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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 →

A community-based, multi-level, multi-setting, multi-component intervention to reduce weight gain among low socioeconomic status Latinx children with overweight or obesity: The Stanford GOALS randomised controlled trial.

Background: There are few long-term studies of interventions to reduce in low socioeconomic status children with overweight or obesity. The Stanford GOALS trial evaluated a 3-year, community-based, multi-level, multi-setting, multi-component (MMM) systems intervention, to reduce weight gain among low socioeconomic status, Latinx children with overweight or obesity. Methods: We did a two-arm, parallel group, randomised, open-label, active placebo-controlled trial with masked assessment over 3 years. Families from low-income, primarily Latinx communities in Northern California, CA, USA, with 7-11-year-old children with overweight or obesity were randomly assigned to a MMM intervention or a Health Education (HE) comparison intervention. The MMM intervention included home environment changes and behavioural counselling, community after school team sports, and reports to primary health-care providers. The primary outcome was child BMI trajectory over three years. Secondary outcomes included one- and two-year changes in BMI. This trial is registered with ClinicalTrials.govNCT01642836. Findings: Between July 13, 2012, and Oct 3, 2013, 241 families were recruited and randomly assigned to MMM (n=120) or HE (n=121). Children's mean age was 9·5 (SD 1·4) years, 134 (56%) were female and 107 (44%) were male, and 236 (98%) were Latinx. 238 (99%) children participated in year 1, 233 (97%) in year 2, and 227 (94%) in year 3 of follow-up assessments. In intention-to-treat analysis, over 3 years, the difference between intervention groups in BMI trajectory was not significant (mean adjusted difference -0·25 [95% CI -0·90 to 0·40] kg/m2; Cohen's d=0.10; p=0·45). Children in the MMM intervention group gained less BMI over 1 year than did children in the HE intervention group (-0·73 [-1·07 to -0·39] kg/m2, d=0.55); the same was true over 2 years (-0·63 [-1·13 to -0·14] kg/m2; d =0.33). No differential adverse events were observed. Interpretation: The MMM intervention did not reduce BMI gain versus HE over 3 years but the effects over 1 and 2 years in this rigorous trial show the promise of this systems intervention approach for reducing weight gain and cardiometabolic risk factors in low socioeconomic status communities. Funding: US National Institutes of Health.

The lancet. Diabetes & endocrinology · randomised controlled trial · 33 citationsread the source →

Sweet-tasting solutions for needle-related procedural pain in infants one month to one year of age.

Background: Administration of oral sucrose or glucose with and without non-nutritive sucking is frequently used as a non-pharmacological intervention for needle-related procedural pain relief in infants. Objectives: To determine the effectiveness of sweet-tasting solutions for needle-related procedural pain in infants one month to one year of age compared with no treatment, placebo, other sweet-tasting solutions, or pharmacological or other non-pharmacological pain-relieving methods. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012); MEDLINE via Ovid (1966 to 2012); CINAHL via OVID (1982 to 2012). The World Health Organization International Clinical Trials Registry Platform was also searched for any ongoing trials. Clinical trial registries, conference proceedings and references for randomised controlled trials (RCTs) were also searched. An updated search was run to capture any new publications before finalising the review in April 2012 and no new included studies were identified. Two review authors (MK & JF) independently abstracted data and assessed quality using a standard form. Authors have been contacted for missing data. Selection criteria: Randomised-controlled trials using a sweet-tasting solution to treat pain in healthy term infants (gestational age 37 weeks and over), between one month and 12 months of age who required needle-related procedures. These procedures included but were not limited to: subcutaneous or intramuscular injections, venepuncture, and heel lance. Studies in which the painful procedure was circumcision, lumbar puncture or supra-pubic bladder aspiration were not included as they are more severe and painful than needle-related procedures. Control conditions included no treatment or placebo (water) or any other identical intervention (same appearance and consistency) without active ingredient, another sweet-tasting solution, a pharmacological pain-relieving method (e.g. paracetamol, topical anaesthetic cream), non-pharmacological pain-relieving method (e.g. distraction method, non-nutritive sucking). Data collection and analysis: Assessment of trial quality, data extraction and synthesis of data were performed using standard methods of the Cochrane Pain, Palliative and Supportive Care Group. We report mean differences (MD) with 95% confidence intervals (CI) using fixed-effect models as appropriate for continuous outcome measures. We planned to report risk ratio (RR) and risk difference (RD) for dichotomous outcomes. The Chi(2) test and I(2) statistic were used to assess between-study heterogeneity. Main results: Sixty-five (65) studies were identified for possible inclusion in this review. Fourteen published RCTs with a total of 1551 participants met the inclusion criteria. Duration of cry was significantly reduced in infants who were administered a sweet-tasting solution [MD -13.47 (95% CI -16.80 to -10.15)], P < 0.00001 compared with water. However, there was considerable heterogeneity between the studies (I(2) = 94%) that we were unable to explain. Meta-analysis was not able to be undertaken for any of the other outcome measures, except for cry duration, because of differences in study design. However, most of the individual studies that measured pain found sucrose to significantly reduce pain compared with the control group. One study compared sucrose and Lidocaine-prilocaine cream and no significant difference was found between the two treatments for the outcomes pain and cry duration. Due to the differences between the studies, we were unable to identify the optimal concentration, volume or method of administration of sweet-tasting solutions in infants aged one to 12 months. Further large RCTs are needed. Authors' conclusions: There is insufficient evidence to confidently judge the effectiveness of sweet-tasting solutions in reducing needle-related pain in infants (one month to 12 months of age). The treatments do, however, appear promising. Data from a series of individual trials are promising, as are the results from a subset meta-analysis of studies measuring duration of crying. Further well controlled RCTs are warranted in this population to determine the optimal concentration, volume, method of administration, and possible adverse effects.

The Cochrane database of systematic reviews · meta-analysis · 26 citationsread the source →

Randomised trial of coconut oil, olive oil or butter on blood lipids and other cardiovascular risk factors in healthy men and women.

Introduction: High dietary saturated fat intake is associated with higher blood concentrations of low-density lipoprotein cholesterol (LDL-C), an established risk factor for coronary heart disease. However, there is increasing interest in whether various dietary oils or fats with different fatty acid profiles such as extra virgin coconut oil may have different metabolic effects but trials have reported inconsistent results. We aimed to compare changes in blood lipid profile, weight, fat distribution and metabolic markers after four weeks consumption of 50 g daily of one of three different dietary fats, extra virgin coconut oil, butter or extra virgin olive oil, in healthy men and women in the general population. Design: Randomised clinical trial conducted over June and July 2017. Setting: General community in Cambridgeshire, UK. Participants: Volunteer adults were recruited by the British Broadcasting Corporation through their websites. Eligibility criteria were men and women aged 50-75 years, with no known history of cancer, cardiovascular disease or diabetes, not on lipid lowering medication, no contraindications to a high-fat diet and willingness to be randomised to consume one of the three dietary fats for 4 weeks. Of 160 individuals initially expressing an interest and assessed for eligibility, 96 were randomised to one of three interventions; 2 individuals subsequently withdrew and 94 men and women attended a baseline assessment. Their mean age was 60 years, 67% were women and 98% were European Caucasian. Of these, 91 men and women attended a follow-up assessment 4 weeks later. Intervention: Participants were randomised to extra virgin coconut oil, extra virgin olive oil or unsalted butter and asked to consume 50 g daily of one of these fats for 4 weeks, which they could incorporate into their usual diet or consume as a supplement. Main outcomes and measures: The primary outcome was change in serum LDL-C; secondary outcomes were change in total and high-density lipoprotein cholesterol (TC and HDL-C), TC/HDL-C ratio and non-HDL-C; change in weight, body mass index (BMI), waist circumference, per cent body fat, systolic and diastolic blood pressure, fasting plasma glucose and C reactive protein. Results: LDL-C concentrations were significantly increased on butter compared with coconut oil (+0.42, 95% CI 0.19 to 0.65 mmol/L, P<0.0001) and with olive oil (+0.38, 95% CI 0.16 to 0.60 mmol/L, P<0.0001), with no differences in change of LDL-C in coconut oil compared with olive oil (-0.04, 95% CI -0.27 to 0.19 mmol/L, P=0.74). Coconut oil significantly increased HDL-C compared with butter (+0.18, 95% CI 0.06 to 0.30 mmol/L) or olive oil (+0.16, 95% CI 0.03 to 0.28 mmol/L). Butter significantly increased TC/HDL-C ratio and non-HDL-C compared with coconut oil but coconut oil did not significantly differ from olive oil for TC/HDL-C and non-HDL-C. There were no significant differences in changes in weight, BMI, central adiposity, fasting blood glucose, systolic or diastolic blood pressure among any of the three intervention groups. Conclusions and relevance: Two different dietary fats (butter and coconut oil) which are predominantly saturated fats, appear to have different effects on blood lipids compared with olive oil, a predominantly monounsaturated fat with coconut oil more comparable to olive oil with respect to LDL-C. The effects of different dietary fats on lipid profiles, metabolic markers and health outcomes may vary not just according to the general classification of their main component fatty acids as saturated or unsaturated but possibly according to different profiles in individual fatty acids, processing methods as well as the foods in which they are consumed or dietary patterns. These findings do not alter current dietary recommendations to reduce saturated fat intake in general but highlight the need for further elucidation of the more nuanced relationships between different dietary fats and health. Trial registration number: NCT03105947; Results.

BMJ open · randomised controlled trial · 118 citationsread the source →

A randomised controlled multicentre trial of treatments for adolescent anorexia nervosa including assessment of cost-effectiveness and patient acceptability - the TOuCAN trial.

Objective: To evaluate the clinical effectiveness and cost-effectiveness of inpatient compared with outpatient treatment and general (routine) treatment in Child and Adolescent Mental Health Services (CAMHS) against specialist treatment for young people with anorexia nervosa. In addition, to determine young people's and their carers' satisfaction with these treatments. Design: A population-based, pragmatic randomised controlled trial (RCT) was carried out on young people age 12 to 18 presenting to community CAMHS with anorexia nervosa. Setting: Thirty-five English CAMHS in the north-west of England co-ordinated through specialist centres in Manchester and Liverpool. Participants: Two hundred and fifteen young people (199 female) were identified, of whom 167 (mean age 14 years 11 months) were randomised and 48 were followed up as a preference group. Interventions: Randomised patients were allocated to either inpatient treatment in one of four units with considerable experience in the treatment of anorexia nervosa, a specialist outpatient programme delivered in one of two centres, or treatment as usual in general community CAMHS. The outpatient programmes spanned 6 months of treatment. The length of inpatient treatment was determined on a case-by-case basis on clinical need with outpatient follow-up to a minimum of 6 months. Main outcome measures: Follow-up assessments were carried out at 1, 2 and 5 years. The primary outcome measure was the Morgan-Russell Average Outcome Scale (MRAOS) and associated categorical outcomes. Secondary outcome measures included physical measures of weight, height, body mass index (BMI) and % weight for height. Research ratings included the Health of the National Outcome Scale for Children and Adolescents (HoNOSCA). Self report measures comprised the user version of HoNOSCA (HoNOSCA-SR), the Eating Disorder Inventory 2 (EDI-2), the Family Assessment Device (FAD) and the recent Mood and Feelings Questionnaire (MFQ). Information on resource use was collected in interview at 1, 2 and 5 years using the Child and Adolescent Service Use Schedule (CA-SUS). Satisfaction was measured quantitatively using a questionnaire designed for the study and qualitative (free) responses on it. The questionnaire data were supplemented by qualitative analysis of user and carer focus groups. Results: Of the 167 patients randomised, 65% adhered to the allocated treatment. Adherence was lower for inpatient treatment (49%) than for general CAMHS (71%) or specialist outpatient treatment (77%) (p = 0.013). Every subject was traced at both 1 and 2 years, with the main outcome measure completed (through contact with the subject, family members or clinicians), by 94% at 1 year, 93% at 2 years, but only 47% at 5 years. A validated outcome category was assigned for 98% at 1 year, 96% at 2 years and 60% at 5 years. There was significant improvement in all groups at each time point, with the number achieving a good outcome being 19% at 1 year, 33% at 2 years and 64% (of those followed up) at 5 years. Analysis demonstrated no difference in treatment effectiveness of randomisation to inpatient compared with outpatient treatment, or, specialist over generalist treatment at any time point, when baseline characteristics were taken into account. Generalist CAMHS treatment was slightly more expensive over the first 2 years of the study, largely because greater numbers were subsequently admitted to hospital after the initial treatment phase. The specialist outpatient programme was the dominant treatment in terms of incremental cost-effectiveness. Specialist treatments had a higher probability of being more cost-effective than generalist treatments and outpatient treatment had a higher probability of being more cost-effective than inpatient care. Parental satisfaction with treatment was generally good, though better with specialist than generalist treatment. Young people's satisfaction was much more mixed, but again better with specialist treatment, including inpatient care. Conclusion: Poor adherence to randomisation (despite initial consent to it), limits the assessment of the treatment effect of inpatient care. However, this study provides little support for lengthy inpatient psychiatric treatment on clinical or health economic grounds. These findings are broadly consistent with existing guidelines on the treatment of anorexia nervosa, which suggest that outpatient treatments should be offered to the majority, with inpatient treatment offered in rare cases, though our findings lend little support to a stepped-care approach in which inpatient care is offered to outpatient non-responders. Outpatient care, supported by brief (medical) inpatient management for correction of acute complications may be a preferable approach. The health economic analysis and user views both support NICE guidelines, which suggest that anorexia nervosa should be managed in specialist services that have experience and expertise in its management. Comprehensive general CAMHS might, however, be well placed to manage milder cases. Further research should focus on the specific components of outpatient psychological therapies. Although family-based treatments are well established, trials have not established their effectiveness compared with good-quality individual psychological therapies and the combination of individual and family approaches is untested. Further research is needed to establish which patients (if any) might respond to inpatient psychiatric treatment when unresponsive to outpatient care, the positive and negative components of it and the optimum length of stay. Trial registration: NRR number (National Research Register) N0484056615; Current Controlled Trials ISRCTN39345394.

Health technology assessment (Winchester, England) · randomised controlled trial · 56 citationsread the source →

Overweight and obesity in a representative sample of schoolchildren - exploring the urban-rural gradient in Sweden.

To present the prevalence and urban-rural differences of overweight and obesity in 7-9-year-old Swedish schoolchildren, we used anthropometric data from a nationally representative survey performed in 2008. Trained staff weighed and measured 4538 children in grades 1 and 2 in 94 primary schools. Weight classification was performed using the IOTF reference and school areas were classified based on level of urbanization and area-level education. Overweight was found in 17% of the children including 3% obese. For overweight, odds-ratios were 1.33 and 1.61 (significant) in semi-urban and rural areas, relative to urban areas. After adjusting for area-level education, differences by degree of urbanisation were greatly attenuated and non-significant. For obesity urban-rural differences were observed in boys only and remained after adjustment for area-level education. For area-level education, risk estimates were significantly elevated and unaffected by urbanization and gender, odds-ratios 1.75 and 2.21 for overweight and 2.62 and 3.69 for obesity, in medium- and low-education areas compared to high-education areas. This supports earlier reports identifying areas with low socioeconomic status as high-risk areas for overweight and obesity. However, this study also suggests that gender should be considered when targeting children in urban as well as rural communities for health promoting interventions.

Obesity reviews : an official journal of the International Association for the Study of Obesity · cohort or longitudinal · 85 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 →

Effect of Inpatient Palliative Care on Quality of Life 2 Weeks After Hematopoietic Stem Cell Transplantation: A Randomized Clinical Trial.

Importance: During hospitalization for hematopoietic stem cell transplantation (HCT), patients receive high-dose chemotherapy before transplantation and experience significant physical and psychological symptoms and poor quality of life (QOL). Objective: To assess the effect of inpatient palliative care on patient- and caregiver-reported outcomes during hospitalization for HCT and 3 months after transplantation. Design, setting, and participants: Nonblinded randomized clinical trial among 160 adults with hematologic malignancies undergoing autologous/allogeneic HCT and their caregivers (n = 94). The study was conducted from August 2014 to January 2016 in a Boston hospital; follow-up was completed in May 2016. Interventions: Patients assigned to the intervention (n=81) were seen by palliative care clinicians at least twice a week during HCT hospitalization; the palliative intervention was focused on management of physical and psychological symptoms. Patients assigned to standard transplant care (n=79) could be seen by palliative care clinicians on request. Main outcomes and measures: Primary: change in patient QOL from baseline to week 2; secondary: patient-assessed mood, fatigue, and symptom burden scores at baseline, 2 weeks, and 3 months after HCT and caregiver-assessed QOL and mood at baseline and 2 weeks after HCT. Results: Among 160 enrolled patients (mean age, 60 [SD, 13.3] years; 91 women [56.9%]; median hospital stay, 21 days) and 94 caregivers, 157 (98.1%) and 89 (94.7%), respectively, completed 2-week follow-up, and 149 patients (93.1%) completed 3-month follow-up. Patients in the intervention group reported a smaller decrease in QOL from baseline to week 2 (mean baseline score, 110.26; week 2 score, 95.46; mean change, -14.72) compared with patients in the control group (mean baseline score, 106.83; week 2 score, 85.42; mean change, -21.54; difference between groups, -6.82; 95% CI, -13.48 to -0.16; P = .045). Among the secondary outcomes, from baseline to week 2, patients in the intervention group vs those in the control group had less increase in depression (mean, 2.43 vs 3.94; mean difference, 1.52; 95% CI, 0.23-2.81; P = .02), lower anxiety (mean, -0.80 vs 1.12; mean difference, 1.92; 95% CI, 0.83-3.01; P < .001), no difference in fatigue (mean, -10.30 vs -13.65; mean difference, -3.34; 95% CI, -7.25 to 0.56; P = .09), and less increase in symptom burden (mean, 17.35 vs 23.14; mean difference, 5.80; 95% CI, 0.49-11.10; P = .03). At 3 months after HCT, intervention patients vs control patients had higher QOL scores (mean, 112.00 vs 106.66; mean difference, 5.34; 95% CI, 0.04-10.65; P = .048) and less depression symptoms (mean, 3.49 vs 5.19; mean difference, -1.70; 95% CI, -2.75 to -0.65; P = .002) but no significant differences in anxiety, fatigue, or symptom burden. From baseline to week 2 after HCT, caregivers of patients in the intervention group vs caregivers of patients in the control group reported no significant differences in QOL or anxiety but had a smaller increase in depression (mean, 0.25 vs 1.80; mean difference, 1.55; 95% CI, 0.14-2.96; P = .03). Conclusions and relevance: Among adults at a single institution undergoing HCT for hematologic malignancy, the use of inpatient palliative care compared with standard transplant care resulted in a smaller decrease in QOL 2 weeks after transplantation. Further research is needed for replication and to assess longer-term outcomes and cost implications. Trial registration: clinicaltrials.gov Identifier: NCT02207322.

JAMA · randomised controlled trial · 309 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 →

The validity of the brief version of the Fear of Negative Evaluation Scale.

The Fear of Negative Evaluation Scale [FNE; J. Consult. Clin. Psychol. 33 (1969) 448] is a commonly used measure of social anxiety. A brief version of the scale (FNEB) is available for convenient administration. Despite being widely advocated for use, the psychometric properties of the FNEB have not been evaluated with clinically anxious samples. The present study addressed the reliability and validity of the FNEB in a clinical sample of individuals with either social phobia (n = 82) or panic disorder (n = 99) presenting for treatment. Factor analysis supported the construct validity of the FNEB. The validity of the FNEB was further demonstrated through significant correlations with social avoidance and depression, and non-significant correlations with agoraphobic avoidance and demographic variables. The scale obtained excellent inter-item reliability (alpha = .97) and 2-week test-retest reliability (r = .94). Discriminant function analysis also supported validity of the FNEB. For example, individuals with social phobia scored significantly higher on the FNEB than those with panic disorder and a group of non-psychiatric community controls (n = 30). The FNEB was sensitive to pre- to post-CBT changes in both social anxiety and panic disorder, and changes on the FNEB correlated significantly with other measures of treatment responsiveness, such as reductions in somatic arousal, depression and other anxiety symptomatology. These research findings strongly support the validity of the FNEB and its clinical utility as an outcome measure in social anxiety treatment.

Journal of anxiety disorders · cohort or longitudinal · 114 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 →

Effects of Initiating Moderate Alcohol Intake on Cardiometabolic Risk in Adults With Type 2 Diabetes: A 2-Year Randomized, Controlled Trial.

Background: Recommendations for moderate alcohol consumption remain controversial, particularly in type 2 diabetes mellitus (T2DM). Long-term randomized, controlled trials (RCTs) are lacking. Objective: To assess cardiometabolic effects of initiating moderate alcohol intake in persons with T2DM and whether the type of wine matters. Design: 2-year RCT (CASCADE [CArdiovaSCulAr Diabetes & Ethanol] trial). (ClinicalTrials.gov: NCT00784433). Setting: Ben-Gurion University of the Negev-Soroka Medical Center and Nuclear Research Center Negev, Israel. Patients: Alcohol-abstaining adults with well-controlled T2DM. Intervention: Patients were randomly assigned to 150 mL of mineral water, white wine, or red wine with dinner for 2 years. Wines and mineral water were provided. All groups followed a Mediterranean diet without caloric restriction. Measurements: Primary outcomes were lipid and glycemic control profiles. Genetic measurements were done, and patients were followed for blood pressure, liver biomarkers, medication use, symptoms, and quality of life. Results: Of the 224 patients who were randomly assigned, 94% had follow-up data at 1 year and 87% at 2 years. In addition to the changes in the water group (Mediterranean diet only), red wine significantly increased high-density lipoprotein cholesterol (HDL-C) level by 0.05 mmol/L (2.0 mg/dL) (95% CI, 0.04 to 0.06 mmol/L [1.6 to 2.2 mg/dL]; P < 0.001) and apolipoprotein(a)1 level by 0.03 g/L (CI, 0.01 to 0.06 g/L; P = 0.05) and decreased the total cholesterol-HDL-C ratio by 0.27 (CI, -0.52 to -0.01; P = 0.039). Only slow ethanol metabolizers (alcohol dehydrogenase alleles [ADH1B*1] carriers) significantly benefited from the effect of both wines on glycemic control (fasting plasma glucose, homeostatic model assessment of insulin resistance, and hemoglobin A1c) compared with fast ethanol metabolizers (persons homozygous for ADH1B*2). Across the 3 groups, no material differences were identified in blood pressure, adiposity, liver function, drug therapy, symptoms, or quality of life, except that sleep quality improved in both wine groups compared with the water group (P = 0.040). Overall, compared with the changes in the water group, red wine further reduced the number of components of the metabolic syndrome by 0.34 (CI, -0.68 to -0.001; P = 0.049). Limitation: Participants were not blinded to treatment allocation. Conclusion: This long-term RCT suggests that initiating moderate wine intake, especially red wine, among well-controlled diabetics as part of a healthy diet is apparently safe and modestly decreases cardiometabolic risk. The genetic interactions suggest that ethanol plays an important role in glucose metabolism, and red wine's effects also involve nonalcoholic constituents. Primary funding source: European Foundation for the Study of Diabetes.

Annals of internal medicine · randomised controlled trial · 131 citationsread the source →

The assessment of cognitive-behavioral therapy skills in patients diagnosed with health anxiety: Development and pilot study on an observer-based rating scale.

Cognitive-behavioral therapy is a highly effective treatment of health anxiety, but it remains unclear through which mechanisms treatment effects prevail. Some evidence suggests that patients acquire skills-understood as techniques helping them reach therapy goals-through psychotherapy. In the current study, an observer-based rating scale for the skills assessment of patients with health anxiety (SAPH) was developed and validated in a pilot study. Based on 177 videotapes, four independent raters evaluated the frequency of skills acquired during cognitive and exposure therapy among 66 patients diagnosed with health anxiety with the SAPH. Predictive validity was evaluated by the Yale-Brown Obsessive-Compulsive Scale for Hypochondriasis. The SAPH demonstrated good interrater reliability (ICC(1,2)  = .88, p < .001, 95% CI [.81, .92]) and internal consistency (α = .94). Although patient skills did not significantly increase during three sessions, they significantly predicted a reduction in health anxiety symptoms at the end of treatment (R2  = .35). Patients' skills are highly important within the treatment of health anxiety. By providing external ratings of patients' skills with good psychometric properties, our pilot data suggest that the SAPH may complement current tools for the assessment of skills, specifically in targeting health anxiety.

Clinical psychology & psychotherapy · randomised controlled trial · 1 citationsread the source →

Self-compassion, physical health, and health behaviour: a meta-analysis.

This meta-analysis investigated relationships between self-compassion and (1) physical health and (2) health-promoting behaviour in a large pooled sample (N = 29,588) sourced from 94 peer-reviewed articles. As hypothesised, omnibus analyses revealed positive associations between self-compassion and both physical health (r = .18) and health behaviour (r = .26). Moderation analyses using 290 effects found that both associations varied according to health domain, participant age, intervention duration, and self-compassion measure. Self-compassion predicted outcomes in most health domains, with the strongest effects observed on global physical health, functional immunity, composite health behaviour, sleep, and danger avoidance. It did not predict frailty, maladaptive bodily routines, and substance abuse. Multi-session interventions designed to boost self-compassion predicted increased physical health and health behaviour, thereby supporting causal links between self-compassion and health outcomes. The effects of single-session inductions were non-significant. The mean effect of self-compassion on physical health was non-significant for young participants (12.00-19.99) and its effect on health behaviour was weakest among older participants (40.00+). Results support the proposition that self-compassion can promote better physical health. Practical implications of these findings are discussed.

Health psychology review · meta-analysis · 80 citationsread the source →

Perfectionism, Prolonged Stress Reactivity, and Depression: A Two-Wave Cross-Lagged Analysis.

Perfectionism is a vulnerability factor for a wide array of psychopathology. Despite much evidence suggesting dysregulated stress response as an intermediary process that links perfectionism to psychopathology, the lack of a cross-lagged examination deterred researchers from making causal interpretations. This study examined the directionality of effects among perfectionism dimensions, stress reactivity, and depression. A total of 189 participants at time 1 and 94 at time 2 completed an online survey that consisted of measures of perfectionism, stress reactivity, and depression, one month apart. Cross-lagged analysis results showed that personal standards perfectionism predicted later prolonged stress reactivity but not depression at time 2. Self-critical perfectionism predicted later depression but not prolonged stress reactivity at time 2. Rather, prolonged stress reactivity at time 1 predicted self-critical perfectionism at time 2. Findings suggest that perfectionism dimensions are distinct in creating a dysregulated stress process. Future studies could incorporate other stress-related variables (e.g., coping) to further explicate the stress-generation process, in conjunction with stress reactivity.

Journal of rational-emotive and cognitive-behavior therapy : RET · 6 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 →

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 →

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 →

SARS-CoV-2 in Spanish Intensive Care Units: Early experience with 15-day survival in Vitoria.

Purpose: Community transmission of SARS-CoV-2 was detected in Spain in February 2020, with 216% intensive care unit (ICU) capacity expanded in Vitoria by March 18th, 2020. Methods: We identified patients from the two public hospitals in Vitoria who were admitted to ICU with confirmed infection by SARS-CoV-2. Data reported here were available in April 6th, 2020. Mortality was assessed in those who completed 15-days of ICU stay. Results: We identified 48 patients (27 males) with confirmed SARS-CoV-2. Median [interquartile range (IQR)] age of patients was 63 [51-75] years. Symptoms began a median of 7 [5-12] days before ICU admission. The most common comorbidities identified were obesity (48%), arterial hypertension (44%) and chronic lung disease (37%). All patients were admitted by hypoxemic respiratory failure and none received non-invasive mechanical ventilation. Forty-five (94%) underwent intubation, 3 (6%) high flow nasal therapy (HFNT), 1 (2%) extracorporeal membrane oxygenation (ECMO) and 22 (46%) required prone position. After 15 days, 14/45 (31%) intubated patients died (13% within one week), 10/45 (22%) were extubated, and 21/45 (47%) underwent mechanical ventilation. Six patients had documented super-infection. Procalcitonin plasma above 0.5μg/L was associated with 16% vs. 19% (p=0.78) risk of death after 7 days. Conclusion: This early experience with SARS-CoV-2 in Spain suggests that a strategy of right oxygenation avoiding non-invasive mechanical ventilation was life-saving. Seven-day mortality in SARS-CoV-2 requiring intubation was lower than 15%, with 80% of patients still requiring mechanical ventilation. After 15 days of ICU admission, half of patients remained intubated, whereas one third died.

Anaesthesia, critical care & pain medicine · cohort or longitudinal · 156 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 →

Processing mode during repetitive thinking in socially anxious individuals: evidence for a maladaptive experiential mode.

Background and objectives: Evidence from the depression literature suggests that an analytical processing mode adopted during repetitive thinking leads to maladaptive outcomes relative to an experiential processing mode. To date, in socially anxious individuals, the impact of processing mode during repetitive thinking related to an actual social-evaluative situation has not been investigated. We thus tested whether an analytical processing mode would be maladaptive relative to an experiential processing mode during anticipatory processing and post-event rumination. Methods: High and low socially anxious participants were induced to engage in either an analytical or experiential processing mode during: (a) anticipatory processing before performing a speech (Experiment 1; N = 94), or (b) post-event rumination after performing a speech (Experiment 2; N = 74). Mood, cognition, and behavioural measures were employed to examine the effects of processing mode. Results: For high socially anxious participants, the modes had a similar effect on self-reported anxiety during both anticipatory processing and post-event rumination. Unexpectedly, relative to the analytical mode, the experiential mode led to stronger high standard and conditional beliefs during anticipatory processing, and stronger unconditional beliefs during post-event rumination. Limitations: These experiments are the first to investigate processing mode during anticipatory processing and post-event rumination. Hence, these results are novel and will need to be replicated. Conclusions: These findings suggest that an experiential processing mode is maladaptive relative to an analytical processing mode during repetitive thinking characteristic of socially anxious individuals.

Journal of behavior therapy and experimental psychiatry · randomised controlled trial · 14 citationsread the source →

Fathers' Representation in Observational Studies on Parenting and Childhood Obesity: A Systematic Review and Content Analysis.

Background: The involvement of fathers in caregiving has increased substantially over the past 30 years. Yet in child and adolescent psychopathology, few studies include fathers as research participants and few present results for fathers separate from those for mothers. We test for the first time whether a similar pattern exists in research on parenting and childhood obesity. Objectives: To conduct a systematic review and quantitative content analysis of observational studies on parenting and childhood obesity to (1) document the inclusion of fathers, relative to mothers, as research participants and (2) examine characteristics of studies that did and did not include fathers. This study presents new data on the number and gender of parent research participants. Search methods: We searched title, abstract, and Medical Subject Headings term fields in 5 research databases (PubMed, EMBASE, Academic Search Premier, PsycINFO, and CINAHL) using terms combining parents or parenting (e.g., mother, father, caregiver, parenting style, food parenting) and obesity (e.g., obesity, body weight, overweight) or obesity-related lifestyle behaviors (e.g., diet, snacking, physical activity, outdoor play, exercise, media use). Selection criteria: We identified and screened studies as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) published between January 2009 and December 2015, examining links between parenting and childhood obesity, including parents or caregivers as research participants, and written in English. We excluded interventions, nonhuman studies, dissertations, conference abstracts, and studies on youths with specific medical conditions. Of 5557 unique studies, 667 studies were eligible. Data collection and analysis: For each of the 667 studies, 4 coders were trained to code characteristics of the study (e.g., publication year, geographic region, journal, study focus) and parent research participants (e.g., parent gender, demographic background, biological relationship with child, and residential status). We established intercoder reliability before coding the full sample of studies (mean Krippendorf's alpha = .79; average percentage agreement = 94%). Main results: Of the studies, 1% included only fathers. By contrast, 36% included only mothers. Although slightly more than 50% of studies (n = 347) included at least 1 father, only 57 studies reported results for fathers separate from those for mothers. When we combined them with studies including only fathers, 10% of studies overall reported results for fathers. Samples sizes of fathers were small compared with mothers. Of studies with fathers, 59% included 50 or fewer fathers, whereas 22% of studies with mothers included 50 or fewer mothers. The mean sample size for fathers across all eligible studies was 139, compared with 672 for mothers. Overall, fathers represented 17% of parent participants across all eligible studies. Conclusions: This study unequivocally demonstrates that fathers are underrepresented in recent observational research on parenting and childhood obesity. Public health implications. The underrepresentation of fathers in obesity research compromises the development of effective family interventions for childhood obesity prevention. Targeted opportunities and incentives are needed to support research with fathers.

American journal of public health · systematic review · 129 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 →

Focus on the future: Episodic future thinking reduces discount rate and snacking.

Obesity seems related to a preference for immediate gratification. By changing this focus on short term benefits to a more future-oriented outlook, delay discounting (impulsive decision making) can be changed by a manipulation of episodic future thinking (EFT). EFT comprises a vivid mental simulation of general future experiences. EFT may also affect consumption of unhealthy foods, which can be seen as a choice for immediate gratification. Recent research shows that future orientation should be tailored to the behavior at outcome. We therefore hypothesize that the effectiveness of EFT on food intake could be enhanced by making the content food-related. We conducted a 2 (future vs past thinking) by 2 (food vs non-food related thoughts) between-subject design experiment in female undergraduates (N = 94), to compare the efficacy of EFT versus the recalling of episodic past events in reducing discount rate and caloric intake. Content of imagery was either unrestricted or food-related. Participants engaged in EFT or control episodic imagery while snacks were offered to freely consume, and next the Monetary Choice Questionnaire was completed as a measure of delay discounting, while again being engaged in EFT or control imagery. Both types of EFT reduced delay discounting, however, only food-related EFT lead to more restricted caloric consumption. Thus, we found evidence that EFT reduced discount rate during decision making. However, in order to restrict caloric intake, EFT should entail food-related imagery. As discount rate and caloric intake were not related in the current sample, the underlying mechanism remains to be discovered. Results however suggest that EFT is a promising technique to resist immediate gratification.

Appetite · randomised controlled trial · 111 citationsread the source →

Resilience, self-esteem and self-compassion in adults with spina bifida.

Study design: Cross-sectional survey. Objectives: To examine factors that may enhance and promote resilience in adults with spina bifida. Setting: Community-based disability organisations within Australia. Methods: Ninety-seven adults with a diagnosis of spina bifida (SB) completed a survey comprising of demographic questions in addition to standardised self-report measures of physical functioning (Craig Handicap Assessment and Reporting Technique), resilience (Connor-Davidson Resilience Scale, 10 item), self-esteem (Rosenberg Self-esteem Scale), self-compassion (Self-compassion Scale) and psychological distress (Depression Anxiety Stress Scales, 21 item). Results: The majority (66%) of respondents reported moderate to high resilience. Physical disability impacted on coping, with greater CD-RISC 10 scores reported by individuals who were functionally independent in addition to those who experienced less medical co-morbidities. Significant correlations between resilience and psychological traits (self-esteem r=0.36, P<0.01; self-compassion r=0.40, P<0.01) were also noted. However, the combined contribution of these variables only accounted for 23% of the total variance in resilience scores (R(2)=0.227, F(5,94)=5.23, P<0.01). Conclusion: These findings extend current understanding of the concept of resilience in adults with a congenital physical disability. The suggestion is that resilience involves a complex interplay between physical determinants of health and psychological characteristics, such as self-esteem and self-compassion. It follows that cognitive behavioural strategies with a focus on self-management may, in part, contribute to the process of resilience in this group. Further large-scale and longitudinal research will help to confirm these findings.

Spinal cord · 41 citationsread the source →

Efficacy of an adjuvant non-face-to-face multimodal lifestyle modification program for patients with treatment-resistant major depression: A randomized controlled trial.

Background: The high prevalence of depression is partly attributable to the poor response of patients to first-line antidepressants. Multimodal programs that promote a healthy lifestyle are successful in treating depression when used as a complementary therapy, but their medium- and long-term benefits have not been demonstrated for patients with treatment-resistant depression (TRD). The main aim of this study was to compare the effectiveness of a lifestyle modification program (LMP) with mindfulness-based cognitive therapy (MBCT) and a placebo-control (written suggestions for lifestyle changes) in Spanish patients with TRD. Methods: This controlled clinical trial randomized 94 patients with TRD into 3 arms. The primary outcome was the Beck Depression Inventory-II (BDI-II) score at baseline, 2, 6 and 12 months. The secondary outcomes were changes in scores that evaluated quality-of-life, adherence to the Mediterranean diet, physical activity, and social support. Results: Relative to the placebo group, the LMP and MBCT groups had significantly better quality of life (p = 0.017; p = 0.027), and the LMP group had significantly better adherence to the Mediterranean diet (p<0.001) and reduced use of antidepressants (p = 0.036). However, the three groups showed no significant differences in BDI-II score. Limitations: Only about half of the planned 180 patients were recruited, in part due to the COVID-19 pandemic. Conclusions: There was no evidence that the LMP treatment significantly reduced symptoms of depression relative to the other groups during the COVID-19 lockdown.

Psychiatry research · randomised controlled trial · 17 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 →

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 →

Effects of evidence-based strategies to reduce the socioeconomic gradient of uptake in the English NHS Bowel Cancer Screening Programme (ASCEND): four cluster-randomised controlled trials.

Background: Uptake in the national colorectal cancer screening programme in England varies by socioeconomic status. We assessed four interventions aimed at reducing this gradient, with the intention of improving the health benefits of screening. Methods: All people eligible for screening (men and women aged 60-74 years) across England were included in four cluster-randomised trials. Randomisation was based on day of invitation. Each trial compared the standard information with the standard information plus the following supplementary interventions: trial 1 (November, 2012), a supplementary leaflet summarising the gist of the key information; trial 2 (March, 2012), a supplementary narrative leaflet describing people's stories; trial 3 (June, 2013), general practice endorsement of the programme on the invitation letter; and trial 4 (July-August, 2013) an enhanced reminder letter with a banner that reiterated the screening offer. Socioeconomic status was defined by the Index of Multiple Deprivation score for each home address. The primary outcome was the socioeconomic status gradient in uptake across deprivation quintiles. This study is registered, number ISRCTN74121020. Findings: As all four trials were embedded in the screening programme, loss to follow-up was minimal (less than 0·5%). Trials 1 (n=163,525) and 2 (n=150,417) showed no effects on the socioeconomic gradient of uptake or overall uptake. Trial 3 (n=265 434) showed no effect on the socioeconomic gradient but was associated with increased overall uptake (adjusted odds ratio [OR] 1·07, 95% CI 1·04-1·10, p<0·0001). In trial 4 (n=168 480) a significant interaction was seen with socioeconomic status gradient (p=0·005), with a stronger effect in the most deprived quintile (adjusted OR 1·11, 95% CI 1·04-1·20, p=0·003) than in the least deprived (1·00, 0·94-1·06, p=0·98). Overall uptake was also increased (1·07, 1·03-1·11, p=0·001). Interpretation: Of four evidence-based interventions, the enhanced reminder letter reduced the socioeconomic gradient in screening uptake, but further reducing inequalities in screening uptake through written materials alone will be challenging. Funding: National Institute for Health Research.

Lancet (London, England) · randomised controlled trial · 112 citationsread the source →

Cognitive behavioural therapy for adherence and depression in patients with HIV: a three-arm randomised controlled trial.

Background: Depression is highly prevalent in people with HIV and has consistently been associated with poor antiretroviral therapy (ART) adherence. Integrating cognitive behavioural therapy (CBT) for depression with adherence counselling using the Life-Steps approach (CBT-AD) has an emerging evidence base. The aim of this study was to test the efficacy of CBT-AD. Methods: In this three-arm randomised controlled trial in HIV-positive adults with depression, we compared CBT-AD with information and supportive psychotherapy plus adherence counselling using the Life-Steps approach (ISP-AD), and with enhanced treatment as usual (ETAU) including Life-Steps adherence counselling only. Participants were recruited from three sites in New England, USA (two hospital settings and one community health centre). Patients were randomly assigned (2:2:1) to receive CBT-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), ISP-AD (one Life-Steps session plus 11 weekly integrated sessions lasting up to 1 h each), or ETAU (one Life-Steps session and five assessment visits roughly every 2 weeks), randomisation was done with allocation software, in pairs, and stratified by three variables: study site, whether or not participants had been prescribed antidepressant medication, and whether or not participants had a history of injection drug use. The primary outcome was ART adherence at the end of treatment (4 month assessment) assessed via electronic pill caps (Medication Event Monitoring System [MEMS]) with correction for pocketed doses, analysed by intention to treat. Findings: Patients were recruited from Feb 26, 2009, to June 21, 2012. Patients who were assigned to CBT-AD (94 randomly assigned, 83 completed assessment) had greater improvements in adherence (estimated difference 1·00 percentage point per visit, 95% CI 0·34 to 1·66, p=0·003) and depression (Center for Epidemiological Studies depression [CESD] score estimated difference -0·41, -0·66 to -0·16, p=0·001; Montgomery-Asberg depression rating scale [MADRS] score -4·69, -8·09 to -1·28, p=0·007; clinical global impression [CGI] score -0·66, -1·11 to -0·21, p=0·005) than did patients who had ETAU (49 assigned, 46 completed assessment) after treatment (4 months). No significant differences in adherence were noted between CBT-AD and ISP-AD (97 assigned, 87 completed assessment). No study-related adverse events were reported. Interpretation: Integrating evidenced-based treatment for depression with evidenced-based adherence counselling is helpful for individuals living with HIV/AIDS and depression. Future efforts should examine how to best disseminate effective psychosocial depression treatments such as CBT-AD to people living with HIV/AIDS and examine the cost-effectiveness of such approaches. Funding: National Institute of Mental Health, National Institute of Allergy and Infectious Diseases.

The lancet. HIV · randomised controlled trial · 114 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 →

Clinical Outcomes of Asynchronous Versus Synchronous Telepsychiatry in Primary Care: Randomized Controlled Trial.

Background: Asynchronous telepsychiatry (ATP; delayed-time) consultations are a novel form of psychiatric consultation in primary care settings. Longitudinal studies comparing clinical outcomes for ATP with synchronous telepsychiatry (STP) are lacking. Objective: This study aims to determine the effectiveness of ATP in improving clinical outcomes in English- and Spanish-speaking primary care patients compared with STP, the telepsychiatry usual care method. Methods: Overall, 36 primary care physicians from 3 primary care clinics referred a heterogeneous sample of 401 treatment-seeking adult patients with nonurgent psychiatric disorders. A total of 184 (94 ATP and 90 STP) English- and Spanish-speaking participants (36/184, 19.6% Hispanic) were enrolled and randomized, and 160 (80 ATP and 80 STP) of them completed baseline evaluations. Patients were treated by their primary care physicians using a collaborative care model in consultation with the University of California Davis Health telepsychiatrists, who consulted with patients every 6 months for up to 2 years using ATP or STP. Primary outcomes (the clinician-rated Clinical Global Impressions [CGI] scale and the Global Assessment of Functioning [GAF]) and secondary outcomes (patients' self-reported physical and mental health and depression) outcomes were assessed every 6 months. Results: For clinician-rated primary outcomes, ATP did not promote greater improvement than STP at 6-month follow-up (ATP vs STP, adjusted difference in follow-up at 6 months vs baseline differences for CGI: 0.2, 95% CI -0.2 to 0.6; P=.28; and GAF: -0.6, 95% CI -3.1 to 1.9; P=.66) or 12-month follow-up (ATP vs STP, adjusted difference in follow-up at 12 months vs baseline differences for CGI: 0.4, 95% CI -0.04 to 0.8; P=.07; and GAF: -0.5, 95% CI -3.3 to 2.2; P=.70), but patients in both arms had statistically and clinically significant improvements in both outcomes. There were no significant differences in improvement from baseline between ATP and STP on any patient self-reported ratings at any follow-up (all P values were between .17 and .96). Dropout rates were higher than predicted but similar between the 2 arms. Of those with baseline visits, 46.8% (75/160) did not have a follow-up at 1 year, and 72.7% (107/147) did not have a follow-up at 2 years. No serious adverse events were associated with the intervention. Conclusions: This is the first longitudinal study to demonstrate that ATP can improve clinical outcomes in English- and Spanish-speaking primary care patients. Although we did not find evidence that ATP is superior to STP in improving clinical outcomes, it is potentially a key part of stepped mental health interventions available in primary care. ATP presents a possible solution to the workforce shortage of psychiatrists and a strategy for improving existing systems of care. Trial registration: ClinicalTrials.gov NCT02084979; https://clinicaltrials.gov/ct2/show/NCT02084979.

Journal of medical Internet research · randomised controlled trial · 22 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 →

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 →

Preventing Peer Violence Against Children: Methods and Baseline Data of a Cluster Randomized Controlled Trial in Pakistan.

Background: Violence against and among children is a global public health problem that annually affects 50% of youth worldwide with major impacts on child development, education, and health including increased probability of major causes of morbidity and mortality in adulthood. It is also associated with the experience of and perpetration of later violence against women. The aim of this article is to describe the intervention, study design, methods, and baseline findings of a cluster randomized controlled trial underway in Pakistan to evaluate a school-based play intervention aiming to reduce peer violence and enhance mental health. Methods: A cluster randomized controlled design is being conducted with boys and girls in grade 6 in 40 schools in Hyderabad, Pakistan, over a period of 2 years. The Multidimensional Peer-Victimization and Peer Perpetration Scales and the Children's Depression Inventory 2 (CDI 2) are being used to measure the primary outcomes while investigator-derived scales are being used to assess domestic violence within the family. Specifics of the intervention, field logistics, ethical, and fidelity management issues employed to test the program's impact on school age youth in a volatile and politically unstable country form this report. Baseline results: A total of 1,752 school-age youth were enrolled and interviewed at baseline. Over the preceding 4 weeks, 94% of the boys and 85% of the girls reported 1 or more occurrences of victimization, and 85% of the boys and 66% of the girls reported 1 or more acts of perpetration. Boys reported more depression compared with girls, as well as higher negative mood and self-esteem scores and more interpersonal and emotional problems. Interpretation: Globally, prevalence of youth violence perpetration and victimization is high and associated with poor physical and emotional health. Applying a randomized controlled design to evaluate a peer violence prevention program built on a firm infrastructure and that is ready for scale-up and sustainability will make an important contribution to identifying evidence-informed interventions that can reduce youth victimization and perpetration.

Global health, science and practice · randomised controlled trial · 28 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 →

Home-based health promotion for older people with mild frailty: the HomeHealth intervention development and feasibility RCT.

Background: Mild frailty or pre-frailty is common and yet is potentially reversible. Preventing progression to worsening frailty may benefit individuals and lower health/social care costs. However, we know little about effective approaches to preventing frailty progression. Objectives: (1) To develop an evidence- and theory-based home-based health promotion intervention for older people with mild frailty. (2) To assess feasibility, costs and acceptability of (i) the intervention and (ii) a full-scale clinical effectiveness and cost-effectiveness randomised controlled trial (RCT). Design: Evidence reviews, qualitative studies, intervention development and a feasibility RCT with process evaluation. Intervention development: Two systematic reviews (including systematic searches of 14 databases and registries, 1990-2016 and 1980-2014), a state-of-the-art review (from inception to 2015) and policy review identified effective components for our intervention. We collected data on health priorities and potential intervention components from semistructured interviews and focus groups with older people (aged 65-94 years) (n = 44), carers (n = 12) and health/social care professionals (n = 27). These data, and our evidence reviews, fed into development of the 'HomeHealth' intervention in collaboration with older people and multidisciplinary stakeholders. 'HomeHealth' comprised 3-6 sessions with a support worker trained in behaviour change techniques, communication skills, exercise, nutrition and mood. Participants addressed self-directed independence and well-being goals, supported through education, skills training, enabling individuals to overcome barriers, providing feedback, maximising motivation and promoting habit formation. Feasibility rct: Single-blind RCT, individually randomised to 'HomeHealth' or treatment as usual (TAU). Setting: Community settings in London and Hertfordshire, UK. Participants: A total of 51 community-dwelling adults aged ≥ 65 years with mild frailty. Main outcome measures: Feasibility - recruitment, retention, acceptability and intervention costs. Clinical and health economic outcome data at 6 months included functioning, frailty status, well-being, psychological distress, quality of life, capability and NHS and societal service utilisation/costs. Results: We successfully recruited to target, with good 6-month retention (94%). Trial procedures were acceptable with minimal missing data. Individual randomisation was feasible. The intervention was acceptable, with good fidelity and modest delivery costs (£307 per patient). A total of 96% of participants identified at least one goal, which were mostly exercise related (73%). We found significantly better functioning (Barthel Index +1.68; p = 0.004), better grip strength (+6.48 kg; p = 0.02), reduced psychological distress (12-item General Health Questionnaire -3.92; p = 0.01) and increased capability-adjusted life-years [+0.017; 95% confidence interval (CI) 0.001 to 0.031] at 6 months in the intervention arm than the TAU arm, with no differences in other outcomes. NHS and carer support costs were variable but, overall, were lower in the intervention arm than the TAU arm. The main limitation was difficulty maintaining outcome assessor blinding. Conclusions: Evidence is lacking to inform frailty prevention service design, with no large-scale trials of multidomain interventions. From stakeholder/public perspectives, new frailty prevention services should be personalised and encompass multiple domains, particularly socialising and mobility, and can be delivered by trained non-specialists. Our multicomponent health promotion intervention was acceptable and delivered at modest cost. Our small study shows promise for improving clinical outcomes, including functioning and independence. A full-scale individually RCT is feasible. Future work: A large, definitive RCT of the HomeHealth service is warranted. Study registration: This study is registered as PROSPERO CRD42014010370 and Current Controlled Trials ISRCTN11986672. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 73. See the NIHR Journals Library website for further project information.

Health technology assessment (Winchester, England) · randomised controlled trial · 64 citationsread the source →

Head-to-head comparison of accuracy of a rapid point-of-care HIV test with oral versus whole-blood specimens: a systematic review and meta-analysis.

Background: The focus on prevention strategies aimed at curbing the HIV epidemic is growing, and therefore screening for HIV has again taken centre stage. Our aim was to establish whether a convenient, non-invasive, HIV test that uses oral fluid was accurate by comparison with the same test with blood-based specimens. Methods: We did a systematic review and meta-analysis to compare the diagnostic accuracy of a rapid HIV-antibody-based point-of-care test (Oraquick advance rapid HIV-1/2, OraSure Technologies Inc, PA, USA) when used with oral versus blood-based specimens in adults. We searched five databases of published work and databases of five key HIV conferences. Studies we deemed eligible were those focused on adults at risk of HIV; we excluded studies in children, in co-infected populations, with self-reported inferior reference standards, and with incomplete reporting of key data items. We assessed the diagnostic accuracy of testing with oral and blood-based specimens with bivariate regression analysis. We computed positive predictive values (PPVs) in high-prevalence and low-prevalence settings with Bayesian methods. Findings: In a direct head-to-head comparison of studies, we identified a pooled sensitivity about 2% lower in oral (98·03%, 95% CI 95·85-99·08) than in blood-based specimens (99·68%, 97·31-99·96), but similar specificity (oral 99·74%, 99·47-99·88; blood 99·91%, 99·84-99·95). Negative likelihood ratios were small and similar (oral 0·019, 0.009-0·040; blood 0·003, 0·001-0·034), but positive likelihood ratios differed (oral 383·37, 183·87-799·31; blood 1105·16, 633·14-2004·37). Although in high-prevalence settings PPVs were similar (oral 98·65%, 95% credible interval 85·71-99·94; blood 98·50, 93·10-99·79), in low-prevalence settings PPVs were lower for oral (88·55%, 77·31-95·87) than blood (97·65%, 95·48-99·09) specimens. Interpretation: Although Oraquick had a high PPV in high-prevalence settings in oral specimens, the slightly lower sensitivity and PPV in low-prevalence settings in oral specimens should be carefully reviewed when planning worldwide expanded initiatives with this popular test.

The Lancet. Infectious diseases · meta-analysis · 128 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 →

What are the unmet supportive care needs of people with cancer? A systematic review.

Goals of work: The identification and management of unmet supportive care needs is an essential component of health care for people with cancer. Information about the prevalence of unmet need can inform service planning/redesign. Materials and methods: A systematic review of electronic databases was conducted to determine the prevalence of unmet supportive care needs at difference time points of the cancer experience. Results: Of 94 articles or reports identified, 57 quantified the prevalence of unmet need. Prevalence of unmet need, their trends and predictors were highly variable in all domains at all time points. The most frequently reported unmet needs were those in the activities of daily living domain (1-73%), followed by psychological (12-85%), information (6-93%), psychosocial (1-89%) and physical (7-89%). Needs within the spiritual (14-51%), communication (2-57%) and sexuality (33-63%) domains were least frequently investigated. Unmet needs appear to be highest and most varied during treatment, however a greater number of individuals were likely to express unmet need post-treatment compared to any other time. Tumour-specific unmet needs were difficult to distinguish. Variations in the classification of unmet need, differences in reporting methods and the diverse samples from which patients were drawn inhibit comparisons of studies. Conclusion: The diversity of methods used in studies hinders analysis of patterns and predictors of unmet need among people with cancer and precludes generalisation. Well-designed, context-specific, prospective studies, using validated instruments and standard methods of analysis and reporting, are needed to benefit future interventional research to identify how best to address the unmet supportive care needs of people with cancer.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · systematic review · 641 citationsread the source →

Psychological predictors of physical activity in the diabetes prevention program.

Objective: To identify the baseline psychological variables before receiving a Diabetes Prevention Program (DPP) lifestyle intervention that predict physical activity levels (PALs) at baseline, 1 year, and end of study (2 to 3 years after randomization). Design and subjects: Of the final 293 DPP lifestyle participants randomized, 274 (94%) completed validated questionnaires at baseline assessing stage of change for PAL, exercise self-efficacy, perceived stress, depression, and anxiety. Statistical analyses performed: Correlations and stepwise multiple regression analyses. Results: At baseline, this subset was similar to the entire DPP lifestyle cohort: mean age was 52.5 years, 65% were women, and mean PAL was 15.7 metabolic equivalent hours per week. Higher levels of baseline leisure PAL correlated with greater readiness to change PAL (r=0.44, P<0.0001), higher exercise self-efficacy (r=0.18, P=0.002), and lower levels of perceived stress (r=-0.16, P=0.009), depression (r=-0.18, P=0.003), and anxiety (r=-0.14, P=0.03), with similar correlations at 1 year and end of study. In multivariate models, being a man, lower levels of depression, and lower body mass index were independent correlates of higher baseline leisure PAL; being a man, greater baseline exercise self-efficacy, and activity level were independent correlates of greater leisure PAL levels at 1 year and end of study. Greater readiness to change PAL at baseline was also an independent correlate of greater PAL at end of study. Conclusions: In this representative sample of DPP lifestyle participants, being a man, lower body mass index, greater readiness for change in PAL, higher exercise self-efficacy, and lower perceived stress, depression, and anxiety scores correlated with higher levels of baseline PAL with similar patterns at 1 year and end of study. These findings may help determine which patients are most likely to increase PAL in lifestyle intervention programs.

Journal of the American Dietetic Association · randomised controlled trial · 107 citationsread the source →

Empowering consumers to PREVENT diet-related diseases through OMICS sciences (PREVENTOMICS): protocol for a parallel double-blinded randomised intervention trial to investigate biomarker-based nutrition plans for weight loss.

Introduction: Personalised nutrition holds immense potential over conventional one-size-fits-all approaches for preventing and treating diet-related diseases, such as obesity. The current study aims to examine whether a personalised nutritional plan produces more favourable health outcomes than a standard approach based on general dietary recommendations in subjects with overweight or obesity and elevated waist circumference. Methods and analysis: This project is a 10-week parallel, double-blinded randomised intervention trial. We plan to include 100 adults aged 18-65 years interested in losing weight, with body mass index ≥27 but<40 kg/m2 and elevated waist circumference (males >94 cm; females >80 cm). Participants will be categorised into one of five predefined 'clusters' based on their individual metabolic biomarker profile and genetic background, and will be randomised in a 1:1 ratio to one of two groups: (1) personalised plan group that will receive cluster-specific meals every day for 6 days a week, in conjunction with a personalised behavioural change programme via electronic push notifications; or (2) control group that will receive meals following the general dietary recommendations in conjunction with generic health behaviour prompts. The primary outcome is the difference between groups (personalised vs control) in the change in fat mass from baseline. Secondary outcomes include changes in weight and body composition, fasting blood glucose and insulin, lipid profile, adipokines, inflammatory biomarkers, and blood pressure. Other outcomes involve measures of physical activity and sleep patterns, health-related quality of life, dietary intake, eating behaviour, and biomarkers of food intake. The effect of the intervention on the primary outcome will be analysed by means of linear mixed models. Ethics and dissemination: The protocol has been approved by the Ethics Committee of the Capital Region, Copenhagen, Denmark. Study findings will be disseminated through peer-reviewed publications, conference presentations and media outlets. Trial registration number: NCT04590989.

BMJ open · clinical trial · 18 citationsread the source →

A mixed-methods feasibility study of an arts-based intervention for patients receiving maintenance haemodialysis.

Background: Haemodialysis can negatively impact quality of life and mental health. Arts-based interventions used successfully in other settings to improve health and well-being, could help address the impact of haemodialysis. This study aimed to evaluate the feasibility and acceptability of conducting a randomised controlled trial (RCT) of an arts-based intervention for patients receiving haemodialysis. Methods: A parallel convergent mixed-methods design was used, including a pilot cluster RCT and qualitative process evaluation. Phase 1 evaluated recruitment and retention rates through a pilot cluster RCT at a single haemodialysis unit in Northern Ireland. Participants included patients who received haemodialysis for ESKD, were over the age of 18 and had the capacity to consent. These participants were randomised to the intervention or control group according to their haemodialysis shift. The intervention involved six one-hour, one-to-one facilitated arts sessions during haemodialysis. Phase 2 explored intervention and trial acceptability through a qualitative process evaluation using semi-structured interviews based on the RE-AIM framework. Participants included 13 patients who participated in phase 1 of the study, including 9 participants from the experimental group and four participants from the control group, and nine healthcare professionals who were present on the unit during implementation. Results: Out of 122 outpatient haemodialysis patients, 94 were assessed as eligible for participation. Twenty-four participants were randomised, meaning 80% of the target sample size was recruited and the attrition rate at 3 months was 12.5% (n = 3). Participants viewed the arts as more accessible and enjoyable than anticipated following implementation. All participants who started the intervention (n = 11) completed the full six sessions. Qualitative benefits of the intervention suggest improvements in mental well-being. Patient choice and facilitation were important factors for successful implementation. Conclusion: An arts-based intervention for patients receiving haemodialysis is acceptable for both patients and healthcare professionals, and a definitive trial is feasible. The intervention may help improve mental-wellbeing in patients receiving haemodialysis, but this requires further investigation in a definitive trial. Trial registration: The trial was prospectively registered on clinicaltrials.gov on 14/8/2018, registration number NCT03629496 .

BMC nephrology · clinical trial · 15 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 →

Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial.

Background: Patients with advanced cancer have reduced quality of life, which tends to worsen towards the end of life. We assessed the effect of early palliative care in patients with advanced cancer on several aspects of quality of life. Methods: The study took place at the Princess Margaret Cancer Centre (Toronto, ON, Canada), between Dec 1, 2006, and Feb 28, 2011. 24 medical oncology clinics were cluster randomised (in a 1:1 ratio, using a computer-generated sequence, stratified by clinic size and tumour site [four lung, eight gastrointestinal, four genitourinary, six breast, two gynaecological]), to consultation and follow-up (at least monthly) by a palliative care team or to standard cancer care. Complete masking of interventions was not possible; however, patients provided written informed consent to participate in their own study group, without being informed of the existence of another group. Eligible patients had advanced cancer, European Cooperative Oncology Group performance status of 0-2, and a clinical prognosis of 6-24 months. Quality of life (Functional Assessment of Chronic Illness Therapy--Spiritual Well-Being [FACIT-Sp] scale and Quality of Life at the End of Life [QUAL-E] scale), symptom severity (Edmonton Symptom Assessment System [ESAS]), satisfaction with care (FAMCARE-P16), and problems with medical interactions (Cancer Rehabilitation Evaluation System Medical Interaction Subscale [CARES-MIS]) were measured at baseline and monthly for 4 months. The primary outcome was change score for FACIT-Sp at 3 months. Secondary endpoints included change score for FACIT-Sp at 4 months and change scores for other scales at 3 and 4 months. This trial is registered with ClinicalTrials.gov, number NCT01248624. Findings: 461 patients completed baseline measures (228 intervention, 233 control); 393 completed at least one follow-up assessment. At 3-months, there was a non-significant difference in change score for FACIT-Sp between intervention and control groups (3·56 points [95% CI -0·27 to 7·40], p=0·07), a significant difference in QUAL-E (2·25 [0·01 to 4·49], p=0·05) and FAMCARE-P16 (3·79 [1·74 to 5·85], p=0·0003), and no difference in ESAS (-1·70 [-5·26 to 1·87], p=0·33) or CARES-MIS (-0·66 [-2·25 to 0·94], p=0·40). At 4 months, there were significant differences in change scores for all outcomes except CARES-MIS. All differences favoured the intervention group. Interpretation: Although the difference in quality of life was non-significant at the primary endpoint, this trial shows promising findings that support early palliative care for patients with advanced cancer. Funding: Canadian Cancer Society, Ontario Ministry of Health and Long Term Care.

Lancet (London, England) · randomised controlled trial · 1215 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 →

Video decision support tool for advance care planning in dementia: randomised controlled trial.

Objective: To evaluate the effect of a video decision support tool on the preferences for future medical care in older people if they develop advanced dementia, and the stability of those preferences after six weeks. Design: Randomised controlled trial conducted between 1 September 2007 and 30 May 2008. Setting Four primary care clinics (two geriatric and two adult medicine) affiliated with three academic medical centres in Boston. Participants: Convenience sample of 200 older people (>or=65 years) living in the community with previously scheduled appointments at one of the clinics. Mean age was 75 and 58% were women. Intervention: Verbal narrative alone (n=106) or with a video decision support tool (n=94). Main outcome measures: Preferred goal of care: life prolonging care (cardiopulmonary resuscitation, mechanical ventilation), limited care (admission to hospital, antibiotics, but not cardiopulmonary resuscitation), or comfort care (treatment only to relieve symptoms). Preferences after six weeks. The principal category for analysis was the difference in proportions of participants in each group who preferred comfort care. Results: Among participants receiving the verbal narrative alone, 68 (64%) chose comfort care, 20 (19%) chose limited care, 15 (14%) chose life prolonging care, and three (3%) were uncertain. In the video group, 81 (86%) chose comfort care, eight (9%) chose limited care, four (4%) chose life prolonging care, and one (1%) was uncertain (chi(2)=13.0, df=3, P=0.003). Among all participants the factors associated with a greater likelihood of opting for comfort care were being a college graduate or higher, good or better health status, greater health literacy, white race, and randomisation to the video arm. In multivariable analysis, participants in the video group were more likely to prefer comfort care than those in the verbal group (adjusted odds ratio 3.9, 95% confidence interval 1.8 to 8.6). Participants were re-interviewed after six weeks. Among the 94/106 (89%) participants re-interviewed in the verbal group, 27 (29%) changed their preferences (kappa=0.35). Among the 84/94 (89%) participants re-interviewed in the video group, five (6%) changed their preferences (kappa=0.79) (P<0.001 for difference). Conclusion: Older people who view a video depiction of a patient with advanced dementia after hearing a verbal description of the condition are more likely to opt for comfort as their goal of care compared with those who solely listen to a verbal description. They also have more stable preferences over time. Trial registration: Clinicaltrials.gov NCT00704886.

BMJ (Clinical research ed.) · randomised controlled trial · 207 citationsread the source →

Stepped care treatment of postpartum depression: impact on treatment, health, and work outcomes.

Purpose: The purpose of this study was to pilot a stepped collaborative care intervention for women with postpartum depression and evaluate health differences between self-diagnosed depressed and nondepressed women. Methods: Five hundred six mothers of infants from 7 clinics completed surveys at 0 to 1, 2, 4, 6, and 9 months postpartum and a Structured Clinical Interview for DSM-IV (SCID). SCID-positive depressed women were randomized to stepped collaborative care or usual care. Nine-month treatment, health, and work outcomes were evaluated for stepped care women (n = 19) versus control depressed women (n = 20), and self-diagnosed depressed women (n = 122) versus nondepressed women (n = 344). Results: Forty-five women had SCID-positive depression whereas 122 had self-diagnosed depression. For SCID-positive depressed women, the stepped care intervention increased mothers' awareness of their depression diagnosis (100% vs 61%; P = .008) and their receipt of treatment (94% vs 56%; P = .019). Self-diagnosed depressed women (vs nondepressed women) had more depressive symptoms and acute care visits, worse general and mental health, and greater impact of health problems on regular activities. Conclusions: The stepped care intervention improved women's knowledge of their postpartum depression diagnosis and their receipt of treatment. However, our formal diagnostic procedures missed many women whose depressed mood interfered with their health and function.

Journal of the American Board of Family Medicine : JABFM · randomised controlled trial · 34 citationsread the source →

Psychosocial factors related to non-persistence with adjuvant endocrine therapy among women with breast cancer: the Breast Cancer Quality of Care Study (BQUAL).

Non-adherence to adjuvant endocrine therapy (ET) for breast cancer (BC) is common. Our goal was to determine the associations between psychosocial factors and ET non-persistence. We recruited women with BC receiving care in an integrated healthcare system between 2006 and 2010. Using a subset of patients treated with ET, we investigated factors related to ET non-persistence (discontinuation) based on pharmacy records (≥90 days gap). Serial interviews were conducted at baseline and every 6 months. The Functional Assessment of Cancer Therapy (FACT), Medical Outcomes Survey, Treatment Satisfaction Questionnaire (TSQM), Impact of Events Scale (IES), Interpersonal Processes of Care measure, and Decision-making beliefs and concerns were measured. Multivariate models assessed factors associated with non-persistence. Of the 523 women in our final cohort who initiated ET and had a subsequent evaluation, 94 (18 %) were non-persistent over a 2-year follow-up. The cohort was primarily white (74.4 %), stage 1 (60.6 %), and on an aromatase inhibitor (68.1 %). Women in the highest income category had a lower odds of being non-persistent (OR 0.43, 95 % CI 0.23-0.81). Quality of life and attitudes toward ET at baseline were associated with non-persistence. At follow-up, the FACT, TSQM, and IES were associated with non-persistence (p < 0.001). Most women continued ET. Women who reported a better attitude toward ET, better quality of life, and more treatment satisfaction, were less likely to be non-persistent and those who reported intrusive/avoidant thoughts were more likely to be non-persistent. Interventions to enhance the psychosocial well-being of patients should be evaluated to increase adherence.

Breast cancer research and treatment · 53 citationsread the source →

Medicinal plants used in Jeddah, Saudi Arabia: A gender perspective.

Ethnopharmacological relevance: Very few studies examining quantitatively gender differences in the knowledge and use of medicinal plants exist for the Arab world. Differences in ethnobotanical knowledge of medicinal plants between men and women in Jeddah are explored here for the first time. Aim of the study: Our study aims to document urban medicinal plant knowledge in Jeddah, and to answer the following questions: (1) What medicinal plants are used by Saudis in Jeddah? (2) To what extent do men and women use medicinal plants? (3) Are plants used by men significantly different to those used by women? And, (4) do men and women learn about medicinal plants in different ways? Given the gendered nature of space and relations in the Arab world, we hypothesise that men and women learn about plants in different ways and that this will contribute to explain any possible differences. Materials and methods: Ethnobotanical fieldwork took place in Jeddah from August 2018 to September 2019. Individual free-listing, semi-structured interviews and an online survey questionnaire were carried out to document local medicinal plant. In total, 50 men and 50 women were interviewed face-to-face and 344 people responded to the questionnaire, of which 154 were men and 190 were women. Results: A total of 94 medicinal plant vernacular names were documented representing 85 different plant species belonging to 37 families. Men cited 63 plants (33 plant families) and women 83 (36 plant families). Sixty-one plants were cited by both men and women, two only by men and 22 only by women. Men and women learn in similar ways, but generally use medicinal plants to treat different ailments. Women rely on medicinal plant use to a larger extent. Conclusion: Medicinal plant use is dependent on gendered social roles and experience, as well as preference for biomedicine or medicinal plant use. Men and women use similar plants, but women have greater knowledge that increases with age. Given the food-medicine continuum, women's double role of family food and care providers may explain their expertise in medicinal plant use.

Journal of ethnopharmacology · cohort or longitudinal · 21 citationsread the source →

Accuracy of the Enhanced Liver Fibrosis Test vs FibroTest, Elastography, and Indirect Markers in Detection of Advanced Fibrosis in Patients With Alcoholic Liver Disease.

Background & aims: Alcohol is the leading cause of cirrhosis and liver-related mortality, but we lack serum markers to detect compensated disease. We compared the accuracy of the Enhanced Liver Fibrosis test (ELF), the FibroTest, liver stiffness measurements (made by transient elastography and 2-dimensional shear-wave elastography), and 6 indirect marker tests in detection of advanced liver fibrosis (Kleiner stage ≥F3). Methods: We performed a prospective study of 10 liver fibrosis markers (patented and not), all performed on the same day. Patients were recruited from primary centers (municipal alcohol rehabilitation, n = 128; 6% with advanced fibrosis) and secondary health care centers (hospital outpatient clinics, n = 161; 36% with advanced fibrosis) in the Region of Southern Denmark from 2013 through 2016. Biopsy-verified fibrosis stage was used as the reference standard. The primary aim was to validate ELF in detection of advanced fibrosis in patients with alcoholic liver disease recruited from primary and secondary health care centers, using the literature-based cutoff value of 10.5. Secondary aims were to assess the diagnostic accuracy of ELF for significant fibrosis and cirrhosis and to determine whether combinations of fibrosis markers increase diagnostic yield. Results: The ELF identified patients with advanced liver fibrosis with an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% confidence interval 0.89-0.96); findings did not differ significantly between patients from primary vs secondary care (P = .917). ELF more accurately identified patients with advanced liver fibrosis than indirect marker tests, but ELF and FibroTest had comparable diagnostic accuracies (AUROC of FibroTest, 0.90) (P = .209 for comparison with ELF). Results from the ELF and FibroTest did not differ significantly from those of liver stiffness measurement in intention-to-diagnose analyses (AUROC for transient elastography, 0.90), but did differ in the per-protocol analysis (AUROC for transient elastography, 0.97) (P = .521 and .004 for comparison with ELF). Adding a serum marker to transient elastography analysis did not increase accuracy. For patients in primary care, ELF values below 10.5 and FibroTest values below 0.58 had negative predictive values for advanced liver fibrosis of 98% and 94%, respectively. Conclusion: In a prospective, direct comparison of tests, ELF and FibroTest identified advanced liver fibrosis in alcoholic patients from primary and secondary care with high diagnostic accuracy (AUROC values of 0.90 or higher using biopsy as reference). Advanced fibrosis can be ruled out in primary health care patients based on an ELF value below 10.5 or a FibroTest value below 0.58.

Gastroenterology · cohort or longitudinal · 208 citationsread the source →

Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression.

Background: Ketamine is reported to have rapid antidepressant effects; however, there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in a larger sample, inclusive of the original. Methods: Participants with TRD (n = 24) underwent a washout of antidepressant medication followed by a series of up to six IV infusions of ketamine (.5 mg/kg) administered open-label three times weekly over a 12-day period. Participants meeting response criteria were monitored for relapse for up to 83 days from the last infusion. Results: The overall response rate at study end was 70.8%. There was a large mean decrease in Montgomery-Åsberg Depression Rating Scale score at 2 hours after the first ketamine infusion (18.9 ± 6.6, p < .001), and this decrease was largely sustained for the duration of the infusion period. Response at study end was strongly predicted by response at 4 hours (94% sensitive, 71% specific). Among responders, median time to relapse after the last ketamine infusion was 18 days. Conclusions: Ketamine was associated with a rapid antidepressant effect in TRD that was predictive of a sustained effect. Future controlled studies will be required to identify strategies to maintain an antidepressant response among patients who benefit from a course of ketamine.

Biological psychiatry · clinical trial · 595 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 →

Depression, comorbid anxiety disorders, and heart rate variability in physically healthy, unmedicated patients: implications for cardiovascular risk.

Context: There is evidence that heart rate variability (HRV) is reduced in major depressive disorder (MDD), although there is debate about whether this effect is caused by medication or the disorder per se. MDD is associated with a two to fourfold increase in the risk of cardiac mortality, and HRV is a robust predictor of cardiac mortality; determining a direct link between HRV and not only MDD, but common comorbid anxiety disorders, will point to psychiatric indicators for cardiovascular risk reduction. Objective: To determine in physically healthy, unmedicated patients whether (1) HRV is reduced in MDD relative to controls, and (2) HRV reductions are driven by MDD alone, comorbid generalized anxiety disorder (GAD, characterized by anxious anticipation), or comorbid panic and posttraumatic stress disorders (PD/PTSD, characterized by anxious arousal). Design, setting, and patients: A case-control study in 2006 and 2007 on 73 MDD patients, including 24 without anxiety comorbidity, 24 with GAD, and 14 with PD/PTSD. Seventy-three MDD and 94 healthy age- and sex-matched control participants were recruited from the general community. Participants had no history of drug addiction, alcoholism, brain injury, loss of consciousness, stroke, neurological disorder, or serious medical conditions. There were no significant differences between the four groups in age, gender, BMI, or alcohol use. Main outcome measures: HRV was calculated from electrocardiography under a standardized short-term resting state condition. Results: HRV was reduced in MDD relative to controls, an effect associated with a medium effect size. MDD participants with comorbid generalized anxiety disorder displayed the greatest reductions in HRV relative to controls, an effect associated with a large effect size. Conclusions: Unmedicated, physically healthy MDD patients with and without comorbid anxiety had reduced HRV. Those with comorbid GAD showed the greatest reductions. Implications for cardiovascular risk reduction strategies in otherwise healthy patients with psychiatric illness are discussed.

PloS one · cohort or longitudinal · 298 citationsread the source →

The familial risk of autism.

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

JAMA · cohort or longitudinal · 702 citationsread the source →

Personalization strategies in digital mental health interventions: a systematic review and conceptual framework for depressive symptoms.

Introduction: Personalization is a much-discussed approach to improve adherence and outcomes for Digital Mental Health interventions (DMHIs). Yet, major questions remain open, such as (1) what personalization is, (2) how prevalent it is in practice, and (3) what benefits it truly has. Methods: We address this gap by performing a systematic literature review identifying all empirical studies on DMHIs targeting depressive symptoms in adults from 2015 to September 2022. The search in Pubmed, SCOPUS and Psycinfo led to the inclusion of 138 articles, describing 94 distinct DMHIs provided to an overall sample of approximately 24,300 individuals. Results: Our investigation results in the conceptualization of personalization as purposefully designed variation between individuals in an intervention's therapeutic elements or its structure. We propose to further differentiate personalization by what is personalized (i.e., intervention content, content order, level of guidance or communication) and the underlying mechanism [i.e., user choice, provider choice, decision rules, and machine-learning (ML) based approaches]. Applying this concept, we identified personalization in 66% of the interventions for depressive symptoms, with personalized intervention content (32% of interventions) and communication with the user (30%) being particularly popular. Personalization via decision rules (48%) and user choice (36%) were the most used mechanisms, while the utilization of ML was rare (3%). Two-thirds of personalized interventions only tailored one dimension of the intervention. Discussion: We conclude that future interventions could provide even more personalized experiences and especially benefit from using ML models. Finally, empirical evidence for personalization was scarce and inconclusive, making further evidence for the benefits of personalization highly needed. Systematic review registration: Identifier: CRD42022357408.

Frontiers in digital health · review · 61 citationsread the source →

Health outcomes in people 2 years after surviving hospitalisation with COVID-19: a longitudinal cohort study.

Background: With the ongoing COVID-19 pandemic, growing evidence shows that a considerable proportion of people who have recovered from COVID-19 have long-term effects on multiple organs and systems. A few longitudinal studies have reported on the persistent health effects of COVID-19, but the follow-up was limited to 1 year after acute infection. The aim of our study was to characterise the longitudinal evolution of health outcomes in hospital survivors with different initial disease severity throughout 2 years after acute COVID-19 infection and to determine their recovery status. Methods: We did an ambidirectional, longitudinal cohort study of individuals who had survived hospitalisation with COVID-19 and who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7 and May 29, 2020. We measured health outcomes 6 months (June 16-Sept 3, 2020), 12 months (Dec 16, 2020-Feb 7, 2021), and 2 years (Nov 16, 2021-Jan 10, 2022) after symptom onset with a 6-min walking distance (6MWD) test, laboratory tests, and a series of questionnaires on symptoms, mental health, health-related quality of life (HRQoL), return to work, and health-care use after discharge. A subset of COVID-19 survivors received pulmonary function tests and chest imaging at each visit. Age-matched, sex-matched, and comorbidities-matched participants without COVID-19 infection (controls) were introduced to determine the recovery status of COVID-19 survivors at 2 years. The primary outcomes included symptoms, modified British Medical Research Council (mMRC) dyspnoea scale, HRQoL, 6MWD, and return to work, and were assessed in all COVID-19 survivors who attended all three follow-up visits. Symptoms, mMRC dyspnoea scale, and HRQoL were also assessed in controls. Findings: 2469 patients with COVID-19 were discharged from Jin Yin-tan Hospital between Jan 7 and May 29, 2020. 1192 COVID-19 survivors completed assessments at the three follow-up visits and were included in the final analysis, 1119 (94%) of whom attended the face-to-face interview 2 years after infection. The median age at discharge was 57·0 years (48·0-65·0) and 551 (46%) were women. The median follow-up time after symptom onset was 185·0 days (IQR 175·0-197·0) for the visit at 6 months, 349·0 days (337·0-360·0) for the visit at 12 months, and 685·0 days (675·0-698·0) for the visit at 2 years. The proportion of COVID-19 survivors with at least one sequelae symptom decreased significantly from 777 (68%) of 1149 at 6 months to 650 (55%) of 1190 at 2 years (p<0·0001), with fatigue or muscle weakness always being the most frequent. The proportion of COVID-19 survivors with an mMRC score of at least 1 was 168 (14%) of 1191 at 2 years, significantly lower than the 288 (26%) of 1104 at 6 months (p<0·0001). HRQoL continued to improve in almost all domains, especially in terms of anxiety or depression: the proportion of individuals with symptoms of anxiety or depression decreased from 256 (23%) of 1105 at 6 months to 143 (12%) 1191 at 2 years (p<0·0001). The proportion of individuals with a 6MWD less than the lower limit of the normal range declined continuously in COVID-19 survivors overall and in the three subgroups of varying initial disease severity. 438 (89%) of 494 COVID-19 survivors had returned to their original work at 2 years. Survivors with long COVID symptoms at 2 years had lower HRQoL, worse exercise capacity, more mental health abnormality, and increased health-care use after discharge than survivors without long COVID symptoms. COVID-19 survivors still had more prevalent symptoms and more problems in pain or discomfort, as well as anxiety or depression, at 2 years than did controls. Additionally, a significantly higher proportion of survivors who had received higher-level respiratory support during hospitalisation had lung diffusion impairment (43 [65%] of 66 vs 24 [36%] of 66, p=0·0009), reduced residual volume (41 [62%] vs 13 [20%], p<0·0001), and total lung capacity (26 [39%] vs four [6%], p<0·0001) than did controls. Interpretation: Regardless of initial disease severity, COVID-19 survivors had longitudinal improvements in physical and mental health, with most returning to their original work within 2 years; however, the burden of symptomatic sequelae remained fairly high. COVID-19 survivors had a remarkably lower health status than the general population at 2 years. The study findings indicate that there is an urgent need to explore the pathogenesis of long COVID and develop effective interventions to reduce the risk of long COVID.

The Lancet. Respiratory medicine · 462 citationsread the source →

How Do Corticosteroids Work in Asthma?

Reviews2 September 2003How Do Corticosteroids Work in Asthma?Peter J. Barnes, DM, DSc and Ian M. Adcock, PhDPeter J. Barnes, DM, DScFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this author and Ian M. Adcock, PhDFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-5_Part_1-200309020-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesAsthma is the most common chronic disease in westernized countries. Patients with asthma have an underlying chronic inflammation of the airways characterized by activated mast cells, eosinophils, and T-helper 2 lymphocytes. This results in increased responsiveness of the airways to such triggers as exercise, allergens, and air pollutants. This chronic inflammation underlies the typical symptoms of asthma, which include intermittent wheezing, coughing, shortness of breath, and chest tightness. Corticosteroids are the most effective treatment for asthma, and inhaled corticosteroids have become first-line treatment for children and adults with persistent symptoms. Corticosteroids suppress the chronic airway inflammation in patients with asthma, and the molecular ...References1. Busse WW, Lemanske RF. Asthma. N Engl J Med. 2001;344:350-62. [PMID: 11172168] CrossrefMedlineGoogle Scholar2. Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998;50:515-96. [PMID: 9860804] MedlineGoogle Scholar3. Barnes PJ, Adcock IM. Transcription factors and asthma. Eur Respir J. 1998;12:221-34. [PMID: 9701442] CrossrefMedlineGoogle Scholar4. Hart LA, Krishnan VL, Adcock IM, Barnes PJ, Chung KF. Activation and localization of transcription factor, nuclear factor-B, in asthma. 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Molecular regulation of granulocyte macrophage colony-stimulating factor in human lung epithelial cells by interleukin (IL)-1, IL-4, and IL-13 involves both transcriptional and post-transcriptional mechanisms. Am J Respir Cell Mol Biol. 2000;22:582-9. [PMID: 10783130] CrossrefMedlineGoogle Scholar37. Caelles C, Gonzalez-Sancho JM, Munoz A. Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 1997;11:3351-64. [PMID: 9407028] CrossrefMedlineGoogle Scholar38. Vanden Berghe W, Vermeulen L, De Wilde G, De Bosscher K, Boone E, Haegeman G. Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol. 2000;60:1185-95. [PMID: 11007957] CrossrefMedlineGoogle Scholar39. Lasa M, Brook M, Saklatvala J, Clark AR. Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. Mol Cell Biol. 2001;21:771-80. [PMID: 11154265] CrossrefMedlineGoogle Scholar40. 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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. 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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. 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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 →

Domestic violence in pregnancy: prevalence and characteristics of the pregnant woman.

Aims and objectives: To determine the prevalence of domestic violence (physical, psychological or sexual) during pregnancy and to characterise these women. Background: Pregnant women are not immune to domestic violence and therefore may be subject to any form of physical, psychological or sexual violence by partners. Health professionals' knowledge and awareness are important in the identification and intervention of pregnant women who experience domestic violence. Methods: Quantitative, descriptive, correlational study, using a nonprobabilistic convenience sample consisting of a total of 852 postpartum women, of whom 370 were experiencing domestic violence according to the criteria adopted through the modified scale of prevalence, applied between February-June 2012 in two Portuguese public health institutions. Authorisation was given by the Ethics Committees/Administration Councils of both institutions involved and the National Committee of Data Protection. Results: The prevalence of DV during pregnancy was 43·4% (physical violence - 21·9%; psychological violence - 43·2%; and sexual violence - 19·6%). These women had the following profile: immigrant (OR = 5·70; IC95% 3·32-9·78), non-Caucasian (OR = 6·27; IC95% 3·76-10·46), single/divorced/widowed (OR = 2·28; IC95% 1·70-3·05), academic qualifications up to year 9 (OR = 4·94; IC95% 3·31-7·37); between 10-12 years of schooling (OR = 2·36; IC95% 1·70-3·29); unemployed (OR = 2·01; IC95% 1·50-2·69); and with a monthly income <1000 euros (OR = 1·90; IC95% 1·44-2·50). Through logistic regression, the following protective factors have been identified: nationality (Portuguese), race (Caucasian) and place of residence (city). Conclusions: Almost half of the sample had experienced some form of domestic violence. This is associated with certain sociodemographic factors identified in the study. Psychological violence was the most prevalent during pregnancy. Relevance to clinical practice: Knowledge of the prevalence and characteristics of pregnant women who experience domestic violence is of paramount importance in planning appropriate strategies for their needs during pregnancy. Results indicate the need for nurses to intervene when warning signs of domestic violence against pregnant women are detected.

Journal of clinical nursing · 30 citationsread the source →