interview in 2001–02 when the sample was aged 18–26 years (n = 15 197). A sample of 1507 partners were randomly selected during the in-home interview and interviewed, filling quota samples of about 500 married, 500 cohabiting and 500 dating partners. Wave IV re-interviewed the original cohort as they settled into young adulthood in 2008–09 when the cohort was aged 24–32 years (n = 15 701). Wave V followed the cohort to the end of young adulthood when they were aged 32–42, with continuous interviewing using a mixed-mode protocol during 2016–18. Finally, the Add Health Parent Study completed a 20-year follow-up of a subset of the parents of Add Health respondents during 2015–17 (n = 3006). Add Health uses state-of-the-art methods and techniques for panel maintenance and tracing to locate and schedule an interview with all living eligible respondents, including those who may have been non-responsive in a preceding wave. Table 1 presents response rates for the eligible sample at each completed wave of interviews. Response rates have been quite high, highest when the interval between interview waves is short but remarkably high even when the interval is over 5 years at Waves III and IV. The transition from adolescence to early adulthood and the young adult period is an especially transient phase of the life course and it is difficult to track and locate young people. Add Health has done exceptionally well, with response rates of 77.4% and 80.3% at Waves III and IV. Response rates in Add Health for the eligible sample at each wave of in-home interviews By design, respondents who were in the 12th grade at Wave I and who were not part of the genetic sample were not interviewed at Wave II. Response rate at Wave III is based on 15 170 respondents who had data at Wave I. An additional 27 respondents without Wave I data were included at Wave III as part of the genetic subsample. Wave V response rates are not provided because data collection is ongoing, and only a subset of Wave V respondents completed in-home interviews. Response rates in Add Health for the eligible sample at each wave of in-home interviews By design, respondents who were in the 12th grade at Wave I and who were not part of the genetic sample were not interviewed at Wave II. Response rate at Wave III is based on 15 170 respondents who had data at Wave I. An additional 27 respondents without Wave I data were included at Wave III as part of the genetic subsample. Wave V response rates are not provided because data collection is ongoing, and only a subset of Wave V respondents completed in-home interviews. There has been differential attrition by gender, age, socioeconomic status, urban residence, immigrant status and race across time, with higher response rates for female, younger, higher socioeconomic status, urban, native-born and White respondents at Waves III and IV. These attrition patterns are consistent with most longitudinal cohort studies. Add Health response rates exceed other national studies with multiple year intervals between waves (e.g. National Survey of Families and Households 2001–03 wave had a 55% response rate; Midlife in the United States 2004–06 interview had a 75% retention rate).5,6 At each wave, Add Health analysed whether patterns of attrition pose any bias to estimates of survey outcomes.7–10 In general, non-response analyses compare respondents and non-respondents on a range of demographic, health, behavioural and attitudinal indicators measured at baseline, and estimate the extent to which differences between respondents and non-respondents introduce bias in study results. Results indicated that total and relative biases, remaining after study estimates were adjusted with final sampling weights, were minimal and that the sample at each wave adequately represented the same population as the Wave I sample. Analysis of bias due to attrition at Wave IV indicated low rates of bias that rarely exceeded 1%, which is small relative to the 20% to 80% prevalence rates for most of the baseline indicators. Despite common patterns of attrition over time, the design strategy to re-interview the original Wave I cohort at each follow-up wave minimizes non-response bias and continues to adequately represent the original cohort of 7-12th graders in US schools in 1995. Add Health contains unprecedented environmental, behavioural, psychosocial, biological and genetic data from early adolescence into adulthood on a large, nationally representative sample with extensive racial, ethnic, socioeconomic and geographical diversity.4 Longitudinal survey data on respondents’ social, economic, psychological and physical well-being is combined with contextual data on family, neighbourhood, community, school, friendships, peer groups and romantic relationships, providing unique opportunities to study how psychological characteristics, social environments and behaviours beginning in early adolescence are linked to health and well-being in adulthood. Extensive longitudinal life histories of health-related behaviour are available, including physical activity, risk behaviour, substance use, sexual behaviour, civic engagement, education and multiple longitudinal indicators of health status, such as general health, chronic illness, overweight status and obesity, mental health, disability, health promotion and sleep. Objective measures of health were collected across all waves, including anthropometrics, sexually transmitted infection (STI) test results [including human immunodeficiency virus (HIV)], DNA and an expanded set of biomarkers in adulthood (Waves IV and V) (including blood pressure and pulse, measures of glucose homeostasis, lipid metabolism, inflammation, immune and renal function and a medications inventory). Below we describe the innovative multilevel data that have provided unprecedented research opportunities for a multidisciplinary scientific community. The clustered design of Add Health makes possible unique contextual levels of measurement, shown in Table 2. School-context data come from school administrator reports on school policies, health services and other school characteristics and from the in-school interviews of students whose aggregated responses represent school census measures. From respondent reports of colleges attended, college context data have been linked to individual records. Family-context data come from parent questionnaires, adolescent in-school and in-home questionnaires and interviews with siblings and additional adolescents living in the same household. Contextual levels of measurement in Add Health W1 = adolescent in- school and in-home, parent and school administrator surveys, geocodes. W2 = adolescent in-home, school administrator and geocodes. W3 = young adult in-home and partner sample surveys, geocodes, biomarkers. W4 = young adult in-home, biomarkers, geocodes. W5 = adult survey, biomarkers, geocodes. Additional variables from administrative datasets (e.g. US Census, Centers for Disease Control and Prevention, National Center for Health Statistics, Federal Bureau of Investigation, National Council of Churches, Common Core of Data, Private School Survey). , variable available; o, planned variable construction. Contextual levels of measurement in Add Health W1 = adolescent in- school and in-home, parent and school administrator surveys, geocodes. W2 = adolescent in-home, school administrator and geocodes. W3 = young adult in-home and partner sample surveys, geocodes, biomarkers. W4 = young adult in-home, biomarkers, geocodes. W5 = adult survey, biomarkers, geocodes. Additional variables from administrative datasets (e.g. US Census, Centers for Disease Control and Prevention, National Center for Health Statistics, Federal Bureau of Investigation, National Council of Churches, Common Core of Data, Private School Survey). , variable available; o, planned variable construction. Adolescents were asked to nominate friends and sexual and romantic partners from the school rosters in the in-school and in-home surveys at Waves I and II. Peer networks characteristics can be constructed by linking friends’ data and constructing variables based on friends’ responses, and similar measures can be constructed for linked romantic and sexual partners. These peer- and dyad-context measures constitute the social network data, including information on friendship networks, sexual networks and friendship and relationship dyads. Respondents’ home residences have been geocoded at each interview wave, and contextual data on the neighbourhood, community and state have been merged to all individual records. Nearly 12 000 environmental data elements at multiple geographical levels are available across waves. This includes such information as race, ethnic, foreign-born and religious denomination composition, poverty rates, crime statistics, STI prevalence, divorce and child support laws, welfare policies, cigarette taxes, the proximity and number of parks, sidewalks, recreation centres, fast food restaurants, alcohol outlets and other physical and social characteristics of the environments in which young people live. Table 3 shows the array of survey and biological data in Add Health. The top panel lists the domains covered by the survey instruments at each wave, including individual-level data on household and family structure, personality, religiosity and spirituality, relationships, sexual behaviour, contraception, pregnancy, children and parenting, sleep patterns, physical activity, diet, substance use/abuse, violence, delinquency, involvement with the criminal justice system, education history, work experiences, military service, chronic and disabling conditions, injury, mental health, suicide and health service access and use. Even though respondents were first interviewed in early adolescence, there are data on infancy (birthweight) and childhood (e.g. maltreatment, chronic conditions, attention deficit hyperactivity disorder) and complete data on fertility outcomes (there were more than 14 500 births to Add Health respondents by Wave IV). Survey and biomarker domains across Waves I-V in Add Health Survey and biomarker domains across Waves I-V in Add Health The bottom panel of Table 3 shows the biological measures available across waves. The original study design included important features for understanding biological processes in health and developmental trajectories across the life course, including an embedded genetic sample with more than 3000 pairs of adolescents with varying biological resemblance (see Figure 1) and measurement of height and weight to track the obesity epidemic. At Wave III, urine and saliva samples were collected to test for STI and HIV,11,12 and buccal cell saliva was collected from twins and full siblings in the genetic subsample for DNA extraction.13 An expanded set of biological measures were collected at Wave IV, including biomarkers of cardiovascular health (blood pressure, pulse), metabolic processes (waist circumference, glycosylated haemoglobin, blood glucose, lipids), immune function (Epstein-Barr virus), inflammation (C-reactive protein) and a medications inventory. Repeat biomarker measures were collected at Wave V, including new markers of renal disease. Saliva DNA was collected from the full sample at Wave IV. Candidate loci in the dopamine and serotonin pathways have been genotyped and disseminated to the scientific community.14 Genome-wide genotyping was completed on 10 974 Wave IV respondents who consented to archive their specimens for further testing, and genome-wide association study (GWAS) data are available from the database of Genotypes and Phenotypes (dbGaP). Add Health maintains a biospecimen archive available for ancillary studies. Add Health has a large and multidisciplinary user base of more than 50 000 researchers around the world, who have published over 3500 peer-reviewed articles in more than 750 different disciplinary journals, and has been the data source for more than 800 master’s theses and dissertations. Publications are listed at [https://www.cpc.unc.edu/projects/addhealth/publications]. Early publications focused on the role of social context in the development of adolescent health, behaviour, expectations and attainment, finding important influences of family and school connectedness,15 peer influence,16–18 romantic relationships,19 and neighbourhoods.20–22 For example, adolescents with a greater number and higher quality of connections to their school and family had better physical and mental health and higher attainment than youth with Adolescents whose friendship networks included friends with highly parents were than those whose friends had parents to studies that romantic in adolescence can adolescent and is with higher rates of obesity and weight in publications an of chronic young including a prevalence of and prevalence of the longitudinal data, researchers have the developmental and health pathways to young adult Add Health data support longitudinal studies of partner substance and health during the early life course from adolescence into young Add Health has the obesity and outcomes for adolescents. In adolescence of the sample were in 2001–02 when the cohort was aged the to in of the cohort at 24–32 was on these longitudinal data, The and the of obesity early in that adolescents were more to obesity in young adulthood with overweight by a risk of to individual obesity trajectories from adolescence at Wave II to young adulthood at Wave III into not who were who during the transition to young adulthood, and who were adolescence and young adulthood, As shown in Figure greater to obesity during adolescence and young adulthood is with a higher of high and sleep in adulthood. from adolescence to young adulthood with multiple health outcomes in adulthood (n The unique design and of the sample possible health research on special including the adopted youth living with parents sexual and adopted adolescents are more to suicide than their adolescents are at higher health risk on a range of indicators with adolescents who only one and more and than There is a large and of research that the genetic data with the longitudinal environmental data to the of and in health and behavioural of genetic research articles have these on a range of including risk substance sexual and friendship and Genome-wide association study (GWAS) data were for the pairs and Wave IV archive the of a large number of These the new differences in the education and of school environments in the education association with and family and education role in social and cohort differences in the genetic relationship between education and In innovative new research is providing human of genetic in which the of individual behaviour, for and Figure for social genetic of and friends on attainment, and The the of school and of for attainment in the top in the second panel and height in the The is the baseline of on outcomes in a with other and the represent the adjusted for individual-level The results that the of an and friends the attainment, an height is with the height of Add Health has in for new including attainment, height and alcohol genetic Add Health research uses biomarker data to social and behavioural with measures of research has the between a childhood and STI social status and and and life course of social and life for The role of social and social context in pathways was for the first young the for in the early in life and biological are to family and urban young from social is with mental health but physical health for young with The of Add Health from contextual and national design. The adolescent social context and peer network data, in are unique because they not on to an of an national of people who live in all 50 and come from race, ethnic, geographical and socioeconomic and ethnic with sufficient numbers to of Puerto and and and vulnerable including with children and adopted and sexual genetic sample of over 3000 pairs of with varying biological and longitudinal data from respondents and their longitudinal social, behavioural and biological data beginning in early adolescence and into extensive longitudinal multilevel data beginning in early adolescence on life and social and physical including family, school, neighbourhood, community and social measures of health including blood pressure, glucose, virus circumference, and and DNA on 000 and genome-wide genotyping on the full sample at Wave and collection of DNA on twins and full data be available in the including and data (see Table a of the of survey data measurement of specific and a for survey and biomarker measures. are available to researchers in representing a subset of and high which are only to which can only be used in a data to Add Health data to other and high school data, which are available in data access the and of respondents data access to a range of including data access study and can be at data can be Add Health is an longitudinal study of a nationally representative US cohort of 20 745 adolescents in grades (aged in includes four in-home interviews in 1996, 2016–18. attrition has been with response rates from to across follow-up waves, and attrition bias has been The study unprecedented environmental, behavioural, psychosocial, biological and genetic data from early adolescence into adulthood with extensive racial, ethnic, socioeconomic and geographical Add Health has a large, multidisciplinary user base of over 50 000 researchers around the world, who have published over 3500 research the Add Health cohort at the of the obesity with for health and social genetic of and on health and Add Health datasets are to a data to the of information and in of the see Add Health is by the National of Health and with from other and The full list of can be at This research uses data from Add a project by Kathleen Mullan Harris and designed by J Richard and Kathleen Mullan at the University of North Carolina at and by from the National of Health and with from other and is due to and for in the original design. also to data from National of Health and to Kathleen Mullan Harris and to Kathleen Mullan and of

International Journal of Epidemiology · 531 citationsread the source →

Adherence to Once-daily and Twice-daily Direct-acting Antiviral Therapy for Hepatitis C Infection Among People With Recent Injection Drug Use or Current Opioid Agonist Therapy.

Background: This study investigated adherence and associated factors among people with recent injection drug use (IDU) or current opioid agonist therapy (OAT) and compared once-daily to twice-daily hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy. Methods: SIMPLIFY and D3FEAT are international, multicenter studies that recruited participants with recent IDU (previous 6 months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in 8 countries. Participants received sofosbuvir/velpatasvir (once daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice daily) ± ribavirin (D3FEAT) for 12 weeks administered in electronic blister packs. We evaluated overall adherence (proportion of prescribed doses taken) and nonadherence (<90% adherent) between dosing patterns. Results: Of 190 participants, 184 (97%) completed treatment. Median adherence was 92%, with higher adherence among those receiving once-daily vs twice-daily therapy (94% vs 87%, P = .005). Overall, 40% of participants (n = 76) were nonadherent (<90% adherent). Recent stimulant injecting (odds ratio [OR], 2.48 [95% confidence interval {CI}, 1.28-4.82]), unstable housing (OR, 2.18 [95% CI, 1.01-4.70]), and twice-daily dosing (OR, 2.81 [95% CI, 1.47-5.36]) were associated with nonadherence. Adherence decreased during therapy. Sustained virologic response was high in nonadherent (89%) and adherent populations (95%, P = .174), with no difference in SVR between those who did and did not miss 7 consecutive doses (92% vs 93%, P = .897). Conclusions: This study demonstrated high adherence to once- and twice-daily DAA therapy among people with recent IDU or currently receiving OAT. Nonadherence described did not impact treatment outcomes, suggesting forgiveness to nonadherence.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 59 citationsread the source →

No pain, no gain: an exploratory within-subjects mixed-methods evaluation of the patient experience of sleep restriction therapy (SRT) for insomnia.

Objective: To explore the patient experience of Sleep Restriction Therapy (SRT) for insomnia, with particular focus on elucidating possible side-effects, challenges to adherence and implementation and perceptions of benefit/impact. Methods: To fully investigate the patient experience of sleep restriction therapy for insomnia we designed a within-subjects mixed-method study, employing sleep and daytime functioning questionnaires, assessments of sleep-restriction-related side-effects, prospective qualitative audio-diaries and post-treatment semi-structured interviews. University of Glasgow Sleep Centre. Eighteen patients with Primary Insomnia (mean age=42; range 18-64). Patients took part in a 4-week brief sleep restriction intervention, involving two group sessions and two subsequent follow-up phone calls in the home environment. Measurements and results: Sleep diaries and global measures of insomnia severity and sleep quality, as expected, demonstrated robust improvements at both post-treatment and 3-month follow-up (all large effect sizes). Daytime functioning/health-related quality of life variables similarly evidenced strong treatment effects (moderate to large effect sizes). Reported side-effects were common, with ≥50% of patients reporting impairment in 8 out of 12 listed symptoms as a consequence of initiating treatment. The four most common side-effects were 'fatigue/exhaustion' (100%), 'extreme sleepiness' (94%), 'reduced motivation/energy' (89%) and 'headache/migraine' (72%) [Mean number of symptoms per patient=7.2 (2.4); range 3-11]. Intriguingly, both side-effect frequency and ratings of side-effect interference were associated with baseline to post-treatment improvements in sleep quality. Qualitative real-time audio-diaries during week 1 of treatment and post-treatment interviews provided rich accounts of side-effects associated with acute SRT implementation; general challenges surrounding treatment implementation and adherence/non-adherence; and modifications to sleep parameters, daytime functioning and perceptions of sleep/sleep period. Conclusions: This work has important implications for the delivery of SRT, particularly concerning awareness of possible 'adverse events' and likely implementation/adherence challenges. Findings also pave the way for testable hypotheses concerning possible mechanisms of action involved in sleep restriction treatment.

Sleep medicine · 139 citationsread the source →