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Depression and anxiety in long-term cancer survivors compared with spouses and healthy controls: a systematic review and meta-analysis.

Background: Cancer survival has improved in the past 20 years, affecting the long-term risk of mood disorders. We assessed whether depression and anxiety are more common in long-term survivors of cancer compared with their spouses and with healthy controls. Methods: We systematically searched Medline, PsycINFO, Embase, Science Direct, Ingenta Select, Ovid, and Wiley Interscience for reports about the prevalence of mood disorders in patients diagnosed with cancer at least 2 years previously. We also searched the records of the International Psycho-oncology Society and for reports that cited relevant references. Three investigators independently extracted primary data. We did a random-effects meta-analysis of the prevalences of depression and anxiety in cancer patients compared with spouses and healthy controls. Findings: Our search returned 144 results, 43 were included in the main analysis: for comparisons with healthy controls, 16 assessed depression and ten assessed anxiety; of the comparisons with spouses, 12 assessed depression and five assessed anxiety. The prevalence of depression was 11·6% (95% CI 7·7-16·2) in the pooled sample of 51 381 cancer survivors and 10·2% (8·0-12·6) in 217 630 healthy controls (pooled relative risk [RR] 1·11, 95% CI 0·96-1·27; p=0·17). The prevalence of anxiety was 17·9% (95% CI 12·8-23·6) in 48 964 cancer survivors and 13·9% (9·8-18·5) in 226 467 healthy controls (RR 1·27, 95% CI 1·08-1·50; p=0·0039). Neither the prevalence of depression (26·7% vs 26·3%; RR 1·01, 95% CI 0·86-1·20; p=0·88) nor the prevalence of anxiety (28·0% vs 40·1%; RR 0·71, 95% CI 0·44-1·14; p=0·16) differed significantly between cancer patients and their spouses. Interpretation: Our findings suggest that anxiety, rather than depression, is most likely to be a problem in long-term cancer survivors and spouses compared with healthy controls. Efforts should be made to improve recognition and treatment of anxiety in long-term cancer survivors and their spouses. Funding: None.

The Lancet. Oncology · meta-analysis · 536 citationsread the source →

Psychotherapy for depression in older veterans via telemedicine: a randomised, open-label, non-inferiority trial.

Background: Many older adults with major depression, particularly veterans, do not have access to evidence-based psychotherapy. Telemedicine could increase access to best-practice care for older adults facing barriers of mobility, stigma, and geographical isolation. We aimed to establish non-inferiority of behavioural activation therapy for major depression delivered via telemedicine to same-room care in largely male, older adult veterans. Methods: In this randomised, controlled, open-label, non-inferiority trial, we recruited veterans (aged ≥58 years) meeting DSM-IV criteria for major depressive disorder from the Ralph H Johnson Veterans Affairs Medical Center and four associated community outpatient-based clinics in the USA. We excluded actively psychotic or demented people, those with both suicidal ideation and clear intent, and those with substance dependence. The study coordinator randomly assigned participants (1:1; block size 2-6; stratified by race; computer-generated randomisation sequence by RGK) to eight sessions of behavioural activation for depression either via telemedicine or in the same room. The primary outcome was treatment response according to the Geriatric Depression Scale (GDS) and Beck Depression Inventory (BDI; defined as a 50% reduction in symptoms from baseline at 12 months), and Structured Clinical Interview for DSM-IV, clinician version (defined as no longer being diagnosed with major depressive disorder at 12 months follow-up), in the per-protocol population (those who completed at least four treatment sessions and for whom all outcome measurements were done). Those assessing outcomes were masked. The non-inferiority margin was 15%. This trial is registered with ClinicalTrials.gov, number NCT00324701. Findings: Between April 1, 2007, and July 31, 2011, we screened 780 patients, and the study coordinator randomly assigned participants to either telemedicine (120 [50%]) or same-room treatment (121 [50%]). We included 100 (83%) patients in the per-protocol analysis in the telemedicine group and 104 (86%) in the same-room group. Treatment response according to GDS did not differ significantly between the telemedicine (22 [22·45%, 90% CI 15·52-29·38] patients) and same-room (21 [20·39%, 90% CI 13·86-26·92]) groups, with an absolute difference of 2·06% (90% CI -7·46 to 11·58). Response according to BDI also did not differ significantly (telemedicine 19 [24·05%, 90% CI 16·14-31·96] patients; same room 19 [23·17%, 90% CI 15·51-30·83]), with an absolute difference of 0·88% (90% CI -10·13 to 11·89). Response on the Structured Clinical Interview for DSM-IV, clinician version, also did not differ significantly (39 [43·33%, 90% CI 34·74-51·93] patients in the telemedicine group and 46 [48·42%, 90% CI 39·99-56·85] in the same-room group), with a difference of -5·09% (-17·13 to 6·95; p=0·487). Results from the intention-to-treat population were similar. MEM analyses showed that no significant differences existed between treatment trajectories over time for BDI and GDS. The criteria for non-inferiority were met. We did not note any adverse events. Interpretation: Telemedicine-delivered psychotherapy for older adults with major depression is not inferior to same-room treatment. This finding shows that evidence-based psychotherapy can be delivered, without modification, via home-based telemedicine, and that this method can be used to overcome barriers to care associated with distance from and difficulty with attendance at in-person sessions in older adults. Funding: US Department of Veterans Affairs.

The lancet. Psychiatry · randomised controlled trial · 123 citationsread the source →

Cognitive-behavioral therapy vs risperidone for augmenting serotonin reuptake inhibitors in obsessive-compulsive disorder: a randomized clinical trial.

Importance: Obsessive-compulsive disorder (OCD) is one of the world's most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP). Objective: To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD. Design, setting, and participants: A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial. Interventions: While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks. Main outcome and measure: The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity. Results: Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean [SE], -9.72 [1.38]; P < .001 vs placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life. Conclusions and relevance: Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile. Trial registration: clinicaltrials.gov Identifier: NCT00389493.

JAMA psychiatry · randomised controlled trial · 143 citationsread the source →

HIV combination prevention and declining orphanhood among adolescents, Rakai, Uganda, 2001-18: an observational community cohort study.

Background: Orphanhood increased markedly in the 1980s and 1990s in sub-Saharan Africa because of HIV-related mortality. Little is known about the contribution of HIV interventions, such as antiretroviral therapy (ART) and male medical circumcision, to more recent trends in orphanhood. In this study, we examined trends over time in maternal-only, paternal-only, and double orphanhood among adolescents before and after ART and male medical circumcision became widely available in the Rakai region of south-central Uganda. We sought to understand the association between adolescent orphanhood and HIV combination prevention (community-level ART use and prevalence of male medical circumcision). We hypothesised that increasing combination prevention, including greater use of ART and higher prevalence of male medical circumcision, would be associated with a lower probability of orphanhood. Methods: We examined the prevalence of orphanhood among adolescents aged 15-19 years, before and after roll-out of ART in mid-2004 and male medical circumcision in 2007, using data from 28 continuously followed communities within the Rakai Community Cohort Study. We used multinomial logistic regression with clustered SEs to estimate adjusted relative risk ratios (RRs) for maternal-only, paternal-only, and double orphanhood compared with non-orphanhood over 11 survey rounds between 2001 and 2018. Controlling for community HIV prevalence, household socioeconomic status, and adolescent age, we examined the association between community prevalence of ART use among people living with HIV and prevalence of male circumcision, including traditional circumcision. The primary outcome was orphanhood among adolescents aged 15-19 years. Findings: Orphanhood declined from 52% (920 of 1768 participants) in 2001-02 to 23% (592 of 2609 participants) by 2016-18 (p<0·0001), while double orphanhood declined from 20% (346 of 1768 participants) to 3% (86 of 2609 participants) (p<0·0001). Community prevalence of ART use among people living with HIV increased from 11% (105 of 945 participants) in 2005-06 to 78% (1163 of 1485 participants) in 2016-18. Male circumcision rates rose from 19% (147 of 790 participants) in 2005-06 to 65% (3535 of 5433 participants) in 2016-18. In the multinomial logistic regression model, a 10% increase in community prevalence of ART use was associated with a decrease in maternal orphanhood (adjusted relative RR 0·90, 95% CI 0·85-0·95) and double orphanhood (0·80, 0·75-0·85). In the post-ART era, a 10% increase in the community prevalence of male circumcision was associated with a decrease in paternal orphanhood (2005-18, adjusted relative RR 0·92, 0·87-0·97) and double orphanhood (0·91, 0·85-0·98). Interpretation: Widespread availability and uptake of HIV combination prevention was associated with marked reductions in orphanhood among adolescents. Reductions in orphanhood promise improved health and social outcomes for young people. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, and the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases.

The lancet. HIV · cohort or longitudinal · 5 citationsread the source →

Comparative efficacy and acceptability of antidepressants, psychotherapies, and their combination for acute treatment of children and adolescents with depressive disorder: a systematic review and network meta-analysis.

Background: Depressive disorders are common in children and adolescents. Antidepressants, psychotherapies, and their combination are often used in routine clinical practice; however, available evidence on the comparative efficacy and safety of these interventions is inconclusive. Therefore, we sought to compare and rank all available treatment interventions for the acute treatment of depressive disorders in children and adolescents. Methods: We did a systematic review and network meta-analysis. We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, PsycINFO, ProQuest, CINAHL, LiLACS, international trial registries, and the websites of regulatory agencies for published and unpublished randomised controlled trials from database inception until Jan 1, 2019. We included placebo-controlled and head-to-head trials of 16 antidepressants, seven psychotherapies, and five combinations of antidepressant and psychotherapy that are used for the acute treatment of children and adolescents (≤18 years old and of both sexes) with depressive disorder diagnosed according to standard operationalised criteria. Trials recruiting participants with treatment-resistant depression, bipolar disorder, psychotic depression, treatment duration of less than 4 weeks, or an overall sample size of fewer than ten patients were excluded. We extracted data following a predefined hierarchy of outcome measures, and assessed risk of bias and certainty of evidence using validated methods. Primary outcomes were efficacy (change in depressive symptoms) and acceptability (treatment discontinuation due to any cause). We estimated summary standardised mean differences (SMDs) or odds ratios (ORs) with credible intervals (CrIs) using network meta-analysis with random effects. This study was registered with PROSPERO, number CRD42015020841. Findings: From 20 366 publications, we included 71 trials (9510 participants). Depressive disorders in most studies were moderate to severe. In terms of efficacy, fluoxetine plus cognitive behavioural therapy (CBT) was more effective than CBT alone (-0·78, 95% CrI -1·55 to -0·01) and psychodynamic therapy (-1·14, -2·20 to -0·08), but not more effective than fluoxetine alone (-0·22, -0·86 to 0·42). No pharmacotherapy alone was more effective than psychotherapy alone. Only fluoxetine plus CBT and fluoxetine were significantly more effective than pill placebo or psychological controls (SMDs ranged from -1·73 to -0·51); and only interpersonal therapy was more effective than all psychological controls (-1·37 to -0·66). Nortriptyline (SMDs ranged from 1·04 to 2·22) and waiting list (SMDs ranged from 0·67 to 2·08) were less effective than most active interventions. In terms of acceptability, nefazodone and fluoxetine were associated with fewer dropouts than sertraline, imipramine, and desipramine (ORs ranged from 0·17 to 0·50); imipramine was associated with more dropouts than pill placebo, desvenlafaxine, fluoxetine plus CBT, and vilazodone (2·51 to 5·06). Most of the results were rated as "low" to "very low" in terms of confidence of evidence according to Confidence In Network Meta-Analysis. Interpretation: Despite the scarcity of high-quality evidence, fluoxetine (alone or in combination with CBT) seems to be the best choice for the acute treatment of moderate-to-severe depressive disorder in children and adolescents. However, the effects of these interventions might vary between individuals, so patients, carers, and clinicians should carefully balance the risk-benefit profile of efficacy, acceptability, and suicide risk of all active interventions in young patients with depression on a case-by-case basis. Funding: National Key Research and Development Program of China.

The lancet. Psychiatry · systematic review · 248 citationsread the source →

Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis.

Background: Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders. Methods: For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977). Findings: 83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis. Interpretation: There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed. Funding: Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.

The lancet. Psychiatry · meta-analysis · 309 citationsread the source →

Recruitment and retention rates in randomised controlled trials of exercise therapy in people with multimorbidity: a systematic review and meta-analysis.

Aim: To quantify recruitment, retention and differential retention rates and associated trial, participant and intervention characteristics in randomised controlled trials (RCTs) evaluating the effect of exercise therapy in people with multimorbidity. Data sources: MEDLINE, EMBASE, CINAHL and CENTRAL from 1990 to April 20, 2020. Study selection: RCTs including people with multimorbidity comparing exercise therapy with a non-exposed comparator group reporting at least one of the following outcomes: physical function, health-related quality of life, depression symptoms, or anxiety symptoms. Data extraction and synthesis: Recruitment rates (proportion of people randomised/proportion of people eligible), retention rates (proportion of people providing the outcomes of interest/proportion randomised) and differential retention rates (difference in proportion of people providing the outcomes in the intervention group and comparator group) were calculated. Meta-analysis using a random-effects model was used to estimate pooled proportions. Methodological quality was assessed using Cochrane ´Risk of Bias tool 2.0´ for individual studies, and the GRADE approach was used to assess the overall quality of the evidence. Results: Twenty-three RCTs with 3363 people were included. The pooled prevalence for recruitment rate was 75% (95%CI 66 to 84%). The pooled prevalence for retention rate was 90% (95%CI 86 to 94%) at the end of the intervention (12 weeks; interquartile range (IQR) (12 to 12)). Meta-regression analyses showed that increasing age and including a higher proportion of people with hypertension was associated with lower retention rates. Retention rates did not differ between the intervention and comparator groups. The overall quality of the evidence was deemed very low. Conclusion: Three in four eligible people with multimorbidity were randomised to RCTs using exercise therapy, of which nine out of 10 provided end of treatment outcomes with no difference seen between the intervention and comparison groups. However, the results must be interpreted with caution due to large differences between the included studies. Trial registration: ClinicalTrials.gov CRD42020161329 . Registered on 28 April 2020.

Trials · meta-analysis · 38 citationsread the source →

Effectiveness of a brief lay counsellor-delivered, problem-solving intervention for adolescent mental health problems in urban, low-income schools in India: a randomised controlled trial.

Background: Mental health problems are a leading cause of disability in adolescents worldwide. Problem solving is a well-tested mental health intervention in many populations. We aimed to investigate the effectiveness of a brief, transdiagnostic problem-solving intervention for common adolescent mental health problems when delivered by non-specialist school counsellors in New Delhi, India. Methods: This randomised trial was done in six government-run schools (three all-boys schools, two all-girls schools, and one co-educational school) that serve low-income communities. We recruited participants from grades 9 to 12 (ages 12-20 years) by selecting students with persistently elevated mental health symptoms accompanied by distress or functional impairment. Clinical eligibility criteria were assessed by research assistants using the Hindi-language version of the Strengths and Difficulties Questionnaire (SDQ), with reference to locally validated borderline cutoff scores of 19 or greater for boys and 20 or greater for girls on the SDQ Total Difficulties scale, an abnormal score of 2 or more on the SDQ Impact scale, and persistence of more than 1 month on the SDQ Chronicity index. Participants were randomly allocated (1:1) to problem solving delivered through a brief (2-3 week) counsellor-led intervention with supporting printed materials (intervention group), or problem solving delivered via printed booklets alone (control group). Primary outcomes were adolescent-reported mental health symptoms (SDQ Total Difficulties scale) and idiographic psychosocial problems (Youth Top Problems [YTP]) at 6 weeks. Primary analyses were done on an intention-to-treat basis at the 6-week endpoint. The trial is registered with ClinicalTrials.gov, NCT03630471. Findings: Participants were enrolled between Aug 20, and Dec 4, 2018. 283 eligible adolescents were referred to the trial, and 251 (89%) of these were enrolled (mean age 15·61 years; 174 [69%] boys). 125 participants were allocated to each group (after accounting for one participant in the intervention group who withdrew consent after randomisation). Primary outcome data were available for 245 (98%) participants. At 6 weeks, the mean YTP scores were 3·52 (SD 2·66) in the intervention group and 4·60 (2·75) in the control group (adjusted mean difference -1·01, 95% CI -1·63 to -0·38; adjusted effect size 0·36, 95% CI 0·11 to 0·61; p=0·0015). The mean SDQ Total Difficulties scores were 17·48 (5·45) in the intervention group and 18·33 (5·45) in the control group (-0·86, -2·14 to 0·41; 0·16, -0·09 to 0·41; p=0·18). We observed no adverse events. Interpretation: A brief lay counsellor-delivered problem-solving intervention combined with printed booklets seemed to have a modest effect on psychosocial outcomes among adolescents with diverse mental health problems compared with problem-solving booklets alone. This counsellor-delivered intervention might be a suitable first-line intervention in a stepped care approach, which is being evaluated in ongoing studies. Funding: Wellcome Trust.

The Lancet. Child & adolescent health · randomised controlled trial · 69 citationsread the source →

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

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

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

Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial.

Background: Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. Methods: In this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544. Findings: Between Jan 16, 2015, and May 31, 2017, we randomly assigned 368 patients to receive CBT plus standardised medical care (n=186) or standardised medical care alone (n=182); of whom 313 had primary outcome data at 12 months (156 [84%] of 186 patients in the CBT plus standardised medical care group and 157 [86%] of 182 patients in the standardised medical care group). At 12 months, no significant difference in monthly dissociative seizure frequency was identified between the groups (median 4 seizures [IQR 0-20] in the CBT plus standardised medical care group vs 7 seizures [1-35] in the standardised medical care group; estimated incidence rate ratio [IRR] 0·78 [95% CI 0·56-1·09]; p=0·144). Dissociative seizures were rated as less bothersome in the CBT plus standardised medical care group than the standardised medical care group (estimated mean difference -0·53 [95% CI -0·97 to -0·08]; p=0·020). The CBT plus standardised medical care group had a longer period of dissociative seizure freedom in the previous 6 months (estimated IRR 1·64 [95% CI 1·22 to 2·20]; p=0·001), reported better health-related quality of life on the EuroQoL-5 Dimensions-5 Level Health Today visual analogue scale (estimated mean difference 6·16 [95% CI 1·48 to 10·84]; p=0·010), less impairment in psychosocial functioning on the Work and Social Adjustment Scale (estimated mean difference -4·12 [95% CI -6·35 to -1·89]; p<0·001), less overall psychological distress than the standardised medical care group on the Clinical Outcomes in Routine Evaluation-10 scale (estimated mean difference -1·65 [95% CI -2·96 to -0·35]; p=0·013), and fewer somatic symptoms on the modified Patient Health Questionnaire-15 scale (estimated mean difference -1·67 [95% CI -2·90 to -0·44]; p=0·008). Clinical improvement at 12 months was greater in the CBT plus standardised medical care group than the standardised medical care alone group as reported by patients (estimated mean difference 0·66 [95% CI 0·26 to 1·04]; p=0·001) and by clinicians (estimated mean difference 0·47 [95% CI 0·21 to 0·73]; p<0·001), and the CBT plus standardised medical care group had greater satisfaction with treatment than did the standardised medical care group (estimated mean difference 0·90 [95% CI 0·48 to 1·31]; p<0·001). No significant differences in patient-reported seizure severity (estimated mean difference -0·11 [95% CI -0·50 to 0·29]; p=0·593) or seizure freedom in the last 3 months of the study (estimated odds ratio [OR] 1·77 [95% CI 0·93 to 3·37]; p=0·083) were identified between the groups. Furthermore, no significant differences were identified in the proportion of patients who had a more than 50% reduction in dissociative seizure frequency compared with baseline (OR 1·27 [95% CI 0·80 to 2·02]; p=0·313). Additionally, the 12-item Short Form survey-version 2 scores (estimated mean difference for the Physical Component Summary score 1·78 [95% CI -0·37 to 3·92]; p=0·105; estimated mean difference for the Mental Component Summary score 2·22 [95% CI -0·30 to 4·75]; p=0·084), the Generalised Anxiety Disorder-7 scale score (estimated mean difference -1·09 [95% CI -2·27 to 0·09]; p=0·069), and the Patient Health Questionnaire-9 scale depression score (estimated mean difference -1·10 [95% CI -2·41 to 0·21]; p=0·099) did not differ significantly between groups. Changes in dissociative seizures (rated by others) could not be assessed due to insufficient data. During the 12-month period, the number of adverse events was similar between the groups: 57 (31%) of 186 participants in the CBT plus standardised medical care group reported 97 adverse events and 53 (29%) of 182 participants in the standardised medical care group reported 79 adverse events. Interpretation: CBT plus standardised medical care had no statistically significant advantage compared with standardised medical care alone for the reduction of monthly seizures. However, improvements were observed in a number of clinically relevant secondary outcomes following CBT plus standardised medical care when compared with standardised medical care alone. Thus, adults with dissociative seizures might benefit from the addition of dissociative seizure-specific CBT to specialist care from neurologists and psychiatrists. Future work is needed to identify patients who would benefit most from a dissociative seizure-specific CBT approach. Funding: National Institute for Health Research, Health Technology Assessment programme.

The lancet. Psychiatry · randomised controlled trial · 192 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 →

Cost and Outcome of BehaviouRal Activation (COBRA): a randomised controlled trial of behavioural activation versus cognitive-behavioural therapy for depression.

Background: Depression is a common, debilitating and costly disorder. The best-evidenced psychological therapy - cognitive-behavioural therapy (CBT) - is complex and costly. A simpler therapy, behavioural activation (BA), may be an effective alternative. Objectives: To determine the clinical effectiveness and cost-effectiveness of BA compared with CBT for depressed adults at 12 and 18 months' follow-up, and to investigate the processes of treatments. Design: Randomised controlled, non-inferiority trial stratified by depression severity, antidepressant use and recruitment site, with embedded process evaluation; and randomisation by remote computer-generated allocation. Setting: Three community mental health services in England. Participants: Adults aged ≥ 18 years with major depressive disorder (MDD) recruited from primary care and psychological therapy services. Interventions: BA delivered by NHS junior mental health workers (MHWs); CBT by NHS psychological therapists. Outcomes: Primary: depression severity (as measured via the Patient Health Questionnaire-9; PHQ-9) at 12 months. Secondary: MDD status; number of depression-free days; anxiety (as measured via the Generalised Anxiety Disorder-7); health-related quality of life (as measured via the Short Form questionnaire-36 items) at 6, 12 and 18 months; and PHQ-9 at 6 and 18 months, all collected by assessors blinded to treatment allocation. Non-inferiority margin was 1.9 PHQ-9 points. We undertook intention-to-treat (ITT) and per protocol (PP) analyses. We explored cost-effectiveness by collecting direct treatment and other health- and social-care costs and calculating quality-adjusted life-years (QALYs) using the EuroQol-5 Dimensions, three-level version, at 18 months. Results: We recruited 440 participants (BA, n = 221; CBT, n = 219); 175 (79%) BA and 189 (86%) CBT participants provided ITT data and 135 (61%) BA and 151 (69%) CBT participants provided PP data. At 12 months we found that BA was non-inferior to CBT {ITT: CBT 8.4 PHQ-9 points [standard deviation (SD) 7.5 PHQ-9 points], BA 8.4 PHQ-9 points (SD 7.0 PHQ-9 points), mean difference 0.1 PHQ-9 points, 95% confidence interval (CI) -1.3 to 1.5 PHQ-9 points, p = 0.89; PP: CBT 7.9 PHQ-9 points (SD 7.3 PHQ-9 points), BA 7.8 PHQ-9 points (SD 6.5 PHQ-9 points), mean difference 0.0 PHQ-9 points, 95% CI -1.5 to 1.6 PHQ-9 points, p = 0.99}. We found no differences in secondary outcomes. We found a significant difference in mean intervention costs (BA, £975; CBT, £1235; p < 0.001), but no differences in non-intervention (hospital, community health, social care and medication costs) or total (non-intervention plus intervention) costs. Costs were lower and QALY outcomes better in the BA group, generating an incremental cost-effectiveness ratio of -£6865. The probability of BA being cost-effective compared with CBT was almost 80% at the National Institute for Health and Care Excellence's preferred willingness-to-pay threshold of £20,000-30,000 per QALY. There were no trial-related adverse events. Limitations: In this pragmatic trial many depressed participants in both groups were also taking antidepressant medication, although most had been doing so for a considerable time before entering the trial. Around one-third of participants chose not to complete a PP dose of treatment, a finding common in both psychotherapy trials and routine practice. Conclusions: We found that BA is as effective as CBT, more cost-effective and can be delivered by MHWs with no professional training in psychological therapies. Future work: Settings and countries with a paucity of professionally qualified psychological therapists, might choose to investigate the delivery of effective psychological therapy for depression without the need to develop an extensive and costly professional infrastructure. Trial registration: Current Controlled Trials ISRCTN27473954. 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. 46. See the NIHR Journals Library website for further project information.

Health technology assessment (Winchester, England) · randomised controlled trial · 28 citationsread the source →

The effects of volunteering on loneliness among lonely older adults: the HEAL-HOA dual randomised controlled trial.

Background: Previous randomised controlled trials have largely relied on self-reported volunteer work to assess the effects of volunteering and have rarely provided structured volunteering activities during the intervention period. The present study aimed to investigate the effects of social volunteering work over 12 months on loneliness among older adults during the COVID-19 pandemic. Methods: A dual randomised controlled trial was done in Hong Kong to investigate the long-term effects of telephone-delivered psychosocial interventions by older Chinese volunteers who were screened as lonely, for older adult recipients who had low income, lived alone, felt lonely, and were digitally excluded. Participants were included if they were aged 50-70 years; had provided consent to be trained and serve as a volunteer for at least 2 h per week for 6 months; had at least 3 years of secondary school education; had no severe self-reported physical, mental, or cognitive health problems; were not working full or part-time; had engaged in formal volunteering fewer than four times within the past year; and were lonely (ie, had a score of at least 6 on the three-item UCLA Loneliness Scale). Participants were allocated into either the volunteering or control group (psychoeducation programme) using a random number method. The details of group allocation were concealed as the research assistant responsible for randomisation was different to the research assistants responsible for recruitment and assessments (who were masked to the condition). Following a 6-week training, the volunteers delivered a psychosocial intervention to older intervention recipients for 6 months. The primary outcome was loneliness measured with the 20-item UCLA Loneliness Scale and the De Jong Gierveld (DJG) Loneliness Scales at 6 months and 12 months. Assessments were performed before training (baseline; T1), at 6 months (T2), and at 12 months after training (T3). The intention-to-treat principle was used to compare the effects of volunteering between the two groups. The trial was registered in the Clinical Trials Registry of the University of Hong Kong Clinical Trials Centre (HKUCTR-2929). This trial has completed. Findings: Between May 3, 2021, and Oct 6, 2022, a total of 375 individuals were recruited to the trial, including 84 males (22%) and 291 females (78%). 185 were randomly assigned to the volunteering group (56 to deliver a mindfulness intervention, 65 to deliver a behavioural activation intervention, and 64 to deliver a befriending intervention) and 190 were assigned to the control group. 311 (83%) of 375 participants were 60 years or older (median 64 years [SD 4·86]). Participants in the volunteering group reported a significantly lower level of loneliness at T2 (dppc2 ranged from -0·41 to -0·70) compared with T1 than participants in the control condition. There was a significant decrease in loneliness measured using the UCLA Loneliness Scale at T2 in the volunteering group but such a decline was not shown in the control group (condition × time interaction, estimate 0·19 [95% CI 0·08 to 0·29], p=0·00058, dppc2=-0·41). Similarly, when measured with the DJG Loneliness Scale, there was a significantly greater decrease in loneliness in the volunteering group compared with the control group at T2, including a medium to large effect size on total DJG scores (estimate 1·34 [95% CI 0·83 to 1·84], p<0·0001, dppc2=-0·70) and a medium effect size on emotional (estimate 0·63 [0·35 to 0·90], p<0·0001, dppc2=-0·59) and social subscales (estimate 0·71 [95% CI 0·37 to 1·05], p<0·0001, dppc2=-0·58). Although most of the positive effects of volunteering were not sustained at T3, the volunteers who continued to volunteer for more than 2 h per week at T3 reported lower levels of loneliness than those who did not maintain volunteering. Interpretation: This randomised controlled trial demonstrates the beneficial effect of volunteering on reducing loneliness in older adults who feel lonely, and that this benefit can be maintained through continued participation in voluntary work. Future intervention programmes should strengthen older adults' commitment to volunteer. Funding: Research Grants Committee of the Hong Kong Special Administrative Region, China.

The lancet. Healthy longevity · randomised controlled trial · 16 citationsread the source →

Interventions targeting social isolation in older people: a systematic review.

Background: Targeting social isolation in older people is a growing public health concern. The proportion of older people in society has increased in recent decades, and it is estimated that approximately 25% of the population will be aged 60 or above within the next 20 to 40 years. Social isolation is prevalent amongst older people and evidence indicates the detrimental effect that it can have on health and wellbeing. The aim of this review was to assess the effectiveness of interventions designed to alleviate social isolation and loneliness in older people. Methods: Relevant electronic databases (MEDLINE, EMBASE, ASSIA, IBSS, PsycINFO, PubMed, DARE, Social Care Online, the Cochrane Library and CINAHL) were systematically searched using an extensive search strategy, for randomised controlled trials and quasi-experimental studies published in English before May 2009. Additional articles were identified through citation tracking. Studies were included if they related to older people, if the intervention aimed to alleviate social isolation and loneliness, if intervention participants were compared against inactive controls and, if treatment effects were reported. Two independent reviewers extracted data using a standardised form. Narrative synthesis and vote-counting methods were used to summarise and interpret study data. Results: Thirty two studies were included in the review. There was evidence of substantial heterogeneity in the interventions delivered and the overall quality of included studies indicated a medium to high risk of bias. Across the three domains of social, mental and physical health, 79% of group-based interventions and 55% of one-to-one interventions reported at least one improved participant outcome. Over 80% of participatory interventions produced beneficial effects across the same domains, compared with 44% of those categorised as non-participatory. Of interventions categorised as having a theoretical basis, 87% reported beneficial effects across the three domains compared with 59% of interventions with no evident theoretical foundation. Regarding intervention type, 86% of those providing activities and 80% of those providing support resulted in improved participant outcomes, compared with 60% of home visiting and 25% of internet training interventions. Fifty eight percent of interventions that explicitly targeted socially isolated or lonely older people reported positive outcomes, compared with 80% of studies with no explicit targeting. Conclusions: More, well-conducted studies of the effectiveness of social interventions for alleviating social isolation are needed to improve the evidence base. However, it appeared that common characteristics of effective interventions were those developed within the context of a theoretical basis, and those offering social activity and/or support within a group format. Interventions in which older people are active participants also appeared more likely to be effective. Future interventions incorporating all of these characteristics may therefore be more successful in targeting social isolation in older people.

BMC public health · systematic review · 395 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 →

Antenatal mindfulness intervention to reduce depression, anxiety and stress: a pilot randomised controlled trial of the MindBabyBody program in an Australian tertiary maternity hospital

BACKGROUND: Mindfulness interventions to reduce psychological distress are well-suited to pregnancy, due to their brief and non-pharmacological nature, but there is a need for more robust evidence determining their usefulness. This pilot study was designed to explore the feasibility of a randomised controlled trial of a mindfulness intervention to reduce antenatal depression, anxiety and stress. METHODS: The study was designed in two parts 1) a non-randomised trial targeting women at risk of mental health problems (a selected population) and 2) a randomised controlled trial (RCT) of a universal population. Process evaluation focused on feasibility of recruitment pathways, participant retention, acceptability of study measures, and engagement with mindfulness practices. Measurement of psychological distress was taken pre and post intervention through the Centre for Epidemiologic Studies Depression Scale Revised, the Depression Anxiety and Stress Scale-21, the State-Trait Anxiety Inventory, and the Perceived Stress Scale. RESULTS: 20 women were recruited to the non-randomised trial, and 32 to the RCT. Recruitment through a mailed study brochure at the time of booking-in to the hospital resulted in the largest number of participants in the RCT (16/32; 50%), and resulted in considerably earlier recruitment (50% in first trimester, 50% second trimester) compared to recruitment through the antenatal clinic waiting room (86% in second trimester, 14% third trimester). Over a third of women in the universal population scored above clinical cut-offs for depression and anxiety, indicating a sample with more symptomology than the general population. The most common reason for loss to follow-up was delivery of baby prior to follow-up (n = 9). In the non-randomised study, significant within group improvements to depression and anxiety were observed. In the intervention arm of the RCT there were significant within group improvements to anxiety and mindfulness. No between group differences for the intervention and 'care as usual' control group were observed. CONCLUSIONS: This small pilot study provides evidence on the feasibility of an antenatal mindfulness intervention to reduce psychological distress. Major challenges include: finding ways to facilitate recruitment in early pregnancy and engaging younger women and other vulnerable populations. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000742774 (31/10/2012).

BMC Pregnancy and Childbirth · randomised controlled trial · 221 citationsread the source →

Miller Early Childhood Sustained Home-visiting (MECSH) trial: design, method and sample description.

Background: Home visiting programs comprising intensive and sustained visits by professionals (usually nurses) over the first two years of life show promise in promoting child health and family functioning, and ameliorating disadvantage. Australian evidence of the effectiveness of sustained nurse home visiting in early childhood is limited. This paper describes the method and cohort characteristics of the first Australian study of sustained home visiting commencing antenatally and continuing to child-age two years for at-risk mothers in a disadvantaged community (the Miller Early Childhood Sustained Home-visiting trial). Methods and design: Mothers reporting risks for poorer parenting outcomes residing in an area of socioeconomic disadvantage were recruited between February 2003 and March 2005. Mothers randomised to the intervention group received a standardised program of nurse home visiting. Interviews and observations covering child, maternal, family and environmental issues were undertaken with mothers antenatally and at 1, 12 and 24 months postpartum. Standardised tests of child development and maternal-child interaction were undertaken at 18 and 30 months postpartum. Information from hospital and community heath records was also obtained. Discussion: A total of 338 women were identified and invited to participate, and 208 were recruited to the study. Rates of active follow-up were 86% at 12 months, 74% at 24 months and 63% at 30 months postpartum. Participation in particular data points ranged from 66% at 1 month to 51% at 24 months postpartum. Rates of active follow-up and data point participation were not significantly different for the intervention or comparison group at any data point. Mothers who presented for antenatal care prior to 20 weeks pregnant, those with household income from full-time employment and those who reported being abused themselves as a child were more likely to be retained in the study. The Miller Early Childhood Sustained Home-visiting trial will provide Australian evidence of the effectiveness of sustained nurse home visiting for children at risk of poorer health and developmental outcomes. Trial registration: ACTRN12608000473369.

BMC public health · randomised controlled trial · 33 citationsread the source →

Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study.

Background: Telomere shortness in human beings is a prognostic marker of ageing, disease, and premature morbidity. We previously found an association between 3 months of comprehensive lifestyle changes and increased telomerase activity in human immune-system cells. We followed up participants to investigate long-term effects. Methods: This follow-up study compared ten men and 25 external controls who had biopsy-proven low-risk prostate cancer and had chosen to undergo active surveillance. Eligible participants were enrolled between 2003 and 2007 from previous studies and selected according to the same criteria. Men in the intervention group followed a programme of comprehensive lifestyle changes (diet, activity, stress management, and social support), and the men in the control group underwent active surveillance alone. We took blood samples at 5 years and compared relative telomere length and telomerase enzymatic activity per viable cell with those at baseline, and assessed their relation to the degree of lifestyle changes. Findings: Relative telomere length increased from baseline by a median of 0·06 telomere to single-copy gene ratio (T/S)units (IQR-0·05 to 0·11) in the lifestyle intervention group, but decreased in the control group (-0·03 T/S units, -0·05 to 0·03, difference p=0·03). When data from the two groups were combined, adherence to lifestyle changes was significantly associated with relative telomere length after adjustment for age and the length of follow-up (for each percentage point increase in lifestyle adherence score, T/S units increased by 0·07, 95% CI 0·02-0·12, p=0·005). At 5 years, telomerase activity had decreased from baseline by 0·25 (-2·25 to 2·23) units in the lifestyle intervention group, and by 1·08 (-3·25 to 1·86) units in the control group (p=0·64), and was not associated with adherence to lifestyle changes (relative risk 0·93, 95% CI 0·72-1·20, p=0·57). Interpretation: Our comprehensive lifestyle intervention was associated with increases in relative telomere length after 5 years of follow-up, compared with controls, in this small pilot study. Larger randomised controlled trials are warranted to confirm this finding. Funding: US Department of Defense, NIH/NCI, Furlotti Family Foundation, Bahna Foundation, DeJoria Foundation, Walton Family Foundation, Resnick Foundation, Greenbaum Foundation, Natwin Foundation, Safeway Foundation, Prostate Cancer Foundation.

The Lancet. Oncology · cohort or longitudinal · 252 citationsread the source →

Analysis of persistent organic pollutants in marine sediments using a novel microwave assisted solvent extraction and liquid-phase microextraction technique.

A simple and novel analytical method for quantifying persistent organic pollutants (POPs) in marine sediments has been developed using microwave assisted solvent extraction (MASE) and liquid-phase microextraction (LPME) using hollow fibre membrane (HFM). POPs studied included twelve organochlorine pesticides (OCP) and eight polychlorinated biphenyl (PCB) congeners. MASE was used for the extraction of POPs from 1 g of sediment using 10 ml of ultrapure water at 600 W for 20 min at 80 degrees C. The extract was subsequently subjected to a single step LPME-HFM cleanup and enrichment procedure. Recovery varied between 73 and 111% for OCPs; and 86-110% for PCBs, and exceeded levels achieved for conventional multi-step Soxhlet extraction coupled with solid-phase extraction. The method detection limit for each POP analyte ranged from 0.07 to 0.70 ng g(-1), and peak areas were proportional to analyte concentrations in the range of 5-500 ng g(-1). Relative standard deviations of less than 20% was obtained, based on triplicate sample analysis. The optimized technique was successfully applied to POP analysis of marine sediments collected from the northeastern and southwestern areas of Singapore's coastal environment.

Journal of chromatography. A · cohort or longitudinal · 54 citationsread the source →

Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR).

Unlabelled: The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. Methods: The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. Results: Mean age was 55 ± 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (≥40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm³. The median FENO was 26 ppb (IQR: 15-43) and 22% of SA had FENO ≥ 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos ≥ 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu ≥ 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT < 20 and 77% with ACQ > 1.5. Conclusion: In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies.

Respiratory medicine · cohort or longitudinal · 199 citationsread the source →

Deconstructing the Complexities of Advance Care Planning Outcomes: What Do We Know and Where Do We Go? A Scoping Review.

Background/objectives: Advance care planning (ACP) has shown benefit in some, but not all, studies. It is important to understand the utility of ACP. We conducted a scoping review to identify promising interventions and outcomes. Design: Scoping review. Measurements: We searched MEDLINE/PubMed, EMBASE, CINAHL, PsycINFO, and Web of Science for ACP randomized controlled trials from January 1, 2010, to March 3, 2020. We used standardized Preferred Reporting Items for Systematic Review and Meta-Analyses methods to chart study characteristics, including a standardized ACP Outcome Framework: Process (e.g., readiness), Action (e.g., communication), Quality of Care (e.g., satisfaction), Health Status (e.g., anxiety), and Healthcare Utilization. Differences between arms of P < .05 were deemed positive. Results: Of 1,464 articles, 69 met eligibility; 94% were rated high quality. There were variable definitions, age criteria (≥18 to ≥80 years), diseases (e.g., dementia and cancer), and settings (e.g., outpatient and inpatient). Interventions included facilitated discussions (42%), video only (20%), interactive, multimedia (17%), written only (12%), and clinician training (9%). For written only, 75% of primary outcomes were positive, as were 69% for multimedia programs; 67% for facilitated discussions, 59% for video only, and 57% for clinician training. Overall, 72% of Process and 86% of Action outcomes were positive. For Quality of Care, 88% of outcomes were positive for patient-surrogate/clinician congruence, 100% for patients/surrogate/clinician satisfaction with communication, and 75% for surrogate satisfaction with patients' care, but not for goal concordance. For Health Status outcomes, 100% were positive for reducing surrogate/clinician distress, but not for patient quality of life. Healthcare Utilization data were mixed. Conclusion: ACP is complex, and trial characteristics were heterogeneous. Outcomes for all ACP interventions were predominantly positive, as were Process and Action outcomes. Although some Quality of Care and Health Status outcomes were mixed, increased patient/surrogate satisfaction with communication and care and decreased surrogate/clinician distress were positive. Further research is needed to appropriately tailor interventions and outcomes for local contexts, set appropriate expectations of ACP outcomes, and standardize across studies.

Journal of the American Geriatrics Society · review · 381 citationsread the source →

The acute efficacy of antipsychotics in schizophrenia: a review of recent meta-analyses.

Schizophrenia is the eighth leading cause of disability worldwide in people aged 15-44 years. Before antidopaminergic antipsychotics were introduced in the 1950s, no effective medications existed for the treatment of schizophrenia. This review summarizes key meta-analytic findings regarding antipsychotic efficacy in the acute treatment of schizophrenia, including clozapine in treatment-resistant patients. In the most comprehensive meta-analysis of randomized controlled trials conducted in multi-episode schizophrenia, antipsychotics outperformed placebo regarding total symptoms, positive symptoms, negative symptoms, depressive symptoms, quality of life and social functioning. Amongst these outcomes, the standardized mean difference for overall symptoms was largest, that is, 0.47 (95% credible interval = 0.42-0.51), approaching a medium effect size, being reduced to 0.38 when publication bias and small-trial effects were accounted for. A comparison of two meta-analyses indicated that first-episode patients, compared with multi-episode patients, were more likely to have at least minimal treatment response [⩾20% Positive and Negative Syndrome Scale (PANSS)/Brief Psychiatric Rating Scale (BPRS) score reduction: 81% versus 51%] and good response (⩾50% PANSS/BPRS score reduction: 52% versus 23%). In multi-episode schizophrenia, no response or worsening after 2 weeks of a therapeutic antipsychotic dose was highly predictive of not achieving a good response at endpoint (median treatment = 6 weeks: specificity = 86%; positive predictive value = 90%), suggesting a change in treatment should be considered in such cases. In first-episode psychosis, adequately dosed antipsychotic treatment trials for more than 2 weeks are recommended before using no response or worsening as a decision point for aborting a given antipsychotic. In clearly defined treatment-resistant schizophrenia, clozapine generally outperformed other antipsychotics, especially when dosed appropriately (target = 3-6 months' duration; trough clozapine level ⩾350-400 μg/L) with a response rate (⩾20% PANSS/BPRS) of 33% by 3 months of treatment. High antipsychotic doses and psychotropic combinations are unlikely to be superior to standard doses of antipsychotic monotherapy. Acute antipsychotic efficacy in schizophrenia depends on the targeted symptom domain (greater efficacy: total and positive symptoms, lesser efficacy: negative symptoms, depressive symptoms, social functioning and quality of life). Greater antipsychotic efficacy is associated with higher total baseline symptom severity, treatment-naïveté/first-episode status, shorter illness duration, and trials that are nonindustry sponsored and that have a lower placebo effect. The heterogeneity of antipsychotic response across individuals and key symptom domains, the considerable degree of nonresponse/treatment resistance in multi-episode patients, and the adverse effect potential of antipsychotics are major limitations, underscoring the need to develop new medications for the treatment of schizophrenia. Drug development should include matching patient subgroups, which are identified by means of clinical and biomarker variables, to mechanisms of action of novel medications, targeting specific symptom domains, and investigating mechanisms of action other than dopaminergic blockade.

Therapeutic advances in psychopharmacology · review · 154 citationsread the source →

Review: Adult Outcome as Seen Through Controlled Prospective Follow-up Studies of Children With Attention-Deficit/Hyperactivity Disorder Followed Into Adulthood.

Objective: To describe adult outcome of people with attention-deficit/hyperactivity disorder (ADHD) diagnosed in childhood and its several key predictors via a review of 7 North American controlled prospective follow-up studies: Montreal, New York, Milwaukee, Pittsburgh, Massachusetts General Hospital (MGH), Berkeley, and 7-site Multimodal Treatment Study of Children With ADHD (MTA). Method: All studies were prospective and followed children with a diagnosis of ADHD and an age- and gender-matched control group at regular intervals from childhood (6-12 years of age) through adolescence into adulthood (20-40 years of age), evaluating symptom and syndrome persistence, functional outcomes, and predictors of these outcomes. Results: The rates of ADHD syndrome persistence ranged from 5.7% to 77%, likely owing to varying diagnostic criteria and the source of information (self-report vs informant report) across the studies. However, all studies observed high rates of symptomatic persistence ranging from 60% to 86%. The 7 studies were largely consistent in finding that relative to control groups, research participants with childhood-diagnosed ADHD had significant impairments in the areas of educational functioning, occupational functioning, mental health, and physical health as well as higher rates of substance misuse, antisocial behavior, and unsafe driving. The most consistently observed predictors of functional outcomes included ADHD persistence and comorbidity, especially with disruptive behavior disorders. Conclusion: Childhood ADHD has high rates of symptomatic persistence, which is associated with negative functional outcomes. Characteristics that predict these negative outcomes, such as comorbid disruptive behavior disorders, may be important targets for intervention.

Journal of the American Academy of Child and Adolescent Psychiatry · review · 82 citationsread the source →

Patients with premenstrual dysphoric disorder have increased startle response across both cycle phases and lower levels of prepulse inhibition during the late luteal phase of the menstrual cycle.

Patients with premenstrual dysphoric disorder (PMDD) experience their most intense symptoms during the late luteal phase. The aim of the current study was to compare acoustic startle response and prepulse inhibition in PMDD patients and controls during the follicular and late luteal phases of the menstrual cycle. Following two months of prospective daily ratings on the Cyclicity Diagnoser scale, 30 PMDD patients and 30 asymptomatic controls, between the ages of 20 and 46, were included in the study. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of m. orbicularis oculi. Twenty pulse-alone trials (115 dB 40 ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115 dB 40 ms noise burst preceded at a 100 ms interval by 20 ms prepulses that were 72, 74, 78, or 86 dB. PMDD patients had a significantly higher startle response than controls during both phases of the menstrual cycle (p<0.05). PMDD patients exhibited lower levels of prepulse inhibition with 78 dB and 86 dB prepulses compared to control subjects in the luteal (p<0.01) but not in the follicular phase. Whereas control subjects displayed increased PPI during the late luteal phase compared to the follicular phase (p<0.01), PPI magnitude remained unchanged in PMDD patients between cycle phases. Relative to controls, PMDD patients displayed increased startle reactivity across both menstrual cycle phases and deficits in prepulse inhibition of acoustic startle during the late luteal phase. These findings are consistent with an altered response to ovarian steroids among PMDD patients.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 39 citationsread the source →

Pregnancy in Adolescence - A Challenge Beyond Public Health Policies

Recent Sustainable Development Goals were established by the United Nations (2015–2030), including the broad goal of “good health and wellbeing” for all. Good health and wellbeing (item 3), quality education (item 4), gender equality (item 5) and reduced inequalities (item 10) are among the 17 items of the list.[ 1 ] These four cited goals are directly linked to the unresolved issue of pregnancy during adolescence, and point to fact that well-directed work needs to be done in this area. According to the United Nations Population Fund (UNFPA), around 16 million girls between the ages of 15 and 19, and 1 million girls under the age of 15, give birth every year around the world. In addition, ∼ 95% of these deliveries are concentrated in developing countries, and it is estimated that by 2035 births will be ∼ 20 million, making pregnancy in adolescence one of the major public health problems.[ 2 ] [ 3 ] In Brazil, the 2015 National Household Sample Program (PNAD, in the Portuguese acronym) compared the specific fertility rate of women aged 15 to 19 between the years of 2004 and 2014, and this indicator changed from 78.8 to 60.5 children per thousand women in this age group. The participation of adolescents in the total fertility rate remained high, going from 18.4 to 17.4% in the same period.[ 4 ] Maternity during adolescence draws attention to political debates and issues that have been studied in different areas of knowledge. In the area of public health, teenage pregnancy is considered a major problem due to the high prevalence and perinatal risks. Adolescent pregnancies may be considered high risk, especially those of adolescents under the age of 15, and they often fall outside the statistics data.[ 5 ] Childbirth and complications of pregnancy are the leading causes of hospitalization and death among adolescent women in developing countries. Anemia, preeclampsia and postpartum hemorrhage may occur in greater proportions than in adult pregnant women.[ 6 ] A recent study among pregnant Brazilian adolescents found that 42% of them suffered from anemia.[ 7 ] Preterm birth, low birth weight, low Apgar score and perinatal mortality are also more frequent among the children of teenagers.[ 6 ] The nutritional aspects should also be considered a problem in the association of gestation with adolescence, since these are two periods of great metabolic transformations overlapping. Adolescents in general present an accelerated increase in their overall metabolism, and often have poor nutritional habits and make poor food choices, a behavior that generates deficiencies in the intake of some micronutrients, higher rates of overweight and obesity, in addition to a greater frequency of pathological eating disorders, such as bulimia and anorexia.[ 8 ] Obesity may be associated with early menarche, which is one of the risk factors for early pregnancy. During pregnancy, teenagers can experiment excessive gestational weight gain, and that may result in post-pregnancy weight retention and obesity in adult life. Overweightness and obesity affect ∼ 30–40% of Brazilian women in reproductive age with physical and psychological repercussions leading to an increased risk of non-communicable diseases and a cycle of morbidity and poor health condition in the broadest sense.[ 9 ] [ 10 ] [ 11 ] [ 12 ] Besides the aforementioned medical risks, there is an increase in the social risk related to the physical, emotional, economic, and social dependence of these girls. There is also a greater risk of violence, in all its forms, associated with the lack of autonomy of these mothers in making their own decisions. Lack of autonomy can compromise the aspects related to the evolution of the gestation, as well as various aspects of the mother's future life. Examples of this condition include the later onset of prenatal follow-up,[ 6 ] and the higher prevalence of “delays” in obstetric care, related to the occurrence of maternal near miss, both of which are higher among adolescents.[ 13 ] Unwanted pregnancy is an important cause of morbidity in adolescence, and the use of effective contraception is one of the fundamental pillars that prevent the occurrence of this problem.[ 14 ] In the United States, teenage pregnancy rates are the highest among high-income countries.[ 15 ] However, there has been a reduction since 1990, which could be associated with educational programs that address responsible sexuality and contraceptive use among adolescents. Such educational programs would have been responsible for 86% of this decline.[ 16 ] The use of a “double method” or “double protection,” which consists of the use of a condom associated with another effective method, and a more widespread use of long-acting reversible contraceptives (LARCs) accompanied this reduction.[ 17 ] Any reversible method of contraception can be used for adolescents. Neither the age nor the number of previous pregnancies constitutes a medical reason to contraindicate any of them. It is important to remember that, whatever the choice, it should be based on current scientific information, respecting the eligibility criteria of each method established by the World Health Organization (WHO) and the recommendations of the Brazilian Ministry of Health.[ 18 ] [ 19 ] A Brazilian study shows that after childbirth, the most used contraceptive method was depot medroxyprogesterone acetate (DMPA). To improve contraception and reduce the chance of unintended pregnancies among adolescents, we should promote the use of LARCs.[ 20 ] A recent systematic review of the Cochrane Library compiled studies with a higher quality of information elaboration and consistency, and concluded that it is necessary to integrate educational interventions and offer contraceptive methods in order to reduce the phenomenon of teenage pregnancy.[ 21 ] The abstention from formal education among adolescent pregnant women is relevant, and many of them do not have the opportunity to resume their education once they give birth due to the time they spend in the care of their newborns.[ 22 ] The lower schooling of adolescents at the time of their first pregnancy can be attributed to this serious condition of social deprivation (dropping out of school), and could be one of the reasons behind the etiology of the problem, being the cause, and not the consequence. Disruption of studies in the puerperal period are often unavoidable due to lack of support for these girls and their babies. This all adds to the negative social and economic impact on the adolescents, their families, and society as a whole, for it hinders them from using their potential to invest in their education, find a job and ear an income. The absence from school also increases the chances of a recurring pregnancy still during adolescence. On the other hand, adolescents who do not become pregnant are more likely to finish high school.[ 22 ] In addition to formal education, adolescent sexual education is required. It is widely quoted by the WHO / and The Joint United Nations Program on HIV/AIDS (UNAIDS) that “Sexual education does not lead to increased sexual activity or stimulation of early sexual activity,” and a sexual orientation and education policy is necessary to enable “educated and empowered women and girls to make decisions about their own health,” thereby ensuring their reproductive rights, according to Dr. Margaret Chan, Director-General of the WHO. In this context, the role of the gynecologist-obstetrician is to guide and ensure safe and effective contraception and protection from sexually transmitted diseases. For pregnant teenagers, they could perform prenatal care, preferably with a multidisciplinary team composed of motivated professionals aiming at pregnancy care, as well as health promotion in the general sense. In the puerperal period, it is necessary to pay special attention to contraception, because the risk of another pregnancy is greater then. It is also important to recruit all possible support, so that these young mothers can resume their life plans. More than an organic look at the risks involved in gestation among adolescents, the meaning of pregnancy varies according to the social context in which the teenager is inserted. The restricted perspective of personal growth by these young women, the lack of educational incentive and labor market, make them find in pregnancy and in the social role of being a mother a life goal. In this sense, it is perceived that dealing with the reality of pregnancy in adolescence involves dealing with contradictions and ethical dilemmas that go beyond the clinical protocols of care. Adolescent pregnancy requires critical insight. It is a public health problem, and it presents different dimensions as a human and social phenomenon in different cultures, but its occurrence can often disrupt personal growth and development, and jeopardize future opportunities for many girls. Finally, it is a question of gender and vulnerability that reflects all kinds of inequity.

Revista Brasileira Ginecologia e Obstetrícia · editorial or comment · 27 citationsread the source →

Cortisol slopes and conflict: A spouse's perceived stress matters.

Background: Perceived stress can lead to dysregulated cortisol patterns, including blunted peaks and flatter slopes, which are associated with increased morbidity and mortality risks. Couples' interdependence provides a prime opportunity for partners' stress to disrupt a healthy cortisol pattern. This study examined how individuals' own perceived stress and their partners' perceived stress shape cortisol levels and slopes across the day, as well as how positive and negative behaviors during conflict discussions impact associations between stress and cortisol. Methods: Both partners of a married couple (n = 43 couples, 86 individuals) completed a full day in-person visit. Each partner completed the Perceived Stress Scale, and all couples engaged in a 20-min marital problem discussion which was recorded and later coded for positive and negative behaviors using the Rapid Marital Interaction Coding System (RMICS). Partners also provided five salivary cortisol samples across the day, two samples before the conflict and three after the conflict. The dyadic design and analyses provided a way to account for the interdependent nature of married couples' data, as well as to use the Actor-Partner Interdependence Model (APIM) to assess the mutual influence of spouses' stress on cortisol. Results: Individuals with more stressed partners had flatter cortisol slopes than individuals with less stressed partners, who showed steeper and thus healthier declines across the day. Individuals' cortisol levels at the beginning of the day were similar regardless of their partners' perceived stress, but individuals with more stressed partners had higher cortisol levels 30-min, 1 h, and 4 h after the conflict discussion than those with less stressed partners. Couples' behavior during the conflict moderated the relationship between partner perceived stress and average cortisol; when couples used more negative and less positive behaviors, individuals with more stressed partners had higher average cortisol levels than those with less stressed partners. Conclusion: On a day couples experienced conflict, having a partner with higher perceived stress is associated with dysregulated cortisol patterns, including higher levels and flatter slopes, but having a partner with lower perceived stress is linked to steeper and thus healthier cortisol declines. A partner's stress was particularly consequential for one's own cortisol when couples used more negative and fewer positive behaviors during a conflict discussion. This research adds to the growing literature on pathways connecting marital interactions to important biorhythms and health.

Psychoneuroendocrinology · 14 citationsread the source →

Most plant-based meat alternative buyers also buy meat: an analysis of household demographics, habit formation, and buying behavior among meat alternative buyers.

The promise of novel plant-based meat alternatives (PBMAs) to lessen the health and environmental impacts of meat consumption ultimately depend on market acceptance and the extent to which they displace meat in consumers' diets. We use household scanner data to provide an in-depth analysis of consumers' PBMA buying behaviors. PBMAs buyers tend to be young, single, female, college educated, employed, higher income, and non-white. About 20% of consumers purchased a PBMA at least once, and 12% purchased a PBMA on multiple occasions. About 2.79% of households only purchased PBMAs. About 86% of PBMA buyers also bought ground meat; however, PBMA buyers spent about 13% less on ground meat. Interestingly, after a household's first PBMA purchase, ground meat consumption did not fall. The number of households buying a PBMA for the first time fell over the two year period studied, despite the increase in market share in the ground meat market.

Scientific reports · 28 citationsread the source →

Changes in heart rate and blood pressure during nocturnal hot flashes associated with and without awakenings.

Hot flashes (HFs) are a hallmark of menopause in midlife women. They are beyond bothersome symptoms, having a profound impact on quality of life and wellbeing, and are a potential marker of cardiovascular (CV) disease risk. Here, we investigated the impact on CV functioning of single nocturnal HFs, considering whether or not they were accompanied by arousals or awakenings. We investigated changes in heart rate (HR, 542 HFs), blood pressure (BP, 261 HFs), and pre-ejection period (PEP, 168 HFs) across individual nocturnal physiological HF events in women in the menopausal transition or post-menopause (age: 50.7 ± 3.6 years) (n = 86 for HR, 45 for BP, 27 for PEP). HFs associated with arousals/awakenings (51.1%), were accompanied by an increase in systolic (SBP; ~6 mmHg) and diastolic (DBP; ~5 mmHg) BP and HR (~20% increase), sustained for several minutes. In contrast, HFs occurring in undisturbed sleep (28.6%) were accompanied by a drop in SBP and a marginal increase in HR, likely components of the heat dissipation response. All HFs were accompanied by decreased PEP, suggesting increased cardiac sympathetic activity, with a prolonged increase for HFs associated with sleep disruption. Older age predicted greater likelihood of HF-related sleep disturbance. HFs were less likely to wake a woman in rapid-eye-movement and slow-wave sleep. Findings show that HFs associated with sleep disruption, which are in the majority and more likely in older women, lead to increases in HR and BP, which could have long-term impact on nocturnal CV restoration in women with multiple HFs.

Sleep · 12 citationsread the source →

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

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

The Lancet. Planetary health · 9 citationsread the source →

Optimizing the clinical utility of four proposed criteria for a persistent and impairing grief disorder by emphasizing core, rather than associated symptoms.

Background: Distinguishing a disorder of persistent and impairing grief from normative grief allows clinicians to identify this often undetected and disabling condition. As four diagnostic criteria sets for a grief disorder have been proposed, their similarities and differences need to be elucidated. Methods: Participants were family members bereaved by US military service death (N = 1732). We conducted analyses to assess the accuracy of each criteria set in identifying threshold cases (participants who endorsed baseline Inventory of Complicated Grief ⩾30 and Work and Social Adjustment Scale ⩾20) and excluding those below this threshold. We also calculated agreement among criteria sets by varying numbers of required associated symptoms. Results: All four criteria sets accurately excluded participants below our identified clinical threshold (i.e. correctly excluding 86-96% of those subthreshold), but they varied in identification of threshold cases (i.e. correctly identifying 47-82%). When the number of associated symptoms was held constant, criteria sets performed similarly. Accurate case identification was optimized when one or two associated symptoms were required. When employing optimized symptom numbers, pairwise agreements among criteria became correspondingly 'very good' (κ = 0.86-0.96). Conclusions: The four proposed criteria sets describe a similar condition of persistent and impairing grief, but differ primarily in criteria restrictiveness. Diagnostic guidance for prolonged grief disorder in International Classification of Diseases, 11th Edition (ICD-11) functions well, whereas the criteria put forth in Section III of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are unnecessarily restrictive.

Psychological medicine · 29 citationsread the source →

Developing a smartphone application to support social connectedness and wellbeing in young people with cystic fibrosis.

Background: Young people with cystic fibrosis (CF) may be at increased risk of social isolation and mental illness. This study aimed to design and evaluate the usability and acceptability of a smartphone application (app) to support the social connectedness and wellbeing of young people living with CF. Methods: Young people with CF aged 12-17 years (N = 22) were recruited from two paediatric hospitals in Australia. Study participants tested the CF app for six weeks before responding to an online survey about the app's usability and acceptability. A subsample of participants (n = 20) discussed the app's strengths and weaknesses during 11 online group interviews. Results: During the six-week testing period, 77% of participants used the app at least once a week and 82% accessed the app from a smartphone. Usability of the CF app was rated high. Most participants agreed the app was easy to use (86%) and felt comfortable using it (96%). Acceptability of the app was moderate. 77% of participants agreed they would recommend the app to others. Recommendations to improve the app's functionality and acceptability included locating the chatroom within the app rather than redirecting users to a web browser and allowing users to personalise images, wellness tips and videos. Conclusions: This study developed and tested a highly usable, and moderately acceptable, smartphone app to improve the psychosocial health of young people living with CF. Future research will test the efficacy of the CF app on users' social connectedness and wellbeing.

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 15 citationsread the source →

Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.

Background: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. Methods: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Findings: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). Interpretation: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Funding: Gates Foundation and Bloomberg Philanthropies.

Lancet (London, England) · 257 citationsread the source →

Impaired survival and long-term neurological problems in benign meningioma.

Purpose: To assess long-term functional outcome and survival among patients with meningioma World Health Organization (WHO) grade I. Methods: Retrospective analysis of 205 patients after resection of WHO grade I intracranial meningioma from 1985 through 2003. Expected age- and sex-specific survival was calculated by applying Dutch life-table statistics to each patient for the individual duration of follow-up. Long-term functional outcome was assessed using a mailed questionnaire to the general practitioner. Results: The mean duration of follow-up was 11.5 years. Survival at 5, 10, 15, and 20 years was 92%, 81%, 63%, and 53%, respectively, which is significantly lower than the expected survival (94%, 86%, 78%, and 66%, respectively). Survival was worse with higher age (P < .001). Survival among patients younger than 45 years and older than 65 years was comparable to the expected survival but significantly worse among patients aged 45-65 years. Analysis of the cause of death suggests an excess mortality associated with both brain tumor death and stroke (P = .07). Recurrence rates at 5, 10, and 15 years were 18%, 26%, and 32%, respectively. Higher Simpson grade (P < .001) and lower age (P = .02) were associated with a higher recurrence rate. In 29 patients (14%) receiving radiotherapy, the 5-year recurrence rate was 18% and the 5-year survival was only 58%. Long-term functioning (≥ 5 years after last treatment) could be assessed in 89 long-term survivors: 29 patients (33%) showed no deficits, and 60 (67%) showed at least 1 neurological symptom, of whom 24 (27%) were unable to perform normal daily activities. Conclusion: Long-term survival in WHO grade I meningioma is challenged in patients more than 45 years of age. Excess mortality seems to be associated with both tumor recurrence and stroke. The majority of patients have long-term neurological problems.

Neuro-oncology · 165 citationsread the source →

Telephone-delivered Acceptance and Commitment Therapy for adult smoking cessation: a feasibility study.

Background: Quitline smoking cessation counseling results in a mere 12% success rate. Testing of new telephone-delivered cessation counseling approaches is needed. Objective: Determine the feasibility of the first telephone-delivered Acceptance and Commitment Therapy (ACT) intervention for smoking cessation. Design: Fourteen adults (57% racial/ethnic minority, 8/14) in a single-arm study. Counselor proactively delivered a 5-session (90-min total) ACT telephone intervention for smoking cessation. Hypothesized ACT processes were self-reported at baseline and posttreatment. Smoking status was self-reported at baseline, 20-day posttreatment (93% retention, 13/14), and 12-month posttreatment (93% retention, 13/14). Results: (a) Delivery length and duration: average of 3.5 calls and 81.9-min intervention duration. (b) Receptivity: 100% (14/14) felt respected by the counselor, 86% (12/14) said that intervention was a good fit, and 93% (13/14) said that intervention helped them quit. (c) ACT processes: (i) acceptance of physical cravings, emotions, and thoughts that cue smoking increased from baseline to posttreatment (p = .001, p = .038, and p = .085, respectively) and (ii) commitment to quitting increased from baseline to posttreatment (p = .01). (4) Intent-to-treat cessation outcomes: (i) at 20-day posttreatment, 43% (6/14) had not smoked the day of the survey and 29% (4/14) had not smoked in past 7 days and (ii) at 12-month posttreatment, 29% (4/14) had not smoked at all in past 12 months. These quit rates are over double the 12% quit rates of current standard telephone counseling. Conclusion: Telephone-delivered ACT shows promise for smoking cessation and warrants future testing in a well-powered randomized trial.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 47 citationsread the source →

Problematic Internet use: an overview

The “global village”, a metaphor used to describe how the Internet has shortened distances and facilitated the flow of information, has grown to over one billion users 1. Statistics from across the world highlight its reach and penetrance: 90% of South Korean households connect to high-speed, inexpensive broadband 2; Londoners spend an average of 45 days a year online, more than they spend watching TV 3; and the rate of increase in the number of Internet users in Africa and the Middle East exceeded 1,300% between 2000 and 2009 4. For the majority of Internet users, the World Wide Web represents a tremendous wellspring of opportunity that enhances well-being. For others, however, it can lead to a state that appears to meet the DSM definition of a mental disorder, described as a “clinically significant behavioral or psychological syndrome…that is associated with present distress… or with a significantly increased risk of suffering death, pain, disability, or an important loss of freedom” 5. Scientific understanding of that state has lagged behind media attention 6, in part because of inconsistency in defining the problem 7, disagreement about its very existence 8, and the variable research methodology used in studying it. Still, a body of data by scientists from the East and West (with the East increasingly leading the way) tells a cautionary tale about the Internet's potential to bring about psychological harm. In 1996, the psychologist K. Young became the first to publish a detailed case report of problematic Internet use 9. Her “patient zero” was a non-technologically oriented 43-year-old homemaker with a “content home life and no prior addiction or psychiatric history”, who, within three months of discovering chat rooms, was spending up to 60 hours per week online. She reported feeling excited in front of the computer, and depressed, anxious, and irritable when she would log off. She described having an addiction to the medium “like one would to alcohol”. Within one year of purchasing her home computer, she was ignoring household chores, had quit social activities she used to enjoy, and had become estranged from her two teenage daughters and her husband of 17 years. Based on this and other patients she interviewed, Young proposed the first set of diagnostic criteria for what she termed “Internet addiction”. She modeled them on the DSM-IV definition for substance dependence because of similarities she observed with the states of tolerance (needing more of the substance to achieve the same effect) and withdrawal (psychological and physical discomfort upon reducing or stopping the substance) 9. Others conceptualized problematic Internet use as a behavioral addiction not involving an intoxicant 10, and Young subsequently updated her definition, adapting the DSM-IV criteria for pathological gambling, an impulse control disorder often described as a behavioral addiction, into her Diagnostic Questionnaire 11 (Table 1). The questionnaire, which required at least five of the eight criteria be met for the Internet addiction diagnosis, has not received adequate psychometric testing. Shapira et al 12 proposed five years later a more inclusive diagnostic schema in the general style of the impulse control disorders. They argued that definitions based solely on substance dependence or pathological gambling were too narrow to capture the population of problematic Internet users and could lead to premature conclusions about the new disorder and the patients. They eschewed the “Internet addiction” label for lack of scientific proof for true addiction and favored the less controversial “problematic Internet use”, defining it as: a) maladaptive preoccupation with Internet use, experienced as irresistible use for periods of time longer than intended; b) significant distress or impairment resulting from the behavior; and c) the absence of other Axis I pathology that might explain the behavior, such as mania or hypomania. To date, only two studies have attempted to develop diagnostic criteria empirically by testing them against the diagnosis made on the basis of a systematic psychiatric interview. Ko et al 13 tested a set of criteria in 468 Taiwanese high school students. Starting with 13 candidate criteria, they eliminated those with low diagnostic accuracy, and determined that a cutoff of six out of the nine remaining criteria had the best diagnostic accuracy while maintaining high specificity (97.1%) and acceptable sensitivity (87.5%). The criterion for functional impairment was listed separately as criterion B and was required for the diagnosis (Table 2). In a second study, Ko et al 14 confirmed the diagnostic accuracy of their criteria in an older cohort of 216 Taiwanese college students. However, the relatively small size of both studies and the non-representative nature of the groups studied limit the applicability of the proposed criteria to the general population. Several assessment scales have been proposed to screen for, and help diagnose, problematic Internet use. As a group, these instruments show no consensus on the underlying dimensions that constitute the condition 6,15. In addition to Young's Diagnostic Questionnaire, two are in relatively common use in research and/or clinical settings: Young's Internet Addiction Test 16 and the Chen Internet Addiction Scale 17. Young's Internet Addiction Test 16 consists of 20 “how-often” questions, each rated on a scale of 1 to 5 (1=rarely; 2=occasionally; 3=frequently; 4=often; 5=always.) A score of 80 or above is consistent with problematic use (Table 3). The psychometric properties of the instrument were studied in 86 subjects 18. Six factors were extracted from the questionnaire: salience, excessive use, neglect of work, anticipation, lack of control, and neglect of social life. These factors showed good concurrent validity and internal consistency. Salience explained most of the variance and was also found to be the most reliable as indicated by its Cronbach's alpha. However, the selection bias introduced by online recruitment and the small size of the study limit its value. The Chen Internet Addiction Scale 17 is a self-report instrument composed of 26 items rated on a 4-point Likert scale (adapted in Table 4). It assesses five domains of Internet-related problems: compulsive use, withdrawal, tolerance, interpersonal and health consequences, and time management difficulties. Scores range from 26 to 104. In a study of 454 Taiwanese adolescents who completed the scale and received a structured diagnostic interview, a cutoff of 64 was shown to have high diagnostic accuracy and specificity (88% and 92.6%, respectively) 19. The internal reliability of the scale and subscales in the original study ranged from 0.79 to 0.93 17. Due to the lack of consensus on diagnostic criteria and the dearth of large epidemiological studies, the prevalence of problematic Internet use in the general population has not been established. Overall, prevalence surveys conducted in various countries fall into two main categories, online vs. offline studies, with the former typically yielding higher rates, most likely because of inherent selection bias 20. Only two epidemiological studies exploring the prevalence of problematic Internet use in the general population have been published. One was conducted in the US, the other in Norway 20,21. The US study used random-digit telephone dialing (cellular phone numbers were not included) to interview 2,513 adults taken from all 50 states in a manner proportional to the population in each state 20. More than half of the people reached agreed to be interviewed. Participants’ average age was 48, and 51% fell in the middle class socioeconomic stratum. 68.9% were regular Internet users. The authors’ diagnostic definition, based on published criteria and on similarities with impulse control disorders, substance dependence and obsessive-compulsive disorder, required: a) Internet use that interferes in personal relationships; b) preoccupation with the Internet when offline; c) unsuccessful attempts at quitting or cutting down; and d) staying online longer than intended. This definition yielded a point prevalence of 0.7%. Less stringent definitions yielded higher prevalence rates, and individual features consistent with problematic Internet use were endorsed by as many as 13.7% (respondents who found it hard to stay offline for days in a row). In the second study, Bakken et al 21 mailed Young's Diagnostic Questionnaire to 10,000 inhabitants of Norway, randomly selected from a database of the entire population. 3,399 completed questionnaires were returned (a somewhat lower response rate than the US study). Recipients of the mailed questionnaire also had the option of completing it online. Among respondents, 87% were Internet users. The prevalence of “addicted Internet use” (≥5 questions answered “yes”) was calculated to be 1%, whereas the prevalence of “at risk” Internet use (3–4 questions answered “yes”) was 5.2%. Multivariate analysis showed young age, male gender, higher educational achievement, and financial stress to be positively associated with “problematic Internet use” (defined by the authors to include both “Internet addicts” and “at risk” respondents). Prevalence rates among adolescents have been researched more extensively, perhaps because the so-called “digital natives” grew up incorporating the Internet in many aspects of life and as a result are perceived to be at higher risk. However, even when online-based surveys are excluded, the results can vary widely and are difficult to compare, due to differences in Internet access, recruitment methodology, the exact age bracket studied, and the definitions utilized. Considering only relatively large and offline studies, research from China 22, South Korea 23,24, Greece 25, Norway 26, and Iran 27 has yielded prevalence estimates ranging between 2% and 11%. Problematic Internet use has not been incorporated into large-scale epidemiological studies aimed at estimating the relative prevalence of mental disorders. Still, a review of published studies reveals that the presence of other psychiatric conditions in patients with problematic Internet use is the rule rather than the exception 6. The studies, however, were not designed or statistically powered to detect the nature of the association (cause, effect, or independent). In Bakken's general-population study 21, based on subjects’ self-report, 41.4% of Internet “addicts” reported feelings of depression in the 12-month period prior to the study, compared to 15.8% of non-problematic users. Sleep disturbances, anxious feelings, and alcohol and substance abuse were also more common (38.6% vs. 26.4%, 36.4% vs. 5%, and 13.6% vs. 1.1%, respectively). However, the questions used to assess co-occurring psychological impairment were not based on established criteria for mood, sleep, anxiety, or substance use disorders. Two US case series involved face-to-face interviews of adult patients with problematic Internet use. Black et al 28 assessed 21 subjects with the Diagnostic Interview Schedule and found the lifetime prevalence of mood disorders and major depression to be 33% and 15%, respectively. Further, 38% had a lifetime substance use disorder and 19% had a lifetime diagnosis of anxiety disorder. In a case series that included 20 patients, Shapira et al 29 found a very high (70%) lifetime prevalence for bipolar affective disorder, type I or II, compared with 15% for major depression. Fifty-five percent had a lifetime prevalence of substance abuse, and 45% met criteria for social anxiety disorder. Fifty percent of subjects had a lifetime diagnosis of an impulse control disorder. The authors highlight their observation that patients’ Internet-related symptoms were more impulsive and egosyntonic than compulsive and egodystonic, concluding that problematic Internet use resembles the DSM-IV definition of an impulse control disorder more closely than that of obsessive-compulsive disorder. Our clinical experience supports this conclusion. As a group, surveys conducted among high school and college students show similarly high comorbidity rates with mood and anxiety disorders, but a link between attention-deficit/hyperactivity disorder (ADHD) and problematic Internet use seems more obvious than among adults. One study in 752 South Korean elementary students found that 33% of those with ADHD also met criteria for problematic Internet use 30. Another study in 216 Taiwanese college students showed that 32% subjects with problematic Internet use also had ADHD compared to only 8% of regular Internet users 31. Whether Web-based activities appeal to the short attention span of ADHD sufferers or whether excessive Internet use may cause inattention remains to be elucidated. The clinical evaluation of the patient with problematic Internet use should include a careful assessment of the comorbid conditions frequently present. Those should then be treated according to established treatment guidelines. To the extent that the Internet-related problem may stem from another diagnosis (e.g., a patient with severe social anxiety who starts leading a “virtual” life at the expense of offline interactions), it might improve as the primary condition is addressed. Pharmacotherapeutic and psychotherapeutic interventions specific to problematic Internet use have not yet received adequate testing in large, rigorous studies. Pharmacotherapy often begins with selective serotonin reuptake inhibitors (SSRIs). However, while effective in treating obsessive-compulsive disorder, SSRIs have shown mixed results in impulse control disorders 32,33,34,35–36. In light of the greater similarity between problematic Internet use and impulse control disorders compared to obsessive-compulsive disorder 29, it is unclear whether SSRIs will ultimately prove beneficial, and no double-blind placebo-controlled studies have been published so far. One discontinuation study tested escitalopram, 20 mg/day, in 19 subjects with problematic Internet use 37. During the 10-week open-label phase, subjects showed significant decreases in weekly hours spent online (from a mean of 36.8 hours to 16.5 hours) and improvement in global functioning. At the end of the 10 weeks, subjects were blindly randomized to either continued escitalopram treatment or to placebo. Beyond that, they were followed for 9 weeks. No significant difference was seen between the two groups at the end of the second phase, as gains achieved at week 10 were maintained in both treatment groups. The authors speculate that nine weeks may have not been sufficient for the effect to be lost in the placebo group or for additional gains to be made in the escitalopram group, but do not rule out the possibility that the improvement seen in the open-label phase may have been a placebo response. One case study reported successful treatment with naltrexone 38, a drug that has shown benefit in other impulse control disorders 39,40. The patient was a 31 year old male with compulsive cybersexual behavior who had failed antidepressants, group and individual psychotherapy, Sexual Addicts Anonymous, and pastoral counseling. Naltrexone (150 mg/day), gradually added to a stable dose of sertraline which on its own had been ineffective in treating his problematic Internet use, helped induce a three-year remission. The authors hypothesize that, by blocking the capacity of endogenous opioids to trigger dopamine release in response to reward, naltrexone may block the reinforcing nature of compulsive Internet sexual activity. Another case study reported the successful use of an atypical antipsychotic, quetiapine, 200 mg/day, gradually added to citalopram, in a 23 year old subject with problematic Internet use 41. The improvement was maintained at four-month follow-up. More recently, a study tested methylphenidate in 62 children with ADHD who were Internet video game players 42. Participants’ average age was around 9. After 8 weeks of treatment (average dose 30.5 mg/day), Internet usage decreased significantly and correlated with reduction in ADHD symptoms. The authors cautiously suggest that methylphenidate might be beneficial as a treatment for problematic Internet use, especially when co-occurring with ADHD. Of the psychotherapy approaches used, cognitive behavioral therapy (CBT) has received the most empiric investigation. The largest study enrolled 114 adult subjects and employed CBT interventions including: keeping a daily log of Internet activity, teaching time management skills, and confronting cognitive distortions and rationalizations frequently used by patients to justify continued Internet usage, such as “just a few more minutes won't hurt” 43. Most subjects were able to control their symptoms by the eighth session, and improvement was sustained over a 6-month follow-up. For children and adolescents, family-based interventions that improve communication and teach family monitoring of Internet use can be helpful 44. However, the intensive (and typically very expensive) residential treatment options that have received much media attention have undergone little empiric investigation to warrant a strong recommendation 2,45. The same applies to online treatment websites that encourage the person with problematic Internet use to “click here if you are addicted to the Internet”. For a medium that has so radically changed the way we conduct our lives, the Internet's effects on our psychological health remain understudied. Simply stating that similar fears were raised when the radio, movies and early video games were introduced is not sufficient: the immersive and interactive qualities of the virtual world, and its sheer penetrance, make it potentially more serious. Also deserving of exploration are the more subtle psychological changes that occur in the virtual world, such as online disinhibition and increased risk-taking 46. Those changes are not necessarily evidence of “Internet addiction”, and may not be pathological, but, as important features of the new virtual psychology, should also be studied. As our field continues to debate whether their condition belongs in the next edition of the DSM 47, patients continue to present with symptoms born out of the digital age, and their symptoms are changing as the technology evolves from browsers, to “crackberries”, to “smart phones” that combine texting, talking, video games, and browsing in one device that to many is like a new appendage. Even the “problematic Internet use” designation now seems outdated, which is why some have wisely opted for “pathological use of electronic media”, instead 47. Technology, like media outlets, remains far ahead of scientific investigation. Given the dramatic changes that our society is undergoing as a result of the Internet revolution, it behooves us to try to bridge the gap.

World Psychiatry · 340 citationsread the source →

Careful selection and close monitoring of low-risk prostate cancer patients on active surveillance minimizes the need for treatment.

Background: With the advent of prostate-specific antigen (PSA) screening and the increase in the number of transrectal ultrasound-guided biopsy cores, there has been a dramatic rise in the incidence of low-risk prostate cancer (LRPC). Because > 97% of men with LRPC are likely to die of something other than prostate cancer, it is critical that patients give thought to whether early curative treatment is the only option at diagnosis. Objective: To identify a group of men with LRPC who may not require initial treatment and monitor them on our active surveillance (AS) protocol, to determine the percentage treated and the outcome and to analyze the quality-of-life data. Design, setting, and participants: We defined patients eligible for AS as Gleason ≤ 6, PSA ≤ 10, and two or fewer biopsy cores with ≤ 20% tumor in each core. Measurements: Kaplan Meier analysis was used to predict the 5-year treatment free survival. Logistic regression determined the predictors of treatment. Data on sexual function, continence, and outcome were obtained and analyzed. Results and limitations: The AS cohort consisted of 230 patients with a mean age of 63.4 yr; 86% remained on AS for a mean follow-up of 44 mo. Thirty-two of the 230 patients (14%) were treated for a mean follow-up of 33 mo. Twelve had a total prostatectomy (TP). The pathologic stage of these patients was similar to initially treated TP patients with LRPC. Fourteen underwent radiation therapy, and six underwent androgen-deprivation therapy. Fifty percent of patients had no tumor on the first rebiopsy, and only 5% of these patients were subsequently treated. PSA doubling time and clinical stage were not predictors of treatment. No patient progressed after treatment. Among the AS patients, 30% had incontinence, yet < 15% were bothered by it. As measured by the Sexual Health Inventory for Men, 49% of patients had, at a minimum, moderate (≤ 16) erectile dysfunction. Conclusions: If guidelines for AS are narrowly defined to include only patients with Gleason 6, tumor volume ≤ 20% in one or two biopsy cores, and PSA levels ≤ 10, few patients are likely to require treatment. Progression-free survival of those treated is likely to be equivalent to patients with similar clinical findings treated at diagnosis.

European urology · 190 citationsread the source →