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Efficacy of functional remediation in bipolar disorder: a multicenter randomized controlled study.

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukey's post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

The American journal of psychiatry · randomised controlled trial · 211 citationsread the source →

Prevalence, Risk Factors, and Correlates of Anxiety at 1 Year After Moderate to Severe Traumatic Brain Injury.

Objective: To determine at 1 year after moderate to severe traumatic brain injury the (1) rate of clinically significant anxiety; (2) rates of specific symptoms of anxiety; (3) risk factors for anxiety; and (4) associations of anxiety with other 1-year outcomes, including participation and quality of life. Design: Prospective longitudinal observational study. Setting: Inpatient rehabilitation centers, with data capture at injury and 1-year follow-up. Participants: Persons with moderate to severe traumatic brain injury who were enrolled in the Traumatic Brain Injury Model Systems database (N=1838). Interventions: Not applicable. Main outcome measures: The 7-item Generalized Anxiety Disorder Scale, Patient Health Questionnaire (9-item screen for depression), FIM, Participation Assessment with Recombined Tools-Objective, and Satisfaction with Life Scale. Results: Clinically significant anxiety was reported by 21% of the participants. Of these, >80% reported interference with daily activities, with the most common symptoms being excessive worry and irritability. A common pattern was comorbid anxiety and depression, with smaller proportions reporting either disorder alone. Anxiety had large effect sizes with respect to life satisfaction and cognitive disability and medium to small effect sizes relative to societal participation and self-care. Middle age, black race, lower socioeconomic status, preinjury mental health treatment, and at least 1 traumatic brain injury prior to the index injury were all risk factors for later anxiety. Conclusions: Anxiety should be screened, fully evaluated, and treated after moderate to severe traumatic brain injury. Worry and irritability might be treated with pharmacologic agents or relatively simple behavioral interventions, which should be further researched in this population.

Archives of physical medicine and rehabilitation · cohort or longitudinal · 41 citationsread the source →

Effect of Computer-Assisted Cognitive Behavior Therapy vs Usual Care on Depression Among Adults in Primary Care: A Randomized Clinical Trial.

Importance: Depression is a common disorder that may go untreated or receive suboptimal care in primary care settings. Computer-assisted cognitive behavior therapy (CCBT) has been proposed as a method for improving access to effective psychotherapy, reducing cost, and increasing the convenience and efficiency of treatment for depression. Objectives: To evaluate whether clinician-supported CCBT is more effective than treatment as usual (TAU) in primary care patients with depression and to examine the feasibility and implementation of CCBT in a primary care population with substantial numbers of patients with low income, limited internet access, and low levels of educational attainment. Design, setting, and participants: This randomized clinical trial included adult primary care patients from clinical practices at the University of Louisville who scored 10 or greater on the Patient Health Questionnaire-9 (PHQ-9) and were randomly assigned to CCBT or TAU for 12 weeks of active treatment. Follow-up assessments were conducted 3 and 6 months after treatment completion. Enrollment occurred from June 24, 2016, to May 13, 2019. The last follow-up assessment was conducted on January 30, 2020. Interventions: CCBT included use of the 9-lesson computer program Good Days Ahead, along with as many as 12 weekly telephonic support sessions of approximately 20 minutes with a master's level therapist, in addition to TAU, which consisted of the standard clinical management procedures at the primary care sites. TAU was uncontrolled, but use of antidepressants and psychotherapy other than CCBT was recorded. Main outcomes and measures: The primary outcome measure (PHQ-9) and secondary outcome measures (Automatic Thoughts Questionnaire for negative cognitions, Generalized Anxiety Disorder-7, and the Satisfaction with Life Scale for quality of life) were administered at baseline, 12 weeks, and 3 and 6 months after treatment completion. Satisfaction with treatment was assessed with the Client Satisfaction Questionnaire-8. Results: The sample of 175 patients was predominately female (147 of 174 [84.5%]) and had a high proportion of individuals who identified as racial and ethnic minority groups (African American, 44 of 162 patients who reported [27.2%]; American Indian or Alaska Native, 2 [1.2%]; Hispanic, 4 [2.5%]; multiracial, 14 [8.6%]). An annual income of less than $30 000 was reported by 88 of 143 patients (61.5%). Overall, 95 patients (54.3%) were randomly assigned to CCBT and 80 (45.7%) to TAU. Dropout rates were 22.1% for CCBT (21 patients) and 30.0% for TAU (24 patients). An intent-to-treat analysis found that CCBT led to significantly greater improvement in PHQ-9 scores than TAU at posttreatment (mean difference, -2.5; 95% CI, -4.5 to -0.8; P = .005) and 3 month (mean difference, -2.3; 95% CI, -4.5 to -0.8; P = .006) and 6 month (mean difference, -3.2; 95% CI, -4.5 to -0.8; P = .007) follow-up points. Posttreatment response and remission rates were also significantly higher for CCBT (response, 58.4% [95% CI, 46.4-70.4%]; remission, 27.3% [95% CI, 16.4%-38.2%]) than TAU (response, 33.1% [95% CI, 20.7%-45.5%]; remission, 12.0% [95% CI, 3.3%- 20.7%]). Conclusions and relevance: In this randomized clinical trial, CCBT was found to have significantly greater effects on depressive symptoms than TAU in primary care patients with depression. Because the study population included people with lower income and lack of internet access who typically have been underrepresented or not included in earlier investigations of CCBT, results suggest that this form of treatment can be acceptable and useful in diverse primary care settings. Additional studies with larger samples are needed to address implementation procedures that could enhance the effectiveness of CCBT and to examine potential factors associated with treatment outcome. Trial registration: ClinicalTrials.gov Identifier: NCT02700009.

JAMA network open · randomised controlled trial · 23 citationsread the source →

Impact of COVID-19 on household food insecurity and interlinkages with child feeding practices and coping strategies in Uttar Pradesh, India: a longitudinal community-based study.

Objectives: The COVID-19 pandemic has profound negative impacts on people's lives, but little is known on its effect on household food insecurity (HFI) in poor setting resources. This study assessed changes in HFI during the pandemic and examined the interlinkages between HFI with child feeding practices and coping strategies. Design: A longitudinal survey in December 2019 (in-person) and August 2020 (by phone). Setting: Community-based individuals from 26 blocks in 2 districts in Uttar Pradesh, India. Participants: Mothers with children <2 years (n=569). Main outcomes and analyses: We measured HFI by using the HFI Access Scale and examined the changes in HFI during the pandemic using the Wilcoxon matched-pairs signed-rank tests. We then assessed child feeding practices and coping strategies by HFI status using multivariable regression models. Results: HFI increased sharply from 21% in December 2019 to 80% in August 2020, with 62% households changing the status from food secure to insecure over this period. Children in newly or consistently food-insecure households were less likely to consume a diverse diet (adjusted OR, AOR 0.57, 95% CI 0.34 to 0.95 and AOR 0.51, 95% CI 0.23 to 1.12, respectively) compared with those in food-secure households. Households with consistent food insecurity were more likely to engage in coping strategies such as reducing other essential non-food expenditures (AOR 2.2, 95% CI 1.09 to 4.24), borrowing money to buy food (AOR 4.3, 95% CI 2.31 to 7.95) or selling jewellery (AOR 5.0, 95% CI 1.74 to 14.27) to obtain foods. Similar findings were observed for newly food-insecure households. Conclusions: The COVID-19 pandemic and its lockdown measures posed a significant risk to HFI which in turn had implications for child feeding practices and coping strategies. Our findings highlight the need for further investment in targeted social protection strategies and safety nets as part of multisectoral solutions to improve HFI during and after COVID-19.

BMJ open · 41 citationsread the source →

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

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

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

A one year trial of methylphenidate in the treatment of ADHD.

Objective: To determine the effects of long-term methylphenidate treatment on symptom severity and social adjustment in adult ADHD. Method: Adults (n = 116) meeting operational diagnostic criteria for ADHD (the "Utah Criteria") entered a randomized double-blind crossover trial of methylphenidate and placebo. Participants who improved on immediate-release methylphenidate entered a 12-month, open-label trial. Outcomes were assessed using the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), Clinical Global Impression-Improvement (CGI-I), global assessment of functioning (GAF), and the Weissman Social Adjustment Scale (WSAS). Results: In the double-blind trial more patients improved (50% reduction of symptoms) receiving methylphenidate (74%) than placebo (21%, p = .001). During the open-label trial, symptom severity decreased 80% from baseline, and the WSAS decreased >50% in all subscales. The average GAF improved significantly (p < .0001). Conclusion: ADHD adults, who responded to methylphenidate in a short-tem, placebo-controlled trial, responded to long-term treatment with marked improvements in ADHD symptoms and psychosocial functioning.

Journal of attention disorders · randomised controlled trial · 47 citationsread the source →

Recruiting and retaining young adults: what can we learn from behavioural interventions targeting nutrition, physical activity and/or obesity? A systematic review of the literature.

Objective: To describe strategies used to recruit and retain young adults in nutrition, physical activity and/or obesity intervention studies, and quantify the success and efficiency of these strategies. Design: A systematic review was conducted. The search included six electronic databases to identify randomised controlled trials (RCT) published up to 6 December 2019 that evaluated nutrition, physical activity and/or obesity interventions in young adults (17-35 years). Recruitment was considered successful if the pre-determined sample size goal was met. Retention was considered acceptable if ≥80 % retained for ≤6-month follow-up or ≥70 % for >6-month follow-up. Results: From 21 582 manuscripts identified, 107 RCT were included. Universities were the most common recruitment setting used in eighty-four studies (79 %). Less than half (46 %) of the studies provided sufficient information to evaluate whether individual recruitment strategies met sample size goals, with 77 % successfully achieving recruitment targets. Reporting for retention was slightly better with 69 % of studies providing sufficient information to determine whether individual retention strategies achieved adequate retention rates. Of these, 65 % had adequate retention. Conclusions: This review highlights poor reporting of recruitment and retention information across trials. Findings may not be applicable outside a university setting. Guidance on how to improve reporting practices to optimise recruitment and retention strategies within young adults could assist researchers in improving outcomes.

Public health nutrition · systematic review · 35 citationsread the source →

Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis.

Background: Several interventions are available for management of obsessive-compulsive disorder in adults, but few studies have compared their relative efficacy in a single analysis. We aimed to simultaneously compare all available treatments using both direct and indirect data. Methods: In this systematic review and network meta-analysis, we searched the two controlled trials registers maintained by the Cochrane Collaboration Common Mental Disorders group for trials published up to Feb 16, 2016. We selected randomised controlled trials in which an active psychotherapeutic or pharmacological intervention had been used in adults with obsessive-compulsive disorder. We allowed all comorbidities except for schizophrenia or bipolar disorder. We excluded studies that focused exclusively on treatment-resistant patient populations defined within the same study. We extracted data from published reports. The primary outcome was symptom severity as measured by the Yale-Brown Obsessive Compulsive Scale. We report mean differences with 95% credible intervals compared with placebo. This study is registered with PROSPERO, number CRD42012002441. Findings: We identified 1480 articles in our search and included 53 articles (54 trials; 6652 participants) in the network meta-analysis. Behavioural therapy (mean difference -14·48 [95% credible interval -18·61 to -10·23]; 11 trials and 287 patients), cognitive therapy (-13·36 [-18·40 to -8·21]; six trials and 172 patients), behavioural therapy and clomipramine (-12·97 [-19·18 to -6·74]; one trial and 31 patients), cognitive behavioural therapy and fluvoxamine (-7·50 [-13·89 to -1·17]; one trial and six patients), cognitive behavioural therapy (-5·37 [-9·10 to -1·63]; nine trials and 231 patients), clomipramine (-4·72 [-6·85 to -2·60]; 13 trials and 831 patients), and all SSRIs (class effect -3·49 [95% credible interval -5·12 to -1·81]; 37 trials and 3158 patients) had greater effects than did drug placebo. Clomipramine was not better than were SSRIs (-1·23 [-3·41 to 0·94]). Psychotherapeutic interventions had a greater effect than did medications, but a serious limitation was that most psychotherapeutic trials included patients who were taking stable doses of antidepressants (12 [80%] of the 15 psychotherapy trials explicitly allowed antidepressants). Interpretation: A range of interventions is effective in the management of obsessive-compulsive disorder, but considerable uncertainty and limitations exist regarding their relative efficacy. Taking all the evidence into account, the combination of psychotherapeutic and psychopharmacological interventions is likely to be more effective than are psychotherapeutic interventions alone, at least in severe obsessive-compulsive disorder. Funding: National Institute for Health Research.

The lancet. Psychiatry · systematic review · 236 citationsread the source →

Primary Care Interventions to Support Breastfeeding: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Although 80% of infants in the United States start breastfeeding, only 22% are exclusively breastfed up to around 6 months as recommended by a number of professional organizations. Objective: To systematically review the evidence on the benefits and harms of breastfeeding interventions to support the US Preventive Services Task Force in updating its 2008 recommendation. Data sources: MEDLINE, PubMed, Cumulative Index for Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and PsycINFO for studies published in the English language between January 1, 2008, and September 25, 2015. Studies included in the previous review were re-evaluated for inclusion. Surveillance for new evidence in targeted publications was conducted through January 26, 2016. Study selection: Review of randomized clinical trials and before-and-after studies with concurrent controls conducted in a developed country that evaluated a primary care-relevant breastfeeding intervention among mothers of full- or near-term infants. Of 211 full-text articles reviewed, 52 studies met inclusion criteria. Thirty-one studies were newly identified, and 21 studies were carried forward from the previous review. Data extraction and synthesis: Independent critical appraisal of all provisionally included studies. Data were independently abstracted by one reviewer and confirmed by another. Main outcomes and measures: Child and maternal health outcomes, rates and duration of breastfeeding, and harms related to interventions as prespecified before data collection. Results: Fifty-two studies (n = 66 757) in 57 publications were included. Six trials (n = 2219) reported inconsistent effects of the interventions on infant health outcomes; no studies reported maternal health outcomes. Pooled estimates based on random-effects meta-analyses using the DerSimonian and Laird method indicated beneficial associations between individual-level breastfeeding interventions and any breastfeeding for less than 3 months (risk ratio [RR], 1.07 [95% CI, 1.03-1.11]; 26 studies [n = 11 588]), at 3 to less than 6 months (RR, 1.11 [95% CI, 1.04-1.18]; 23 studies [n = 8942]), and for exclusive breastfeeding for less than 3 months (RR, 1.21 [95% CI, 1.11-1.33]; 22 studies [n = 8246]), 3 to less than 6 months (RR, 1.20 [95% CI, 1.05-1.38]; 18 studies [n = 7027]), and at 6 months (RR, 1.16 [95% CI, 1.02-1.32]; 17 studies [n = 7690]). Absolute differences in the rates of any breastfeeding ranged from 14.1% in favor of the control group to 18.4% in favor of the intervention group. There was no significant association between interventions and breastfeeding initiation (RR, 1.00 [95% CI, 0.99-1.02]; 14 studies [n = 9428]). There was limited mixed evidence of an association between system-level interventions and rates of breastfeeding from well-controlled studies as well as for harms related to breastfeeding interventions, including maternal anxiety scores, decreased confidence, and concerns about confidentiality. Conclusions and relevance: The updated evidence confirms that breastfeeding support interventions are associated with an increase in the rates of any and exclusive breastfeeding. There are limited well-controlled studies examining the effectiveness of system-level policies and practices on rates of breastfeeding or child health and none for maternal health.

JAMA · systematic review · 105 citationsread the source →

Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.

Background: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder. Methods: We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291. Findings: We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low. Interpretation: All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants. Funding: National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.

Lancet (London, England) · systematic review · 2220 citationsread the source →

Burn size determines the inflammatory and hypermetabolic response.

Background: Increased burn size leads to increased mortality of burned patients. Whether mortality is due to inflammation, hypermetabolism or other pathophysiologic contributing factors is not entirely determined. The purpose of the present study was to determine in a large prospective clinical trial whether different burn sizes are associated with differences in inflammation, body composition, protein synthesis, or organ function. Methods: Pediatric burned patients were divided into four burn size groups: <40% total body surface area (TBSA) burn, 40-59% TBSA burn, 60-79% TBSA burn, and >80% TBSA burn. Demographic and clinical data, hypermetabolism, the inflammatory response, body composition, the muscle protein net balance, serum and urine hormones and proteins, and cardiac function and changes in liver size were determined. Results: One hundred and eighty-nine pediatric patients of similar age and gender distribution were included in the study (<40% TBSA burn, n = 43; 40-59% TBSA burn, n = 79; 60-79% TBSA burn, n = 46; >80% TBSA burn, n = 21). Patients with larger burns had more operations, a greater incidence of infections and sepsis, and higher mortality rates compared with the other groups (P < 0.05). The percentage predicted resting energy expenditure was highest in the >80% TBSA group, followed by the 60-79% TBSA burn group (P < 0.05). Children with >80% burns lost the most body weight, lean body mass, muscle protein and bone mineral content (P < 0.05). The urine cortisol concentration was highest in the 80-99% and 60-79% TBSA burn groups, associated with significant myocardial depression and increased change in liver size (P < 0.05). The cytokine profile showed distinct differences in expression of IL-8, TNF, IL-6, IL-12p70, monocyte chemoattractant protein-1 and granulocyte-macrophage colony-stimulating factor (P < 0.05). Conclusion: Morbidity and mortality in burned patients is burn size dependent, starts at a 60% TBSA burn and is due to an increased hypermetabolic and inflammatory reaction, along with impaired cardiac function.

Critical care (London, England) · 208 citationsread the source →

A task-shared, collaborative care psychosocial intervention for improving depressive symptomatology among older adults in a socioeconomically deprived area of Brazil (PROACTIVE): a pragmatic, two-arm, parallel-group, cluster-randomised controlled trial.

Background: There is an urgent need to reduce the burden of depression among older adults in low-income and middle-income countries (LMICs). We aimed to evaluate the efficacy of a task-shared, collaborative care psychosocial intervention for improving recovery from depression in older adults in Brazil. Methods: PROACTIVE was a pragmatic, two-arm, parallel-group, cluster-randomised controlled trial conducted in Guarulhos, Brazil. Primary care clinics (clusters) were stratified by educational level and randomly allocated (1:1) to either enhanced usual care alone (control group) or to enhanced usual care plus the psychosocial intervention (intervention group), which involved a 17-week psychosocial programme based on psychoeducation and behavioural activation approaches. Individuals approached for the initial screening assessment were selected randomly from a list of individuals provided by the Health Secretariat of Guarulhos. Face-to-face baseline assessments were conducted among adults aged 60 years or older registered with one of the primary care clinics and identified with clinically significant depressive symptomatology (9-item Patient Health Questionnaire [PHQ-9] score ≥10). Community health workers delivered the programme through home sessions, supported by a dedicated tablet application. Masking of clinic staff and community health workers who delivered the intervention was not feasible; however, research assistants conducting recruitment and follow-up assessments were masked to trial allocation. The primary outcome was recovery from depression (PHQ-9 score <10) at 8-month follow-up. All primary analyses were performed by intention to treat with imputed data. Adaptations to the protocol were made due to the COVID-19 pandemic; recruitment and intervention home sessions were stopped, and follow-up assessments were conducted by telephone. This trial is registered with the ISRCTN registry, ISRCTN57805470. Findings: We identified 24 primary care clinics in Guarulhos that were willing to participate, of which 20 were randomly allocated to either the control group (ten [50%] clusters) or to the intervention group (ten [50%] clusters). The four remaining eligible clusters were kept as reserves. Between May 23, 2019, and Feb 21, 2020, 8146 individuals were assessed for eligibility, of whom 715 (8·8%) participants were recruited: 355 (49·7%) in the control group and 360 (50·3%) in the intervention group. 284 (80·0%) participants in the control group and 253 (70·3%) in the intervention group completed follow-up at 8 months. At 8-month follow-up, 158 (62·5%) participants in the intervention group showed recovery from depression (PHQ-9 score <10) compared with 125 (44·0%) in the control group (adjusted odds ratio 2·16 [95% CI 1·47-3·18]; p<0·0001). These findings were maintained in the complete case analysis. No adverse events related to the intervention were observed. Interpretation: Although the COVID-19 pandemic altered delivery of the intervention, the low-intensity psychosocial intervention delivered mainly by non-mental health professionals was highly efficacious in improving recovery from depression in older adults in Brazil. Our results support a low-resource intervention that could be useful to reduce the treatment gap for depression among older people in other LMICs. Funding: São Paulo Research Foundation and Joint Global Health Trials (UK Department for International Development, Medical Research Council, and the Wellcome Trust).

The lancet. Healthy longevity · randomised controlled trial · 25 citationsread the source →

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

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

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

Evaluation of Drinking Risk Levels as Outcomes in Alcohol Pharmacotherapy Trials: A Secondary Analysis of 3 Randomized Clinical Trials.

Importance: The US Food and Drug Administration recognizes total abstinence and no heavy drinking days as outcomes for pivotal pharmacotherapy trials for alcohol use disorder (AUD). Many patients have difficulty achieving these outcomes, which can discourage seeking treatment and has slowed the development of medications that affect alcohol use. Objective: To compare 2 drinking-reduction outcomes with total abstinence and no heavy drinking outcomes. Design, setting, and participants: Data were obtained from 3 multisite, randomized, placebo-controlled clinical trials of medications for treating alcohol dependence (naltrexone, varenicline, and topiramate) in adults with DSM-IV-categorized alcohol dependence. Main outcomes and measures: Within each trial, the percentage of participants in active and placebo conditions who met responder definitions of abstinence, no heavy drinking days, a WHO 1-level reduction, and a WHO 2-level reduction was computed by month with corresponding effect sizes (Cohen h). Results: Across the 3 trials (N = 1169; mean [SD] age, 45 [10] years; 824 [70.5%] men), the percentage of participants classified as responders during the last 4 weeks of treatment was lowest for abstinence (naltrexone, 34.7% [100 of 288]; varenicline, 7.3% [7 of 96]; topiramate, 11.7% [21 of 179]) followed by no heavy drinking days (naltrexone, 51.0% [147 of 288]; varenicline, 24.0% [23 of 96]; topiramate, 20.7% [37 of 179]), WHO 2-level reduction (naltrexone, 75.0% [216 of 288]; varenicline, 55.2% [53 of 96]; topiramate, 44.7% [80 of 179]), and WHO 1-level reduction (naltrexone, 83.3% [240 of 288]; varenicline, 69.8 [67 of 96]; topiramate, 54.7% [98 of 179]) outcomes. Standardized treatment effects observed for the WHO 2-level reduction outcomes (naltrexone, Cohen h = 0.214 [95% CI, 0.053 -0.375]; varenicline, 0.273 [95% CI, -0.006 to 0.553]; topiramate, 0.230 [95% CI, 0.024-0.435]) and WHO 1-level reduction (naltrexone, Cohen h = 0.116 [95% CI, -0.046 to 0.277]; varenicline, 0.338 [95% CI, 0.058-0.617]; topiramate, 0.014 [95% CI, -0.192 to 0.219]) were comparable with those obtained using abstinence (naltrexone, Cohen h = 0.142 [95% CI, -0.020 to 0.303]; varenicline, 0.146 [95% CI, -0.133 to 0.426]; topiramate, 0.369 [95% CI, 0.163-0.574]) and no heavy drinking days (naltrexone, Cohen h = 0.140 [95% CI, -0.021 to 0.302]; varenicline, 0.232 [95% CI, -0.048 to 0.511]; topiramate, 0.207 [95% CI, 0.002-0.413]). Conclusions and relevance: WHO drinking risk level reductions appear to be worthwhile indicators of treatment outcome in AUD pharmacotherapy trials. These outcomes may align with drinking reduction goals of many patients and capture clinically meaningful improvements experienced by more patients than either abstinence or no heavy drinking days. Trial registration: ClinicalTrials.gov identifiers: NCT00006206; NCT01146613; NCT00210925.

JAMA psychiatry · randomised controlled trial · 98 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 →

CollAborative care for Screen-Positive EldeRs with major depression (CASPER plus): a multicentred randomised controlled trial of clinical effectiveness and cost-effectiveness.

Background: Depression in older adults is common and is associated with poor quality of life, increased morbidity and early mortality, and increased health and social care use. Collaborative care, a low-intensity intervention for depression that is shown to be effective in working-age adults, has not yet been evaluated in older people with depression who are managed in UK primary care. The CollAborative care for Screen-Positive EldeRs (CASPER) plus trial fills the evidence gap identified by the most recent guidelines on depression management. Objectives: To establish the clinical effectiveness and cost-effectiveness of collaborative care for older adults with major depressive disorder in primary care. Design: A pragmatic, multicentred, two-arm, parallel, individually randomised controlled trial with embedded qualitative study. Participants were automatically randomised by computer, by the York Trials Unit Randomisation Service, on a 1 : 1 basis using simple unstratified randomisation after informed consent and baseline measures were collected. Blinding was not possible. Setting: Sixty-nine general practices in the north of England. Participants: A total of 485 participants aged ≥ 65 years with major depressive disorder. Interventions: A low-intensity intervention of collaborative care, including behavioural activation, delivered by a case manager for an average of six sessions over 7-8 weeks, alongside usual general practitioner (GP) care. The control arm received only usual GP care. Main outcome measures: The primary outcome measure was Patient Health Questionnaire-9 items score at 4 months post randomisation. Secondary outcome measures included depression severity and caseness at 12 and 18 months, the EuroQol-5 Dimensions, Short Form questionnaire-12 items, Patient Health Questionnaire-15 items, Generalised Anxiety Disorder-7 items, Connor-Davidson Resilience Scale-2 items, a medication questionnaire, objective data and adverse events. Participants were followed up at 12 and 18 months. Results: In total, 485 participants were randomised (collaborative care, n = 249; usual care, n = 236), with 390 participants (80%: collaborative care, 75%; usual care, 86%) followed up at 4 months, 358 participants (74%: collaborative care, 70%; usual care, 78%) followed up at 12 months and 344 participants (71%: collaborative care, 67%; usual care, 75%) followed up at 18 months. A total of 415 participants were included in primary analysis (collaborative care, n = 198; usual care, n = 217), which revealed a statistically significant effect in favour of collaborative care at the primary end point at 4 months [8.98 vs. 10.90 score points, mean difference 1.92 score points, 95% confidence interval (CI) 0.85 to 2.99 score points; p  < 0.001], equivalent to a standard effect size of 0.34. However, treatment differences were not maintained in the longer term (at 12 months: 0.19 score points, 95% CI -0.92 to 1.29 score points; p = 0.741; at 18 months: < 0.01 score points, 95% CI -1.12 to 1.12 score points; p = 0.997). The study recorded details of all serious adverse events (SAEs), which consisted of 'unscheduled hospitalisation', 'other medically important condition' and 'death'. No SAEs were related to the intervention. Collaborative care showed a small but non-significant increase in quality-adjusted life-years (QALYs) over the 18-month period, with a higher cost. Overall, the mean cost per incremental QALY for collaborative care compared with usual care was £26,016; however, for participants attending six or more sessions, collaborative care appears to represent better value for money (£9876/QALY). Limitations: Study limitations are identified at different stages: design (blinding unfeasible, potential contamination), process (relatively low overall consent rate, differential attrition/retention rates) and analysis (no baseline health-care resource cost or secondary/social care data). Conclusion: Collaborative care was effective for older people with case-level depression across a range of outcomes in the short term though the reduction in depression severity was not maintained over the longer term of 12 or 18 months. Participants who received six or more sessions of collaborative care did benefit substantially more than those who received fewer treatment sessions but this difference was not statistically significant. Future work recommendations: Recommendations for future research include investigating the longer-term effect of the intervention. Depression is a recurrent disorder and it would be useful to assess its impact on relapse and the prevention of future case-level depression. Trial registration: Current Controlled Trials ISRCTN45842879. 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. 67. See the NIHR Journals Library website for further project information.

Health technology assessment (Winchester, England) · randomised controlled trial · 33 citationsread the source →

Psychosocial Effect of Newborn Genomic Sequencing on Families in the BabySeq Project: A Randomized Clinical Trial.

Importance: Newborn genomic sequencing (nGS) may provide health benefits throughout the life span, but there are concerns that it could also have an unfavorable (ie, negative) psychosocial effect on families. Objective: To assess the psychosocial effect of nGS on families from the BabySeq Project, a randomized clinical trial evaluating the effect of nGS on the clinical care of newborns from well-baby nurseries and intensive care units. Design, setting, and participants: In this randomized clinical trial conducted from May 14, 2015, to May 21, 2019, at well-baby nurseries and intensive care units at 3 Boston, Massachusetts, area hospitals, 519 parents of 325 infants completed surveys at enrollment, immediately after disclosure of nGS results, and 3 and 10 months after results disclosure. Statistical analysis was performed on a per-protocol basis from January 16, 2019, to December 1, 2019. Intervention: Newborns were randomized to receive either standard newborn screening and a family history report (control group) or the same plus an nGS report of childhood-onset conditions and highly actionable adult-onset conditions (nGS group). Main outcomes and measures: Mean responses were compared between groups and, within the nGS group, between parents of children who received a monogenic disease risk finding and those who did not in 3 domains of psychosocial impact: parent-child relationship (Mother-to-Infant Bonding Scale), parents' relationship (Kansas Marital Satisfaction Scale), and parents' psychological distress (Edinburgh Postnatal Depression Scale anxiety subscale). Results: A total of 519 parents (275 women [53.0%]; mean [SD] age, 35.1 [4.5] years) were included in this study. Although mean scores differed for some outcomes at singular time points, generalized estimating equations models did not show meaningful differences in parent-child relationship (between-group difference in adjusted mean [SE] Mother-to-Infant Bonding Scale scores: postdisclosure, 0.04 [0.15]; 3 months, -0.18 [0.18]; 10 months, -0.07 [0.20]; joint P = .57) or parents' psychological distress (between-group ratio of adjusted mean [SE] Edinburgh Postnatal Depression Scale anxiety subscale scores: postdisclosure, 1.04 [0.08]; 3 months, 1.07 [0.11]; joint P = .80) response patterns between study groups over time for any measures analyzed in these 2 domains. Response patterns on one parents' relationship measure differed between groups over time (between-group difference in adjusted mean [SE] Kansas Marital Satisfaction Scale scores: postdisclosure, -0.19 [0.07]; 3 months, -0.04 [0.07]; and 10 months, -0.01 [0.08]; joint P = .02), but the effect decreased over time and no difference was observed on the conflict measure responses over time. We found no evidence of persistent negative psychosocial effect in any domain. Conclusions and relevance: In this randomized clinical trial of nGS, there was no persistent negative psychosocial effect on families among those who received nGS nor among those who received a monogenic disease risk finding for their infant. Trial registration: ClinicalTrials.gov Identifier: NCT02422511.

JAMA pediatrics · randomised controlled trial · 70 citationsread the source →

An online healthy relationship tool and safety decision aid for women experiencing intimate partner violence (I-DECIDE): a randomised controlled trial.

Background: Evidence for online interventions to help women experiencing intimate partner violence is scarce. We assessed whether an online interactive healthy relationship tool and safety decision aid (I-DECIDE) would increase women's self-efficacy and improve depressive symptoms compared with an intimate partner violence information website. Methods: In this two-group pragmatic randomised controlled trial, we enrolled women who had screened positive for any form of intimate partner violence or fear of a partner in the 6 months before recruitment. Women aged 16-50 years currently residing in Australia, who had safe access to a computer and an internet connection, and who answered positively to one of the screening questions in English were eligible for inclusion. Participants were randomly assigned (1:1) by computer to receive either the intervention or control website. The intervention website consisted of modules on healthy relationships, abuse and safety, and relationship priority setting, and a tailored action plan. The control website was a static intimate partner violence information website. As the initial portion of the website containing the baseline questions was identical for both groups, there was no way for women to tell which group they had been allocated to, and the research team were also masked to participant allocation until after analysis of the 12-month data. Data were collected at baseline, immediately after completion of the website, at 6 months, and 12 months. Primary outcomes were mean general self-efficacy score (immediately after website completion, and at 6 months and 12 months) and mean depression score (at 6 months and 12 months). Data analyses were done according to intention-to-treat principles, accounting for missing data, and adjusted for outcome baseline scores. This trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN 12614001306606. Findings: Between Jan 16, and Aug 28, 2015, 584 patients registered for the study and were assessed for eligibility. 422 eligible participants were randomly allocated to the intervention group (227 patients) or control group (195 patients). 179 (79%) participants in the intervention group and 156 (80%) participants in the control group completed 12-month follow-up. Mean self-efficacy at 6 months and 12 months was lower for participants in the intervention group than for participants in the control group, although this did not meet the prespecified mean difference (6 months: 27·5 [SD 5·1] vs 28·1 [4·4], imputed mean difference 1·3 [95% CI 0·3 to 2·3]; 12 months: 27·8 [SD 5·4] vs 29·0 [5·0], imputed mean difference 1·6 [95% CI 0·5 to 2·7]). We found no difference between groups in depressive symptoms at 6 months or 12 months (6 months: 22·5 [SD 17·1] vs 24·2 [17·2], imputed mean difference -0·3 [95% CI -3·5 to 3·0]; 12 months: 21·9 [SD 19·3] vs 21·5 [19·3], imputed mean difference -1·9 [95% CI -5·6 to 1·7]). Qualitative findings indicated that participants found the intervention supportive and a motivation for action. Interpretation: Our findings highlight the need for further research, development, and refinement of online interventions for women experiencing intimate partner violence, particularly into the duration needed for interventions. Although we detected no meaningful differences between groups, our qualitative results indicated that some women find an online tool a helpful source of motivation and support. Funding: Australian Research Council.

The Lancet. Public health · randomised controlled trial · 43 citationsread the source →

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

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

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

Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial.

Background: New treatments with new mechanisms are urgently needed for people with schizophrenia. Xanomeline is a dual M1 and M4-preferring muscarinic receptor agonist that does not block D2 dopamine receptors, unlike all currently approved treatments for schizophrenia. Xanomeline-trospium (KarXT) combines xanomeline with the peripherally restricted muscarinic receptor antagonist trospium chloride with the goal of ameliorating xanomeline-related adverse events associated with peripheral muscarinic receptors. The EMERGENT-2 trial aimed to assess the efficacy and safety of KarXT in people with schizophrenia experiencing acute psychosis. Methods: EMERGENT-2 was a randomised, double-blind, placebo-controlled, flexible-dose, 5-week, inpatient, phase 3 trial in people with schizophrenia. Participants were adults aged 18-65 years with a diagnosis of schizophrenia who had a recent worsening of psychosis warranting hospital admission, a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher, and a Clinical Global Impression-Severity score of 4 or higher. The participants were recruited from 22 inpatient sites in the USA, and were randomly assigned (1:1) to KarXT or placebo twice per day. Participants randomly assigned to KarXT received 50 mg xanomeline and 20 mg trospium twice per day for the first 2 days and then 100 mg xanomeline and 20 mg trospium twice per day for days 3-7. Beginning on day 8, KarXT dosing was flexible with an optional increase to 125 mg xanomeline and 30 mg trospium twice per day and the option to return to 100 mg xanomeline and 20 mg trospium based on tolerability. The primary endpoint was change from baseline to week 5 in PANSS total score. Efficacy analyses used the modified intention-to-treat population (all randomly assigned participants who received at least one trial medication dose and had at least one post-baseline PANSS assessment). Least squares mean change from baseline, SE, and least squares mean difference between the KarXT and placebo groups at week 5, along with the 95% CI and two-sided p values were calculated for the primary and secondary continuous efficacy endpoints. Safety analyses included all participants receiving at least one trial medication dose and used descriptive statistics. This trial is registered with ClinicalTrials.gov (NCT04659161). Findings: From Dec 16, 2020, to April 13, 2022, of 407 people who were screened, 252 participants meeting enrolment criteria were randomly assigned to the KarXT (n=126) or placebo (n=126). Baseline PANSS total scores were 98·3 (KarXT; n=126) and 97·9 (placebo; n=125). The trial met the primary endpoint with a mean change from baseline to week 5 in PANSS total score that favoured KarXT (-21·2 points, SE 1·7) versus placebo (-11·6 points, 1·6; least squares mean difference -9·6; 95% CI -13·9 to -5·2; p<0·0001, Cohen's d effect size=0·61). All secondary endpoints were also met, and favoured KarXT versus placebo (p<0·05). The most common adverse events with KarXT versus placebo were constipation (27 [21%] vs 13 [10%]), dyspepsia (24 [19%] vs 10 [8%]), headache (17 [14%] vs 15 [12%]), nausea (24 [19%] vs seven [6%]), vomiting (18 [14%] vs one [1%]), hypertension (12 [10%] vs one [1%]), dizziness (11 [9%] vs four [3%]), gastro-oesophageal reflux disease (eight [6%] vs zero [0%]), and diarrhoea (seven [6%] vs four [3%]). Treatment-emergent adverse event rates of extrapyramidal motor symptoms (KarXT, zero [0%] vs placebo, zero [0%]), akathisia (one [1%] vs one [1%]), weight gain (zero [0%] vs one [1%]), and somnolence (six [5%] vs five [4%]) were similar between the KarXT and placebo groups, as were adverse event-related discontinuation rates (nine [7%] vs seven [6%]). Interpretation: In the EMERGENT-2 trial, KarXT was effective in reducing positive and negative symptoms and was generally well tolerated. These results support the potential for KarXT to represent a new class of effective and well tolerated antipsychotic medicines based on activating muscarinic receptors, not the D2 dopamine receptor-blocking mechanism of all current antipsychotic medications. Results from additional trials, including the identical EMERGENT-3 trial and the 52-week, open-label EMERGENT-4 and EMERGENT-5 trials, will provide additional information on the efficacy and safety of KarXT in people with schizophrenia. Funding: Karuna Therapeutics.

Lancet (London, England) · randomised controlled trial · 144 citationsread the source →

Affect-Focused Psychodynamic Internet-Based Therapy for Adolescent Depression: Randomized Controlled Trial.

Background: Adolescent depression is one of the largest health issues in the world and there is a pressing need for effective and accessible treatments. Objective: This trial examines whether affect-focused internet-based psychodynamic therapy (IPDT) with therapist support is more effective than an internet-based supportive control condition on reducing depression in adolescents. Methods: The trial included 76 adolescents (61/76, 80% female; mean age 16.6 years), self-referred via an open access website and fulfilling criteria for major depressive disorder. Adolescents were randomized to 8 weeks of IPDT (38/76, 50%) or supportive control (38/76, 50%). The primary outcome was self-reported depressive symptoms, measured with the Quick Inventory of Depressive Symptomatology for Adolescents (QIDS-A17-SR). Secondary outcomes were anxiety severity, emotion regulation, self-compassion, and an additional depression measure. Assessments were made at baseline, postassessment, and at 6 months follow-up, in addition to weekly assessments of the primary outcome measure as well as emotion regulation during treatment. Results: IPDT was significantly more effective than the control condition in reducing depression (d=0.82, P=.01), the result of which was corroborated by the second depression measure (d=0.80, P<.001). IPDT was also significantly more effective in reducing anxiety (d=0.78, P<.001) and increasing emotion regulation (d=0.97, P<.001) and self-compassion (d=0.65, P=.003). Significantly more patients in the IPDT group compared to the control group met criteria for response (56% vs 21%, respectively) and remission (35% vs 8%, respectively). Results on depression and anxiety symptoms were stable at 6 months follow-up. On average, participants completed 5.8 (SD 2.4) of the 8 modules. Conclusions: IPDT may be an effective intervention to reduce adolescent depression. Further research is needed, including comparisons with other treatments. Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN) 16206254; http://www.isrctn.com/ISRCTN16206254.

Journal of medical Internet research · randomised controlled trial · 50 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 →

Effect of Sleep Extension on Objectively Assessed Energy Intake Among Adults With Overweight in Real-life Settings: A Randomized Clinical Trial.

Importance: Short sleep duration has been recognized as a risk factor for obesity. Whether extending sleep duration may mitigate this risk remains unknown. Objective: To determine the effects of a sleep extension intervention on objectively assessed energy intake, energy expenditure, and body weight in real-life settings among adults with overweight who habitually curtailed their sleep duration. Design, setting, and participants: This single-center, randomized clinical trial was conducted from November 1, 2014, to October 30, 2020. Participants were adults aged 21 to 40 years with a body mass index (calculated as weight in kilograms divided by height in meters squared) between 25.0 and 29.9 and had habitual sleep duration of less than 6.5 hours per night. Data were analyzed according to the intention-to-treat principle. Interventions: After a 2-week habitual sleep period at baseline, participants were randomized to either an individualized sleep hygiene counseling session that was intended to extend their bedtime to 8.5 hours (sleep extension group) or to continue their habitual sleep (control group). All participants were instructed to continue daily routine activities at home without any prescribed diet or physical activity. Main outcomes and measures: The primary outcome was change in energy intake from baseline, which was objectively assessed as the sum of total energy expenditure and change in body energy stores. Total energy expenditure was measured by the doubly labeled water method. Change in body energy stores was computed using regression of daily home weights and body composition changes from dual-energy x-ray absorptiometry. Sleep duration was monitored by actigraphy. Changes from baseline were compared between the 2 groups using intention-to-treat analysis. Results: Data from 80 randomized participants (mean [SD] age, 29.8 [5.1] years; 41 men [51.3%]) were analyzed. Sleep duration was increased by approximately 1.2 hours per night (95% CI, 1.0 to 1.4 hours; P < .001) in the sleep extension group vs the control group. The sleep extension group had a significant decrease in energy intake compared with the control group (-270 kcal/d; 95% CI, -393 to -147 kcal/d; P < .001). The change in sleep duration was inversely correlated with the change in energy intake (r = -0.41; 95% CI, -0.59 to -0.20; P < .001). No significant treatment effect in total energy expenditure was found, resulting in weight reduction in the sleep extension group vs the control group. Conclusions and relevance: This trial found that sleep extension reduced energy intake and resulted in a negative energy balance in real-life settings among adults with overweight who habitually curtailed their sleep duration. Improving and maintaining healthy sleep duration over longer periods could be part of obesity prevention and weight loss programs. Trial registration: ClinicalTrials.gov Identifier: NCT02253368.

JAMA internal medicine · randomised controlled trial · 109 citationsread the source →

Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial.

Background: Patients with space-occupying hemispheric infarctions have a poor prognosis, with case fatality rates of up to 80%. In a pooled analysis of randomised trials, surgical decompression within 48 h of stroke onset reduced case fatality and improved functional outcome; however, the effect of surgery after longer intervals is unknown. The aim of HAMLET was to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction. Methods: Patients with space-occupying hemispheric infarction were randomly assigned within 4 days of stroke onset to surgical decompression or best medical treatment. The primary outcome measure was the modified Rankin scale (mRS) score at 1 year, which was dichotomised between good (0-3) and poor (4-6) outcome. Other outcome measures were the dichotomy of mRS score between 4 and 5, case fatality, quality of life, and symptoms of depression. Analysis was by intention to treat. This trial is registered, ISRCTN94237756. Findings: Between November, 2002, and October, 2007, 64 patients were included; 32 were randomly assigned to surgical decompression and 32 to best medical treatment. Surgical decompression had no effect on the primary outcome measure (absolute risk reduction [ARR] 0%, 95% CI -21 to 21) but did reduce case fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction), DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke onset, surgical decompression reduced poor outcome (ARR 16%, -0.1 to 33) and case fatality (ARR 50%, 34 to 66). Interpretation: Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset. The decision to perform the operation should depend on the emphasis patients and relatives attribute to survival and dependency.

The Lancet. Neurology · meta-analysis · 608 citationsread the source →

Adherence to varenicline in the COMPASS smoking cessation intervention trial.

Introduction: Patient adherence to smoking cessation medications can impact their effectiveness. It is important to understand the extent to which prescribed medications are actually taken by smokers, how this influences smoking cessation outcomes, and what factors may influence adherence. Methods: Smokers recruited from a large health plan were randomized to receive different modes of cessation counseling in combination with varenicline (Swan, G. E., McClure, J. B., Jack, L. M., Zbikowski, S. M., Javitz, H. S., Catz, S. L., et al. 2010.Behavioral counseling and varenicline treatment for smoking cessation. American Journal of Preventive Medicine, 38, 482-490). One thousand one hundred and sixty-one participants were mailed a 28-day varenicline supply when they set a quit date and were able to request up to two refills from the health plan pharmacy at no cost. Pharmacy fill records were obtained and telephone surveys completed at baseline, 21 days, 12 weeks, and 6 months post target quit date. Results: Good adherence to varenicline (≥80% of days taken) was associated with a twofold increase in 6-month quit rates compared with poor adherence (52% vs. 25%). Smokers were more likely than nonsmokers to stop varenicline early. Purposeful nonadherence was associated with smoking at 12 weeks and was predicted in multivariate analyses by age, gender, adherence self-efficacy, and initial medication side effect severity. Conclusions: Innovative methods for increasing adherence to smoking cessation medications are needed, particularly early in the quit process. Simple metrics of adherence such as number of days cessation medication is taken can and should be routinely incorporated in effectiveness trials and reported to advance future attempts to understand and reduce nonadherence.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · randomised controlled trial · 93 citationsread the source →

A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.

Context: Existing therapies for major depression have a lag of onset of action of several weeks, resulting in considerable morbidity. Exploring pharmacological strategies that have rapid onset of antidepressant effects within a few days and that are sustained would have an enormous impact on patient care. Converging lines of evidence suggest the role of the glutamatergic system in the pathophysiology and treatment of mood disorders. Objective: To determine whether a rapid antidepressant effect can be achieved with an antagonist at the N-methyl-D-aspartate receptor in subjects with major depression. Design: A randomized, placebo-controlled, double-blind crossover study from November 2004 to September 2005. Setting: Mood Disorders Research Unit at the National Institute of Mental Health. Patients Eighteen subjects with DSM-IV major depression (treatment resistant). Interventions: After a 2-week drug-free period, subjects were given an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days, a week apart. Subjects were rated at baseline and at 40, 80, 110, and 230 minutes and 1, 2, 3, and 7 days postinfusion. Main Outcome Measure Changes in scores on the primary efficacy measure, the 21-item Hamilton Depression Rating Scale. Results: Subjects receiving ketamine showed significant improvement in depression compared with subjects receiving placebo within 110 minutes after injection, which remained significant throughout the following week. The effect size for the drug difference was very large (d = 1.46 [95% confidence interval, 0.91-2.01]) after 24 hours and moderate to large (d = 0.68 [95% confidence interval, 0.13-1.23]) after 1 week. Of the 17 subjects treated with ketamine, 71% met response and 29% met remission criteria the day following ketamine infusion. Thirty-five percent of subjects maintained response for at least 1 week. Conclusions: Robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week.

Archives of general psychiatry · randomised controlled trial · 2568 citationsread the source →

Folate Augmentation of Treatment--Evaluation for Depression (FolATED): randomised trial and economic evaluation.

Background: Folate deficiency is associated with depression. Despite the biological plausibility of a causal link, the evidence that adding folate enhances antidepressant treatment is weak. Objectives: (1) Estimate the clinical effectiveness and cost-effectiveness of folic acid as adjunct to antidepressant medication (ADM). (2) Explore whether baseline folate and homocysteine predict response to treatment. (3) Investigate whether response to treatment depends on genetic polymorphisms related to folate metabolism. Design: FolATED (Folate Augmentation of Treatment - Evaluation for Depression) was a double-blind and placebo-controlled, but otherwise pragmatic, randomised trial including cost-utility analysis. To yield 80% power of detecting standardised difference on the Beck Depression Inventory version 2 (BDI-II) of 0.3 between groups (a 'small' effect), FolATED trialists sought to analyse 358 participants. To allow for an estimated loss of 21% of participants over three time points, we planned to randomise 453. Settings: Clinical - Three centres in Wales - North East Wales, North West Wales and Swansea. Trial management - North Wales Organisation for Randomised Trials in Health in Bangor University. Biochemical analysis - University Hospital of Wales, Cardiff. Genetic analysis - University of Liverpool. Participants: Four hundred and seventy-five adult patients presenting to primary or secondary care with confirmed moderate to severe depression for which they were taking or about to start ADM, and able to consent and complete assessments, but not (1) folate deficient, vitamin B12 deficient, or taking folic acid or anticonvulsants; (2) misusing drugs or alcohol, or suffering from psychosis, bipolar disorder, malignancy or other unstable or terminal illness; (3) (planning to become) pregnant; or (4) participating in other clinical research. Interventions: Once a day for 12 weeks experimental participants added 5 mg of folic acid to their ADM, and control participants added an indistinguishable placebo. All participants followed pragmatic management plans initiated by a trial psychiatrist and maintained by their general medical practitioners. Main outcome measures: Assessed at baseline, and 4, 12 and 25 weeks thereafter, and analysed by 'area under curve' (main); by analysis of covariance at each time point (secondary); and by multi-level repeated measures (sensitivity analysis): Mental health - BDI-II (primary), Clinical Global Impression (CGI), Montgomery-Åsberg Depression Rating Scale (MADRS), UKU side effects scale, and Mini International Neuropsychiatric Interview (MINI) suicidality subscale; General health - UK 12-item Short Form Health Survey (SF-12), European Quality of Life scale - 5 Dimensions (EQ-5D); Biochemistry - serum folate, B12, homocysteine; Adherence - Morisky Questionnaire; Economics - resource use. Results: Folic acid did not significantly improve any of these measures. For example it gained a mean of just 2.9 quality-adjusted life-days [95% confidence interval (CI) from -12.7 to 7.0 days] and saved a mean of just £48 (95% CI from -£292 to £389). In contrast it significantly reduced mental health scores on the SF-12 by 3.0% (95% CI from -5.2% to -0.8%). Conclusions: The FolATED trial generated no evidence that folic acid was clinically effective or cost-effective in augmenting ADM. This negative finding is consistent with improving understanding of the one-carbon folate pathway suggesting that methylfolate is a better candidate for augmenting ADM. Hence the findings of FolATED undermine treatment guidelines that advocate folic acid for treating depression, and suggest future trials of methylfolate to augment ADM. Trial registration: Current Controlled Trials ISRCTN37558856. Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 48. See the HTA programme website for further project information.

Health technology assessment (Winchester, England) · randomised controlled trial · 34 citationsread the source →

Changing eating behaviours to treat childhood obesity in the community using Mandolean: the Community Mandolean randomised controlled trial (ComMando)--a pilot study.

Background: Around one in five children in England is obese when they leave primary school. Thus far, it has not been demonstrated that primary care interventions to manage childhood obesity can achieve significant weight reduction. Training obese children to eat more slowly as an adjunct to other healthy lifestyle behaviour change has been shown to increase weight reduction in a hospital setting. Objectives: This pilot study aimed to test recruitment strategies, treatment adherence, clinic attendance and participants' experiences of using a device [Mandolean® (previously Mandometer®, Mikrodidakt AB, Lund, Sweden)] to slow down speed of eating as an adjunct to dietary and activity advice in treating obesity in primary school-aged children. Design: A two-arm, parallel, randomised controlled trial with a qualitative study embedded within the pilot. Randomisation occurred after informed consent and baseline measures were collected. Participants were randomised by the Bristol Randomised Trials Collaboration randomisation service with allocation stratified by hub and minimised by age of the child, gender, and baseline body mass index (BMI) standard deviation score (BMI z-value) of the child, and by BMI of the study parent (obese/not obese). Setting: General practices across Bristol, North Somerset and South Gloucestershire primary care trusts. Participants: Children (BMI ≥ 95th percentile) aged 5-11 years and their families. Intervention: Standard care comprised dietary and activity advice by trained practice nurses. Adjunctive Mandolean training (the intervention) educated participants to eat meals more slowly and to rate levels of fullness (satiety). Mandolean is a small computer device attached to a weighing scale that provides visual and oral feedback during meals while generating a visual representation of levels of satiety during the meal. Participants were encouraged to eat their main meal each day from the Mandolean. One parent was also given a Mandolean to use when eating with the child. Outcome measures: Outcomes for the pilot were recruitment of 36 families to the trial in the 9-month pilot phase, that meals would be eaten at least five times a week off a Mandolean by 90% of patients randomised to the intervention arm, that 80% of patients in both arms would attend the weight management clinic appointment 3 months post randomisation and that > 60% of children using Mandolean would demonstrate a reduction in speed of eating from baseline within 3 months of randomisation. Results: None of the criteria for progression to the main trial were reached. Despite numerous pathways being available for referral, only 21 (13 to standard care, eight to intervention arm; 58%) of the target 36 families were recruited in the pilot phase. Less than 20% of those randomised to Mandolean used the device at least five times a week. The > 60% target for slowing down of eating speed by 3 months was unmet. Attendance at the weight management clinic in general practice hubs for both arms of the study at 3 months was 44% against a target of 80%. Conclusions: This pilot trial failed to meet its objectives in terms of recruitment, treatment adherence, demonstration of a reduction in speed of eating in sufficient numbers of children, and attendance at follow-up appointments. Despite a high prevalence of childhood obesity in the geographical area and practices signing up for the trial, this study, like many others, demonstrates a failure of families to engage with and respond to primary care weight management interventions. We need to understand why the target population seems inured to the health message that childhood obesity is a significant health-care issue and identify the barriers to seeking help and then acting on positive health behaviour retraining. Only when we have fully understood the general public's perceptions of childhood obesity and have identified ways of engaging target populations can we hope to develop interventions that can work in a primary or community-based setting. Trial registration: Current Controlled Trials ISRCTN90561114. Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 47. See the NIHR Journals Library website for further project information.

Health technology assessment (Winchester, England) · randomised controlled trial · 31 citationsread the source →

Effect of peer support on prevention of postnatal depression among high risk women: multisite randomised controlled trial.

Objective: To evaluate the effectiveness of telephone based peer support in the prevention of postnatal depression. Design: Multisite randomised controlled trial. Setting: Seven health regions across Ontario, Canada. Participants: 701 women in the first two weeks postpartum identified as high risk for postnatal depression with the Edinburgh postnatal depression scale and randomised with an internet based randomisation service. Intervention: Proactive individualised telephone based peer (mother to mother) support, initiated within 48-72 hours of randomisation, provided by a volunteer recruited from the community who had previously experienced and recovered from self reported postnatal depression and attended a four hour training session. Main outcome measures: Edinburgh postnatal depression scale, structured clinical interview-depression, state-trait anxiety inventory, UCLA loneliness scale, and use of health services. Results: After web based screening of 21 470 women, 701 (72%) eligible mothers were recruited. A blinded research nurse followed up more than 85% by telephone, including 613 at 12 weeks and 600 at 24 weeks postpartum. At 12 weeks, 14% (40/297) of women in the intervention group and 25% (78/315) in the control group had an Edinburgh postnatal depression scale score >12 (chi(2)=12.5, P<0.001; number need to treat 8.8, 95% confidence interval 5.9 to 19.6; relative risk reduction 0.46, 95% confidence interval 0.24 to 0.62). There was a positive trend in favour of the intervention group for maternal anxiety but not loneliness or use of health services. For ethical reasons, participants identified with clinical depression at 12 weeks were referred for treatment, resulting in no differences between groups at 24 weeks. Of the 221 women in the intervention group who received and evaluated their experience of peer support, over 80% were satisfied and would recommend this support to a friend. Conclusion: Telephone based peer support can be effective in preventing postnatal depression among women at high risk. Trial registration: ISRCTN 68337727.

BMJ (Clinical research ed.) · randomised controlled trial · 215 citationsread the source →

Quebec Health-Related Quality-of-Life Population Norms Using the EQ-5D-5L: Decomposition by Sociodemographic Data and Health Problems.

Objectives: Population norms for the EQ-5D-5L were published in Canada but only for Alberta province. The purpose of this study was to derive Quebec population norms from the EQ-5D-5L. Methods: The data came from a larger study conducted between September 2016 and March 2018 using elicitation techniques for a quality-adjusted life-year project. The online survey was distributed randomly in the province of Quebec. To best describe the entire population, data were stratified by various sociodemographic characteristics such as age, gender, urban and rural populations, whether disadvantaged or not, immigrant or nonimmigrant, and health problems. Results: A total of 2704 (53.8%) respondents completed the EQ-5D-5L. Mean (95% confidence interval) and median (interquartile range) utility scores were 0.824 (0.818-0.829) and 0.867 (0.802-0.911), respectively. The EQ-VAS scores were estimated at 75.9 (75.2-76.6) and 80 (69-90). Subjects with lower scores were those who had a low or high body mass index; were smokers; were single, divorced, or widowed; had no children; were unemployed or sick; had lower education or lower annual income; and had a family or personal history of serious illness. Immigrants had higher scores. There was no difference in gender and urban or rural population. The score logically decreased with worsening health status, from a mean score of 0.896 (0.884-0.908) to 0.443 (0.384-0.501; P < .0001. Similar results were observed for subjects' satisfaction with their health or life. Subjects with lower scores were less willing to take risks. Subjects who declared they were affected by health problems presented significant lower utility scores, ranging from 0.554 (nervous problem) to 0.750 (cancer), compared with those without health problems (0.871; confidence interval: 0.867-0.876). Conclusion: This is the first study to present utility score norms for EQ-5D-5L for the Quebec population. These results will be useful for comparison with quality-adjusted life-year studies to better interpret their results. Moreover, utility norms were provided for 21 health problems, which was rarely done.

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research · cohort or longitudinal · 59 citationsread the source →

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

Background: We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine. Methods: Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period. Subjects were asked to self-treat at moderate or severe pain, or after 20 minutes of mild pain. Results: Of 30 enrolled patients (25 females, five males, median age 39), two treated no attacks, and one treated aura only, leaving a Full Analysis Set of 27 treating 80 attacks with pain. An adverse event was reported in 13 patients, notably: neck twitching (n = 1), raspy voice (n = 1) and redness at the device site (n = 1). No unanticipated, serious or severe adverse events were reported. The pain-free rate at two hours was four of 19 (21%) for the first treated attack with a moderate or severe headache at baseline. For all moderate or severe attacks at baseline, the pain-free rate was 12/54 (22%). Conclusions: nVNS may be an effective and well-tolerated acute treatment for migraine in certain patients.

Cephalalgia : an international journal of headache · clinical trial · 140 citationsread the source →

Prodromal psychosis screening in adolescent psychiatry clinics.

Background: Research has identified a syndrome conferring ultra-high risk (UHR) for psychosis, although UHR interviews require intensive staff training, time and patient burden. Previously, we developed the Prodromal Questionnaire (PQ) to screen more efficiently for UHR syndromes. Aims: This study examined the concurrent validity of the PQ against UHR status and preliminary predictive validity for later psychotic disorder. Method: We assessed a consecutive patient sample of 408 adolescents who presented to psychiatry clinics in Helsinki, Finland, seeking mental health treatment, including 80 participants who completed the Structured Interview for Prodromal Syndromes (SIPS). Results: A cut-off score of 18 or more positive symptoms on the PQ predicted UHR diagnoses on the SIPS with 82% sensitivity and 49% specificity. Three of 14 (21%) participants with high PQ scores and SIPS UHR diagnoses developed full psychotic disorders within 1 year. Conclusions: Using the PQ and SIPS together can be an efficient two-stage screening process for prodromal psychosis in mental health clinics.

Early intervention in psychiatry · cohort or longitudinal · 50 citationsread the source →

Autism Spectrum Disorder: A Review.

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

JAMA · review · 467 citationsread the source →

Post-traumatic Stress Disorder.

Unexpected extreme sudden traumatic stressor may cause post-traumatic stress disorder (PTSD). Important traumatic events include war, violent personal assault (e.g., sexual assault, and physical attack), being taken hostage or kidnapped, confinement as a prisoner of war, torture, terrorist attack, severe car accidents, and natural disasters. In childhood age sexual abuse or witnessing serious injuries or unexpected death of a beloved one are among important traumatic events.PTSD can be categorized into two types of acute and chronic PTSD: if symptoms persist for less than three months, it is termed "acute PTSD," otherwise, it is called "chronic PTSD." 60.7% of men and 51.2% of women would experience at least one potentially traumatic event in their lifetime. The lifetime prevalence of PTSD is significantly higher in women than men. Lifetime prevalence of PTSD varies from 0.3% in China to 6.1% in New Zealand. The prevalence of PTSD in crime victims are between 19% and 75%; rates as high as 80% have been reported following rape. The prevalence of PTSD among direct victims of disasters was reported to be 30%-40%; the rate in rescue workers was 10%-20%. The prevalence of PTSD among police, fire, and emergency service workers ranged from 6%-32%. An overall prevalence rate of 4% for the general population, the rate in rescue/recovery occupations ranged from 5% to 32%, with the highest rate reported in search and rescue personnel (25%), firefighters (21%), and workers with no prior training for facing disaster. War is one of the most intense stressors known to man. Armed forces have a higher prevalence of depression, anxiety disorders, alcohol abuse and PTSD. High-risk children who have been abused or experienced natural disasters may have an even higher prevalence of PTSD than adults. Female gender, previous psychiatric problem, intensity and nature of exposure to the traumatic event, and lack of social support are known risk factors for work-related PTSD. Working with severely ill patients, journalists and their families, and audiences who witness serious trauma and war at higher risk of PTSD.The intensity of trauma, pre-trauma demographic variables, neuroticism and temperament traits are the best predictors of the severity of PTSD symptoms. About 84% of those suffering from PTSD may have comorbid conditions including alcohol or drug abuse; feeling shame, despair and hopeless; physical symptoms; employment problems; divorce; and violence which make life harder. PTSD may contribute to the development of many other disorders such as anxiety disorders, major depressive disorder, substance abuse/dependency disorders, alcohol abuse/dependence, conduct disorder, and mania. It causes serious problems, thus its early diagnosis and appropriate treatment are of paramount importance.

The international journal of occupational and environmental medicine · review · 123 citationsread the source →

The Management of Preoperative Anxiety in Children: An Update

Anxiety in children undergoing surgery is characterized by subjective feelings of tension, apprehension, nervousness, and worry that may be expressed in various forms (1). Postoperative maladaptive behaviors, such as new onset enuresis, feeding difficulties, apathy and withdrawal, and sleep disturbances, may also result from anxiety before surgery. In fact, studies have indicated that up to 60% of all children undergoing surgery may present with negative behavioral changes at 2 wk postoperatively (1,2). Variables such as age, temperament, and anxiety of the child and parent in the preoperative holding area have been identified as predictors for these behavioral changes (1). Extreme anxiety during induction of anesthesia is also associated with an increase of these postoperative negative behavioral changes (3). In addition to behavioral manifestations, preoperative anxiety activates the human stress response, leading to increased serum cortisol, epinephrine, and natural killer cell activity (4,5). This stress response can be activated by many different noxious stimuli including fear, anxiety, pain, cold, major surgery, and infection. The main components of the stress system are the corticotropin-releasing hormone and the locus ceruleus-norepinephrine/autonomic systems and their peripheral effectors, the hypothalamic pituitary-adrenal axis and the limbs of the autonomic system (5). There is also evidence for a bidirectional communication between the neuroendocrine system and the immune system. Stress activates the hypothalamic pituitary-adrenal axis, increases circulating glucocorticoids, and is associated with alterations of immune function and susceptibility to infection and neoplastic disease (6). The human response to surgical stress is characterized by a series of hormonal, immunological, and metabolic changes that together constitute the global surgical stress response (7,8). This perioperative response is considered a homeostatic mechanism for adapting to the perioperative injury. The effects of the surgical stress response, however, may be detrimental: neuroendocrine hormones (e.g., cortisol, catecholamines) and cytokines (e.g., interleukin-6) provoke a negative nitrogen balance and catabolism, delay wound healing, and cause postoperative immunosuppression (7,8). Children are particularly vulnerable to the global surgical stress response because of limited energy reserves, larger brain masses, and obligatory glucose requirements (9). Because acute psychological stress, such as preoperative anxiety, is associated with immediate stress hormone release, the contribution of perioperative psychological factors to the global perioperative stress response cannot be ignored. In adults, increased preoperative anxiety is associated with poor postoperative behavioral and clinical recovery (10,11). As an indicator of the importance of preoperative anxiety, a panel of 72 anesthesiologists recently ranked various anesthesia low-morbidity clinical outcomes based on importance and frequency. The five clinical outcomes with the highest combined score were incisional pain, nausea, vomiting, preoperative anxiety, and discomfort from IV insertion (12). Thus, consensus is evident among anesthesiologists about the need to treat anxiety before surgery. In a modern epidemiological framework, diseases can be characterized in terms of risk factors, interventions, and outcomes. In this update, we will review preoperative anxiety in children using this conceptual framework (Fig. 1).Figure 1: Conceptual framework of perioperative anxiety. Revised from (72).The Psychobiology of Separation Learning to cope with separation from a parent is necessary for a child’s normal development (13). Separation experiences such as going to school facilitate normal psychological development and personality organization. Other separation experiences, such as perioperative separation, may precipitate confusion and anxiety. Between these two extremes, there are many separation experiences with varying degrees of psychobiological stress. In the first weeks of life, infants are able to discriminate among people, but will accept care and comfort from adults other than their parents (14). By 3 mo of age, however, infants begin to respond differently to familiar and unfamiliar people. Older infants smile more at familiar people and may even try to engage their attention (14). Separation anxiety usually begins at 7–8 mo of age and peaks around 1 yr of age. In part, separation anxiety represents the infant’s acquisition of new cognitive abilities and object permanence. The intensity of separation anxiety declines with age, largely because of increasing cognitive abilities and memory capacity. Frequently, however, the increase in abilities does not immunize toddlers and preschoolers against the stress and distress of separations. The extent to which separation is traumatic or evokes adaptive responses reflects an individual child’s developmental age, parenting experiences, genetic endowment, and environmental stability. For children with biologically based vulnerabilities, such as a sensitivity to novelty and transitions, even expected separations may impose a greater degree of stress than for less sensitive children (13). How parents help the child mediate a separation experience play a crucial role in the child’s acute and long-term responses. In the extreme, the parent may be unable to mediate the experience for the child because of limitations such as severe anxiety. How well children have been cared for up to the time of the separation also influences their response to the stressor. Children deprived of attention in the home are at increased risk for stress in response to separations. Thus, the extent to which separations evoke adaptive responses reflects an individual child’s genetics, personality, parenting, and previous life experiences. Preoperative Anxiety: Identification Identifying risk factors for development of preoperative anxiety is important, as more resources can be directed toward vulnerable children. Children 1–5 yr old are at the highest risk for developing extreme anxiety (1). This is not surprising considering the psychobiology of separation anxiety. Children who are shy or inhibited and those who have a high intelligence quotient and lack good adaptive abilities are also at increased risk (15). Previous surgery or hospitalization and poor response to visits to the pediatrician’s office are also predictors for the development of preoperative anxiety. Finally, parental anxiety has been identified as a predictor for increased child’s anxiety. Preoperative Anxiety: Behavioral Modalities Preoperative Preparation Programs Most studies suggest that preoperative preparation programs reduce anxiety and enhance coping in children (16). These behavioral preparation programs have evolved significantly over recent decades. In the 1960s, preparation programs were designed to provide an orientation tour and narrative information and facilitate trust between the hospital staff, the child, and the parent (16). In the 1970s, modeling techniques were developed where children indirectly experienced the perioperative course by role rehearsal using dolls or by viewing a video (17). These modeling techniques were augmented in the late 1980s with child life preparation and the teaching of coping skills (17). Currently, development of coping skills is considered the most effective preoperative preparation intervention, followed by modeling, play therapy, operating room tour, and printed material (18). Although experts favor teaching of coping skills, most preparation programs in the United States consist of an orientation tour and printed information (18). Although coping preparation has been associated with reduction of anxiety in the preoperative holding area, no differences were found among the various preparation programs during induction, in the recovery room period, or postoperatively (19). Thus, the cost-effectiveness of child life specialists may or may not be justified by an associated reduction in preoperative anxiety. Psychological preparation programs should be tailored to individual needs such as age, developmental stage, and previous experience (20). The priority of the age criterion relates to both the anxiety such exposure might generate and the length of time over which children can cope with anticipation. In addition, timing of the program before surgery is an important variable (20). Children aged ≥6 yr benefit most if they participate in a preparation program ≥5 days before surgery and benefit least if the program is given only 1 day before surgery. This phenomenon is related to the way that children in this age group process new information. Finally, a child who has previously undergone surgery or has been hospitalized may develop an exaggerated emotional response to an information-based preparation program (20). As increased parental anxiety results in increased child’s anxiety (1), there is a need for interventions that are designed specifically for parents. Cassady et al. (21) demonstrated that parental preoperative anxiety decreased after viewing an educational videotape. We suggest that more parental interventions need to be developed and that a child’s anxiety should be evaluated as an outcome. Preoperative Anxiety: Behavioral Modalities Parental Presence during Induction of Anesthesia. Parents and children prefer to stay together during medical procedures such as immunizations, dental treatment, and induction of anesthesia (22). Some data indicate, however, that parental presence during induction of anesthesia (PPIA) is allowed in 26% of US hospitals and is encouraged in only 8% of hospitals (23). In contrast, 28% of hospitals have no formal hospital policy and parental presence is against hospital policy for 32% of hospitals in the US. The smallest use of this induction technique was reported in the South-Central region and the highest in the Northwest and the Northeast (23). Interestingly, anesthesiologists from Great Britain (GB) encourage PPIA significantly more than anesthesiologists from the US (23,24). The reasons for these differences may include the use of different induction techniques, less concern about legal ramifications in GB, and a stronger demand for parental presence in GB. Economic issues such as operating room (OR) efficiency, infrastructure issues, lack of induction rooms and patchy preoperative educational programs, probably limit the availability of PPIA in the US. Potential benefits from PPIA include reducing the need for preoperative sedatives and avoiding the fear and anxiety that may occur on separation to the OR. Other benefits, such as increasing the child’s compliance during induction, remain controversial. Objections to PPIA include concern about disruption of the OR routine, crowded ORs, and a possible adverse reaction of parents. In addition, increased parental anxiety can increase a child’s anxiety, prolong anesthetic induction, and place additional stress on the anesthesiologist. Although early observational studies suggested reduced anxiety if parents were present during induction (25), more recent randomized controlled trials indicate that routine parental presence is not beneficial (26–28). One study demonstrated that only children >4 yr of age, those who have a “calm” baseline personality, or those who have a parent with a “calm” baseline personality benefit from this intervention (26). When interpreting the results of these studies, however, it should be noted that the design of a randomized controlled study does not reflect the practice of all anesthesiologists. When data of survey studies are reviewed (23,24), it is noticed that most anesthesiologists use either PPIA or sedative premedication to treat preoperative anxiety. When sedative premedications were directly compared with PPIA, however, it was found that children receiving oral midazolam were significantly less anxious and more compliant during the induction process (27). A recent study examined whether a combination of PPIA and oral midazolam is more effective than oral midazolam alone (28). The investigators found that PPIA has no additive anxiolytic effects for children who received oral midazolam preoperatively. Parents who accompany their sedated children into the ORs, however, are significantly less anxious and more satisfied both with the separation process and with the overall anesthetic, nursing and surgical care provided (28). PPIA is also associated with important legal implications. Lewyn (29) described a case in which a mother was invited to accompany her son into an emergency treatment room. According to the court, the mother fainted and suffered an injury to the head. In its verdict the Illinois Supreme Court stated that a hospital, which allows a nonpatient to accompany a patient during treatment, does not have a duty to protect the nonpatient from fainting. However, if medical personnel invite the nonpatient to participate in the treatment, then the hospital has a legal responsibility toward the nonpatient. Interestingly, some hospitals in the US now require the parents to sign a written informed consent acknowledging the risk of being present during induction of anesthesia. We believe that future research interests should shift towards an emphasis on what parents actually do during induction of anesthesia, rather than simply on their presence. Allowing a parent into an OR without significant preparation may be counterproductive because some parent behaviors, such as criticism and commands, are associated with increased distress. Effective methods of training such as parental preparation programs can be developed for enhancing the effects of PPIA. Preoperative Anxiety: Pharmacological Modalities The reported rate of use of pharmacological modalities for the treatment of preoperative anxiety in the US varies widely among age groups and geographical locations (24). Premedicant sedative drugs are least often used with children <3 yr of age and most often used with adults <65 yr of age (25% vs 75%). Currently, the most commonly used sedative premedicant in the preoperative holding area is midazolam (85%), followed by ketamine (4%), transmucosal fentanyl (3%), and meperidine (2%) (Fig. 2). TABLETABLE The majority of children in the US are premedicated via the oral route (80%), followed by the intranasal route (8%), the IM route (6%), and the rectal route (3%).Figure 2: Types of premedicants used in the preoperative holding area (23).Table 1: Premedications Administered by the Oral RouteTable 2: Premedications Administered Transmucosally and RectallyMidazolam. Midazolam is a short-acting benzodiazepine that is very lipophilic at physiologic pH, which accounts for its rapid onset of action. Davis et al. (30) has demonstrated that intranasally administered midazolam in a dosage of 0.2–0.3 mg/kg in patients undergoing myringotomies led to satisfactory separation from parents and a satisfactory induction over 70% of the time and did not prolong recovery time and hospital discharge time. Midazolam administered intranasally is effective in reducing anxiety in children within 10–12 min (31). A major drawback of intranasally administered midazolam, however, is that at least 50% of children cry on administration because it transiently irritates the nasal passages. Midazolam can also be given as a nasal spray, which is effective in reducing procedural anxiety in children undergoing cancer therapy (32). Midazolam can be administrated sublingually at the same dosage as intranasally. Although sublingual administration of midazolam is associated with a decreased incidence of crying (18%), it may be difficult to prevent small children from either swallowing the midazolam or spitting it out immediately (33). Rectal administration of midazolam in doses of 0.5–1.0 mg/kg effectively reduces the anxiety of children before induction of anesthesia (34). Although the incidence of hiccups after IV midazolam is <2%, the incidence noted that in a recent study involving rectally administered midazolam was more than 20%(34). The investigators had no explanation as to the increased rate of hiccups other than the young age of the children, but they found that the hiccups were easily treated by ethyl chloride nasal spray (34). Orally administered midazolam (0.5 mg/kg) has been shown to significantly reduce preoperative anxiety in young children (27,28). Orally administered midazolam can be given in a dosage of 0.25 mg to 1.0 mg/kg up to total dose of 20 mg depending on the of surgery and the anxiety of the A and and midazolam in a of 2 in et al. examined different doses of the midazolam and found that 0.25 mg/kg in satisfactory and in a majority of patients within 20 This study also found that increasing the dose in an increase in the of patients with satisfactory and a time to onset of Other that the time for premedicated children from their parents is min with a sedative between 20 and min The of administered midazolam and in the discharge of patients is controversial. Although recent studies noted that administrated midazolam is not associated with a discharge two studies involving children undergoing that and recovery are in the children who oral midazolam study involving children who myringotomies using or anesthesia indicated that children who were given oral midazolam experienced significant in recovery time but no in discharge time from the hospital Finally, et al. have the of a combination of preoperative oral midazolam and The investigators found that requirements by and discharge was in children who had been given midazolam preoperatively. The investigators suggested that the increased postoperative may have been to of and midazolam on As indicated a significant of children experiences maladaptive behavioral changes after surgery (1). In children who were premedicated with oral midazolam had a significantly decreased incidence of negative behavioral changes during the first after surgery However, this study noted that by 2 wk postoperatively there were no significant differences between the midazolam and The mechanism by which midazolam the incidence of postoperative behavioral changes is not but it may be related to of the perioperative process Children who received a benzodiazepine for dental and were about the experience dental than children who were not about their dental This may be particularly important for children undergoing surgical in children after oral midazolam as early as min and anxiolytic effects are as early as min after administration This timing to onset of is of importance in surgery where the of is very Midazolam and can be with which The dose in children is mg/kg given IV in a of up to 1.0 mg Some children who are with will experience it is to for can also be intranasally in a dose of given by from a is a that is very which the a good for administration and Oral transmucosal fentanyl administered in the of a to a and as the was the first sedative by the and in for use in children. Oral transmucosal in and dosage is in a and given to children in the dosage of for sedative is often associated with which usually min after children begin to the children before induction of anesthesia does however, to decreased or with induction in young children In a small of can cause a leading to significant a in be present this is administered in children is associated with a incidence of postoperative and that is not easily by In fact, at least study was because of a very incidence of preoperative A significant of is that it the postoperative et al. reported that preoperative is as effective as IV fentanyl given for of postoperative in children undergoing is an that a of and from the of ketamine compared with other premedicants is that it less given in sedative doses A of ketamine as compared with other premedicants is the of increased and which can to can also cause and in children, which can parents if they are not informed about this increased incidence of postoperative is associated with preoperative administration of ketamine The effects are all dose related and can be with the use of a small dose of administered ketamine mg/kg) the time of onset of the of administered ketamine is also dose related with administered ketamine mg/kg) an onset of of min and ketamine leading to within 20 min administration may be associated with and during the postoperative recent studies have found that use of a benzodiazepine given to children undergoing ketamine did not the incidence of In addition, the incidence of postoperative and is no different in children receiving midazolam, or a combination of ketamine and midazolam together The IV preparation of ketamine can be with or to an oral of which is by most children. can be also be given intranasally rectally and IM mg/kg) care discharge time of children who received administered ketamine is reported not to be compared with administered midazolam provided that of surgery is than min administered IM in an emergency room however, was found to significantly delay discharge and increase compared with midazolam administered rectally or intranasally et al. reported that the combination of midazolam and ketamine administrated had a rate of satisfactory compared with with either oral was also found to be to IM and in children undergoing The provided and and there was less need for IV as compared with the IM is an first developed as an but found to have and sedative Orally administrated in a dose of anesthetic and for postoperative requirements by 50% in children premedicated with This in may be to the of as well as a administered is also as effective as administered fentanyl for postoperative in children undergoing The recovery of children who is to the recovery of children who oral but significantly less postoperative as compared with One major drawback for the use of as a sedative premedicant is its onset of action. has to be administered as early as min before surgery In children, is at min for administered and min for rectally administered for the research should on the development of sedatives that will be well have a very time for onset of and have of action. In addition, developed preoperative sedatives should such as and should anesthetic requirements and reduce postoperative Finally, new methods of sedative premedications should also be For of should be as well as oral transmucosal methods for other than usually at least 1 for effective serum of drugs to be is can significantly the of a and has been effective in fentanyl in adults within min at 2 Finally, the of treatment modalities such as should be research is in these The to for review of this

Anesthesia & Analgesia · review · 408 citationsread the source →

The impact of frailty on ICU and 30-day mortality and the level of care in very elderly patients (≥ 80 years).

Purpose: Very old critical ill patients are a rapid expanding group in the ICU. Indications for admission, triage criteria and level of care are frequently discussed for such patients. However, most relevant outcome studies in this group frequently find an increased mortality and a reduced quality of life in survivors. The main objective was to study the impact of frailty compared with other variables with regards to short-term outcome in the very old ICU population. Methods: A transnational prospective cohort study from October 2016 to May 2017 with 30 days follow-up was set up by the European Society of Intensive Care Medicine. In total 311 ICUs from 21 European countries participated. The ICUs included the first consecutive 20 very old (≥ 80 years) patients admitted to the ICU within a 3-month inclusion period. Frailty, SOFA score and therapeutic procedures were registered, in addition to limitations of care. For measurement of frailty the Clinical Frailty Scale was used at ICU admission. The main outcomes were ICU and 30-day mortality and survival at 30 days. Results: A total of 5021 patients with a median age of 84 years (IQR 81-86 years) were included in the final analysis, 2404 (47.9%) were women. Admission was classified as acute in 4215 (83.9%) of the patients. Overall ICU and 30-day mortality rates were 22.1% and 32.6%. During ICU stay 23.8% of the patients did not receive specific ICU procedures: ventilation, vasoactive drugs or renal replacement therapy. Frailty (values ≥ 5) was found in 43.1% and was independently related to 30-day survival (HR 1.54; 95% CI 1.38-1.73) for frail versus non-frail. Conclusions: Among very old patients (≥ 80 years) admitted to the ICU, the consecutive classes in Clinical Frailty Scale were inversely associated with short-term survival. The scale had a very low number of missing data. These findings provide support to add frailty to the clinical assessment in this patient group. Trial registration: ClinicalTrials.gov (ID: NCT03134807).

Intensive care medicine · 338 citationsread the source →

Decisional Satisfaction, Regret, and Conflict Among Parents of Infants with Neurologic Conditions.

Objective: To characterize decisional satisfaction, regret, and conflict among parents of critically ill infants with neurologic conditions. Study design: In this prospective cohort study, we enrolled parents of infants with neurologic conditions in the intensive care unit (ICU). Hospital discharge surveys included the validated Family Satisfaction with the ICU (FS-ICU) decision making subscale, Decision Regret Scale (DRS), and Decisional Conflict Scale (DCS). We defined high satisfaction with decision making as an FS-ICU score ≥75, high decisional regret/conflict as DRS/DCS score >25, and within-couple disagreement as a difference of at least 25 points between scores. Results: We enrolled 61 parents of 40 infants (n = 40 mothers, n = 21 fathers); 35 mothers and 15 fathers completed surveys. Most mothers reported high satisfaction with decision making (27 of 35; 77%) and low decision regret (28 of 35; 80%); 40% (14 of 35) reported high decisional conflict. Mothers and fathers reported higher decisional conflict in the domains of uncertainty and values clarity compared with the domain of effective decision making (Bonferroni-corrected P < .05). There were no differences in decision outcomes between paired mothers and fathers; however, within any given couple, there were numerous instances of disagreement (7 of 15 for decision regret and 5 of 15 for decisional conflict). Conclusions: Many parents experience decisional conflict even if they ultimately have high satisfaction and low regret, underscoring the need for decision aids targeting uncertainty and values clarity. Couples frequently experience different levels of decisional regret and conflict.

The Journal of pediatrics · 14 citationsread the source →

Enhancing reciprocal partner support to prevent perinatal depression and anxiety: a Delphi consensus study.

Background: Systematic reviews have established that partner support protects against perinatal mood problems. It is therefore a key target for interventions designed to prevent maternal and paternal depression and anxiety. Nonetheless, the extant literature is yet to be translated into specific actions that parents can implement. Prevention efforts aiming to facilitate reciprocal partner support within the couple dyad need to provide specific guidance on how partners can support one another to reduce their vulnerability to perinatal depression and anxiety. Method: Two panels of experts in perinatal mental health (21 consumer advocates and 39 professionals) participated in a Delphi consensus study to establish how partners can support one another to reduce their risk of developing depression and anxiety during pregnancy and the postpartum period. Results: A total of 214 recommendations on how partners can support each other were endorsed by at least 80 % of both panels as important or essential in reducing the risk of perinatal depression and anxiety. The recommendations were grouped under the following categories: becoming a parent, supporting each other through pregnancy and childbirth, communication, conflict, division of labor, practical support, emotional support, emotional closeness, sexual satisfaction, using alcohol and drugs, encouraging self-care, developing acceptance, and help-seeking. Conclusion: This study established consensus between consumers and professionals in order to produce a set of guidelines on how partners can support each other to prevent depression and anxiety during pregnancy and following childbirth. It is hoped that these guidelines will inform the development of perinatal depression and anxiety prevention efforts.

BMC psychiatry · 22 citationsread the source →

Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review.

Top-tier evidence on the safety/tolerability of 80 medications in children/adolescents with mental disorders has recently been reviewed in this jour-nal. To guide clinical practice, such data must be combined with evidence on efficacy and acceptability. Besides medications, psychosocial inter-ventions and brain stimulation techniques are treatment options for children/adolescents with mental disorders. For this umbrella review, we systematically searched network meta-analyses (NMAs) and meta-analyses (MAs) of randomized controlled trials (RCTs) evaluating 48 medications, 20 psychosocial interventions, and four brain stimulation techniques in children/adolescents with 52 different mental disorders or groups of mental disorders, reporting on 20 different efficacy/acceptability outcomes. Co-primary outcomes were disease-specific symptom reduction and all-cause discontinuation ("acceptability"). We included 14 NMAs and 90 MAs, reporting on 15 mental disorders or groups of mental disorders. Overall, 21 medications outperformed placebo regarding the co-primary outcomes, and three psychosocial interventions did so (while seven outperformed waiting list/no treatment). Based on the meta-analytic evidence, the most convincing efficacy profile emerged for amphetamines, methylphenidate and, to a smaller extent, behavioral therapy in attention-deficit/hyperactivity disorder; aripiprazole, risperidone and several psychosocial interventions in autism; risperidone and behavioral interventions in disruptive behavior disorders; several antipsychotics in schizophrenia spectrum disorders; fluoxetine, the combination of fluoxetine and cognitive behavioral therapy (CBT), and interpersonal therapy in depression; aripiprazole in mania; fluoxetine and group CBT in anxiety disorders; fluoxetine/selective serotonin reuptake inhibitors, CBT, and behavioral therapy with exposure and response prevention in obsessive-compulsive disorder; CBT in post-traumatic stress disorder; imipramine and alarm behavioral intervention in enuresis; behavioral therapy in encopresis; and family therapy in anorexia nervosa. Results from this umbrella review of interventions for mental disorders in children/adolescents provide evidence-based information for clinical decision making.

World psychiatry : official journal of the World Psychiatric Association (WPA) · 114 citationsread the source →

5-year mental health and eating pattern outcomes following bariatric surgery in adolescents: a prospective cohort study.

Background: Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. Methods: This was a non-randomised matched-control study in adolescents aged 13-18 years who had a BMI of 40 kg/m2 or higher, or 35 kg/m2 or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov (NCT00289705). Findings: Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI -7 to 16], p=0·4263) or after intervention (10% [-6 to 24], p=0·2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [-10 to 14], p=0·7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0·0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21·6 [95% CI 19·9 to 23·4]) relative to baseline (18·9 [17·4 to 20·4], p=0·0059), but overall mood (MACL score) was not (2·8 [2·7 to 2·9] at 5 years vs 2·7 [2·6 to 2·8] at baseline, p=0·0737). Binge eating was improved at 5 years (9·3 [7·4 to 11·2]) relative to baseline (15·0 [13·5 to 16·5], p<0·0001). Relative changes in BMI were not associated with the presence or absence of binge eating at baseline. Interpretation: Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery. Funding: Swedish Research Council, VINNOVA, Västra Götalandsregionen, ALF VG-region, Region Stockholm, Swedish Child Diabetes Foundation, Swedish Heart and Lung Foundation, Tore Nilsson's Foundation, SUS Foundations and Donations, Capio Research Foundation, and Mary von Sydow's Foundation.

The Lancet. Child & adolescent health · 44 citationsread the source →

Transitional Care Units: Greater Than the Sum of Their Parts

Introduction In 1981, alarmed at the trend of incident patients selecting in-center hemodialysis over home therapies, Northwest Kidney Centers (NWK) established the first “dialysis orientation unit” under the direction of Dr. Joel Eschbach (1). The orientation unit provided a 2-month stabilization program emphasizing modality and diet education, patient “rehabilitation,” and transitioning safely to home dialysis. What was the historically “low” rate of home hemodialysis uptake that spurred development of this program? 50%. Today, any dialysis organization would consider a 50% home therapy start rate a resounding success. In subsequent years, nephrologists learned hard lessons about the dangers posed to patients in the first year of dialysis, particularly those “crashing in.“ It is now understood that the first 90 days of dialysis remain a period of high cost, high hospitalization rates, and mortality (2). This finding is often attributed to a lack of or insufficient nephrology predialysis care (3). US Renal Data System information suggests nearly 40% of patients with ESKD initiate dialysis without adequate preparation (2). Despite efforts to improve these statistics, so-called “suboptimal starts,” patients initiating dialysis in a hospital or with a central venous catheter (CVC), predominate making up 80% of the incident dialysis cohort (2). A detailed review of the causes of this phenomenon is beyond the scope of this article; however, one underappreciated contributor to suboptimal starts is unexpected and rapid loss of GFR in established CKD immediately preceding dialysis initiation. This situation catches patient and physician unaware, precluding or abbreviating participation in pre-ESKD care. Estimates of the number of patients experiencing this scenario are hampered by a lack of predialysis kidney function data, but a recent retrospective study noted that approximately 50% of patients may enter dialysis this way (4). Another study of incident patients with ESKD followed previously in long-term CKD clinics compared those initiating dialysis with a CVC against patients with an existing fistula or graft. The CVC group experienced double the rate of GFR loss in the 6 months preceding dialysis compared with the fistula/graft group (5). These studies imply that a sizeable portion of patients, irrespective of predialysis nephrology care, may not have access to adequate preparation due to sudden rapid GFR decline. Such individuals require “rescue therapy” in their first weeks and months of dialysis to navigate what has been rightly described “the trauma of dialysis initiation” (6,7). Goals of Transitional Dialysis Care Transitional dialysis care, referring to the medical and psychosocial support provided during the peridialysis initiation period, may take many forms from simple programs where designated staff provide focused chairside education to physically separate dialysis units providing broad support services. Although terminology is still evolving, specialized units dedicated to the needs of incident patients may be termed “transitional care units” (TCUs). These units share many characteristics with existing home training programs, and therefore, many goals of a TCU will already be familiar to clinicians. Gentle medical stabilization of the patient who is new to dialysis In-depth education on modality, nutrition, and financial aspects of ESKD Provide emotional and psychologic support Provide a welcoming environment and education for caregivers/partners Provide “patient navigation” services to facilitate multiple appointments, such as access and transplant Provide a supportive, low-risk environment to sample home therapies Although patient-centered goals have been the primary driver for establishing TCUs, in the era of value-based care, these units may also represent a cost-effective quality improvement intervention. This is accomplished by adopting proven elements of existing programs, such as checklists, patient navigators, teaching methods, etc., and placing them under a single geographic and programmatic “roof.” In doing so, it is possible a TCU model can attain similar quality improvements, such as Decreased access placement latency times Improved transplant referral timing and volume Improved adoption of home therapies Decreased hospitalizations and mortality A typical transitional care program may last 4–8 weeks and involves all members of the interdisciplinary care team providing scheduled chairside teaching and enhanced educational activities. At program conclusion, patients should emerge with an understanding of all aspects of their disease, allowing for truly informed decisions in areas such as modality and transplant. Early support interventions have the potential to reduce disparities in home therapies and transplant by reducing provider modality bias in favor of patient choice. Historical Perspectives on Transitional Care The first documented example of a TCU (established as the “Dialysis Orientation Unit” at NWK) brought together distributed patient care activities and work flows. The goal was to “rehabilitate the patient,” promote self-care, and allow the patient to attain a quality of life as close as possible to their pre-ESKD self (1). The program featured a physically separate unit, high staff-to-patient ratio, and close collaboration with the home training group. Unit staff members were selected not only on the basis of clinical skill but also on the ability to empathize and educate. Primary nursing was a focus, with a now hard to imagine 1:2 nurse-to-patient ratio. All new patients began in the orientation unit—no cherry picking was allowed. In the first year, 93 patients completed the training curriculum and spent an average of 9 weeks in the program. Results were impressive: 62% of patients transitioned to the home dialysis training unit; 24% of patients, unable or unwilling to dialyze at home, transitioned to “limited care”—similar to today’s “in-center self-care,” and only 10% joined the general in-center population (1). Over the next decade, more medically complex patients began to enter dialysis, and the early results proved difficult to maintain. However, before its closing in the mid-1990s, this early TCU example attained a still impressive 25% uptake rate of home therapies (1). In the 2000s, large United States-based dialysis providers initiated dedicated quality improvement programs targeting incident patients. Although these programs included many elements of the dedicated TCU model, they did not use the separate physical plant component. Demonstrable improvements were observed in hard outcomes, such as access placement rates, hospitalizations, and mortality (8). Although modality education was a component of these programs, effects on home therapy uptake were not reported. In Canada, a number of hospital-based dialysis entities with a “home first” focus established TCUs with an emphasis on psychosocial support and meaningful modality education. One such example, Humber River Hospital’s TCU, reported results of 180 incident dialysis starts in a six-station dedicated unit. In their hands, home dialysis uptake rates more than doubled for participants in the TCU (56%) versus nonparticipants (21%) (9). More striking, patients with “unplanned” dialysis starts had a 50% home therapy uptake rate when funneled through the TCU. Today in the United States, TCUs are just beginning to take root, with only anecdotal outcome data available. One such program at Satellite Dialysis, termed “Optimal Transitions,” has described early results. Their TCU uses traditional education and psychosocial support program pillars but adds a new element—a 5-day per week dialysis schedule using home dialysis machines to provide a gentler break-in experience (10). The final weeks of the program conclude with a dedicated “self-care” phase, where patients are given hands-on training and time to experiment with home dialysis therapy. Conclusions Aside from transplantation, there is currently no single intervention in kidney disease that is as impactful as improving the transition from CKD to ESKD. Despite recent improvements in referral timing and the overall proportion of patients receiving pre-ESKD care, a substantial population of patients remains vulnerable to poor health outcomes and is deprived of meaningful modality choice at dialysis initiation due to lack of adequate support and education. A TCU provides the framework to both medically and emotionally support these patients. These units stitch together multiple proven interventions to provide a supportive medical home. Operationally, transitional units can scale as needed. A dialysis clinic with low-incident patient volumes may dedicate as few as one to two stations to transitional care and easily handle a year’s worth of incident patients. Although the intervention is intensive from the patient perspective, the program is limited to a unit’s new patients only. Staff and physicians are not overwhelmed by wholesale changes to dialysis operations, like those seen in more complex alternative payment models. The expected increased time commitment for the physician is akin to a couple of extra clinic visits per week. However promising early TCU results may be, clinical trials remain necessary to justify upfront investments in such units. Increases in home therapy adoption seem the most assured outcome; however, larger study populations are required to show improvements in hospitalization rates, mortality, and access placement. By bringing incident patients, providers, and proven interventions together in one location, the TCU model may prove greater than the sum of its parts. Disclosures Dr. Bowman is the principal investigator on a proposed multisite trial of the effect of the transitional care unit concept. NxStage Medical Inc. has agreed to provide data hosting for this trial. All other expenses are self-funded by the participating units.

Clinical Journal of the American Society of Nephrology · 27 citationsread the source →

Prevalence of depressive disorders and treatment in China: a cross-sectional epidemiological study.

Background: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012-15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. Methods: The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age-sex-residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. Findings: 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20-1·72] and 12-month prevalence OR 1·41 [1·12-1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68-3·38] and 12-month OR 2·80 [95% CI 1·88-4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39-2·51] and 12-month OR 1·85 [95% CI 1·40-2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. Interpretation: Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. Funding: National Health Commission and Ministry of Science and Technology of People's Republic of China. Translation: For the Chinese translation of the abstract see Supplementary Materials section.

The lancet. Psychiatry · 591 citationsread the source →

Two decades of psychological adjustment of donor-conceived offspring of lesbian parents: examining donor contact and type.

Research question: How stable is psychological adjustment in donor-conceived offspring of lesbian parents over 21 years, considering developmental stages, donor type and impact of donor contact? Design: Data were drawn from the US National Longitudinal Lesbian Family Study, a cohort of 70 donor-conceived offspring (71.43% heterosexual, 90.00% White) assessed across four developmental stages - childhood (age 10 years, Wave 4), adolescence (age 17, Wave 5), emerging adulthood (age 25, Wave 6) and established adulthood (ages 30-33, Wave 7). From parental reports, 34.29% had an anonymous donor, 34.29% a known donor and 31.43% an open-identity donor. At Waves 4 and 5, parents completed the Child Behavior Checklist to assess their child's psychological adjustment, while at Waves 6 and 7 the offspring assessed their psychological adjustment by completing the 120-item Achenbach Adult Self-Report. Growth curve models, stability coefficients and developmental pathway analyses explored trajectories by donor type, while a multivariate analysis examined differences by donor contact. Results: Across donor types, internalizing, externalizing and total problem behaviours showed low relative but high absolute stability, with fluctuations below clinical thresholds. Externalizing and total problem behaviours declined from childhood to adolescence, increased in emerging adulthood and stabilized in established adulthood. Donor type and contact did not significantly impact behavioural outcomes. Over 80% of offspring consistently scored within the normal range across all stages. Conclusions: Findings underscore the psychological resilience of donor-conceived offspring of lesbian parents, irrespective of donor type or contact. This challenges assumptions about donor-related effects on adjustment, highlighting the importance of family relationships. Flexible, family-centred support and consideration of evolving genetic-linking technologies are recommended for policy-makers and practitioners.

Reproductive biomedicine online · 4 citationsread the source →

Time-varying associations of pre-migration and post-migration stressors in refugees' mental health during resettlement: a longitudinal study in Australia.

Background: Understanding the time-varying association of pre-migration and post-migration stressors in refugees' mental health could help in designing tailored health promotion services at different resettlement stages and improving the efficiency of resource allocation. In this study, we explored these time-varying associations. Methods: We used data from the first four waves (October, 2013, to February, 2017) of a national refugee-based longitudinal study, the Building a New Life in Australia (BNLA) project. Post-traumatic stress disorder (PTSD) and high risk of severe mental illness (HR-SMI) were used to assess mental health. The independent variables included the number of potentially traumatic events experienced during the pre-migration process, and a range of post-migration stressors. We used logistic regression models to analyse the relative importance of variables and time-varying associations between the pre-migration potentially traumatic events, post-migration resettlement stressors, and refugees' mental health. Analyses were stratified by gender, and sociodemographic covariates included age, marital status, education level, country of birth, and weekly income. Results: 2399 participants were surveyed in Wave 1 of the BNLA project in 2013-14, of whom 2009 (83·7%) responded in Wave 2 in 2014-15, 1894 (78·9%) in Wave 3 in 2015-16, and 1929 (80·4%) in Wave 4 in 2016-17. The three most important factors associated with mental health in each wave differed for male and female refugees, but the socioeconomic stressors of loneliness and adjustment to life in Australia were consistently prominent. Positive associations between socioeconomic stressors and mental ill-health were found for both genders, with a peak at Wave 2 (adjusted odds ratio [AOR] among men, 1·60 [95% CI 1·26-2·03], p=0.0001 for PTSD; AOR 1·86 [1·35-2·55], p=0·0001 for HR-SMI; and among women, AOR 1·81 [1·27-2·57], p=0·0009 for PTSD; AOR 2·24 [1·49-3·38], p=0·0001 for HR-SMI). Associations between loneliness and mental health fluctuated, but were significant for both genders in Wave 4 (among men, AOR 1·90 [1·21-2·99], p=0·0051 for PTSD; AOR 3·70 [2·18-6·27], p<0·0001 for HR-SMI; and among women, AOR 3·65 [2·08-6·39], p<0·0001 for PTSD; AOR 3·68 [2·02-6·69], p<0·0001 for HR-SMI). The association between difficulties in adjustment to life in Australia and male refugees' mental ill-health increased continuously during the resettlement period. Interpretation: Gender-specific and time-sensitive services should be considered to improve refugees' mental health. For both genders, improved economic conditions that complement social security benefits deserve attention and are relevant throughout the resettlement process. At the later stage of resettlement, services to reduce loneliness could be carried out, and reducing stressors related to adjustment to life in the host country is especially needed for male refugees. Funding: None.

The lancet. Psychiatry · 63 citationsread the source →

Social isolation, loneliness, and all-cause mortality: A cohort study of 35,254 Chinese older adults.

Background: Few studies of social isolation, loneliness and associations with all-cause mortality in older adults have been conducted in non-Western countries. The aim of this study was to conduct such an analysis in a nationally representative sample of Chinese older adults. Methods: This study used eight waves of data from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2018 and focused on participants aged ≥60 years. A total of 21,570 people died (61.2%) over a median follow-up of 4.8 years. Social isolation, loneliness, demographic, health and lifestyle factors were measured at baseline. The primary outcome was all-cause mortality. Cox proportional hazard regression models were used to examine the associations of isolation and loneliness with all-cause mortality. Results: This study included 35,254 participants with mean age of 86.63 ± 11.39 years. Social isolation was significantly associated with an increased mortality (adjusted HR 1.22; 95% CI 1.18-1.25; p < 0.01). The association of loneliness with mortality was nonsignificant after adjustment for health indicators and low psychological well-being (HR 1.01; 95% CI 0.98-1.04; p = 0.69). However, when stratified by age, there was a significant association of loneliness with mortality among participants aged <80 years (HR 1.15; 95% CI 1.05-1.26; p < 0.01). Conclusions: Social isolation was associated with an increased all-cause mortality among the older Chinese adults. However, loneliness was associated with an increased mortality only among younger participants. Public health interventions aimed at increasing social connectedness may potentially reduce excess mortality among older adults.

Journal of the American Geriatrics Society · 50 citationsread the source →

Co-residence with children as a mediator between widowhood and loneliness in older adults.

Background: Loneliness in older adults, exacerbated by widowhood, is a significant public health concern. While widowhood can lead to changes in living arrangements, its impact on loneliness may vary across cultural contexts. In Western societies, widowhood often results in older adults living alone, which can intensify feelings of loneliness. However, in China, the cultural norm of filial piety and multigenerational households may lead to different outcomes. As few studies have explored this connection over time, this research seeks to bridge this gap using data from older Chinese adults. Methods: Using 16 years of data from the Chinese Longitudinal Healthy Longevity Survey, which covers 21,986 individuals aged 65-104 years, we conducted causal mediation analysis to test if changes in living arrangements (i.e., living alone versus with children) serve as a mediator between widowhood and loneliness. The potential variation in this mediation effect by gender and age was also evaluated. Results: Spousal loss was associated with an increase in loneliness. However, living with adult children post-loss reduced this emotional strain compared to living alone. The mediating influence of living arrangements was notably stronger for women than men and intensified with age in long term. In the short term, the mediating impact of living arrangements is significantly greater, particularly for older adults under 80 years old. Conclusion: Alterations in living arrangements play a pivotal role in mediating the effects of widowhood on loneliness among China's older adults. Encouraging co-residence with adult children post-spousal loss, especially for older women and the eldest age groups, might mitigate social isolation. These insights both deepen our theoretical understanding and suggest interventions to enhance the well-being of widowed older adults.

BMC geriatrics · 4 citationsread the source →

Mentalization based treatment for borderline personality disorder

Borderline personality disorder (BPD) is a complex and serious mental disorder characterized by a pervasive pattern of difficulties with emotion regulation and impulse control, and instability both in relationships and in selfimage 1. It represents a serious public health problem, because it is associated with suicide attempts and self harm, both of which are consistent targets of mental health services. Recurrent suicidal behaviour is reported in 69–80% of patients with BPD, and suicide rates are estimated to be up to 10% 2. BPD is a common condition that is thought to occur globally with a prevalence of 0.2–1.8% in the general population 3. Higher prevalence rates are found in clinical populations. Moran et al 4 found a prevalence rate of 4–6% among primary care attenders, suggesting that people with BPD are more likely to visit their general practitioner. Chanen et al 5 reported a prevalence rate of 11% in adolescent outpatients and 49% in adolescent inpatients. The highest prevalence has been found in people requiring the most intensive level of care, with a rate of 60–80% among patients in forensic services 6–7. The high prevalence and increased suicide rate in patients with BPD make an unassailable argument that effective treatment needs to be developed and that treatment has to be widely available. Whilst a number of treatments for BPD have been shown to be moderately effective in randomized controlled trials, it remains of considerable concern that most of them require extensive training, making them unavailable to most patients. Mentalization based treatment (MBT) was developed with this in mind. It requires relatively little additional training on top of general mental health training, and has been implemented in research studies by community mental health professionals, primarily nurses, with limited training given modest levels of supervision. The term mentalization grew out of the Ecole Psychosomatique de Paris and to some extent was operationalized by developmental researchers investigating theory of mind 8. It was first used by Fonagy in 1989 9 in a broader way and has since been developed in relation to understanding a number of mental disorders. Mentalization, or better mentalizing, is the process by which we make sense of each other and ourselves, implicitly and explicitly, in terms of subjective states and mental processes. It is a profoundly social construct in the sense that we are attentive to the mental states of those we are with, physically or psychologically. Given the generality of this definition, most mental disorders will inevitably involve some difficulties with mentalization. In fact, we can conceive of most mental disorder as the mind misinterpreting its own experience of itself, thus ultimately a disorder of mentalization. However, the key issue is whether the dysfunction is core to the disorder and/or a focus on mentalization is heuristically valid, i.e. provides an appropriate domain for therapeutic intervention. While mentalizing theory is being applied to a number of disorders (e.g., posttraumatic stress disorder 10, eating disorders 11 and depression 12), in a number of contexts (e.g., inpatient, partial hospital, and outpatient facilities), and in different groups of patients (e.g., adolescents, families, substance abusers), the treatment method is most clearly organized as a therapy for BPD 13. It is only in this condition that clear empirical support with randomized controlled trials 14–15 is available. In BPD, a fragile mentalizing capacity vulnerable to social and interpersonal interaction is considered a core feature of the disorder. If a treatment is to be successful, it must either have mentalization as its focus or at the very least stimulate development of mentalizing as an epiphenomenon. The failure of adult mental processing in borderline states had been apparent to most clinicians, but none had identified the primary difficulty as a loss of mentalizing arising from early development. The simple basic suggestion we made was that representing self and others as thinking, believing, wishing or desiring did not arrive at age 4 as a consequence of maturation, but rather was a developmental achievement that was profoundly rooted in the quality of early object relations. Its predictable vulnerability to disappearance under stress in borderline conditions was seen as an appropriate focus for psychodynamically oriented psychological intervention, even though concerns had been expressed over many decades about the use of psychodynamic therapy in the treatment of BPD. These began as long ago as 1938, when an American psychoanalyst, Adolph Stern, identified a group of patients, now considered to have had BPD, who did not respond to classical psychoanalytic treatment 16. He later described modifications of psychotherapy for his borderline group that remain relevant today 17. Mentalizing theory is rooted in Bowlby's attachment theory and its elaboration by contemporary developmental psychologists, whilst paying attention to constitutional vulnerabilities. There is suggestive evidence that borderline patients have a history of disorganized attachment, which leads to problems in affect regulation, attention and self control 18–19. It is our suggestion that these problems are mediated through a failure to develop a robust mentalizing capacity. Our understanding of others critically depends on whether as infants our own mental states were adequately understood by caring, attentive, non-threatening adults. The most important cause of disruption in mentalizing is psychological trauma early or late in childhood, which undermines the capacity to think about mental states or the ability to give narrative accounts of one's past relationships. Building on the accumulating evidence from developmental psychopathology, the mentalization theory of BPD first suggests that individuals are constitutionally vulnerable and/or exposed to psychological trauma; second, that both these factors can undermine the development of social/cognitive capacities necessary for mentalization via neglect in early relationships 20, especially where the contingency between their emotional experience and the caregiver's mirroring is non-congruent 21; third, that this results in an hypersensitive attachment system within interpersonal contexts; and fourth, that this leads to the development of an enfeebled ability to represent affect and effortfully control attentional capacity 22. Given the known continuity of attachment styles over time, residues of attachment problems of childhood might be expected to be apparent in adulthood. The adult attachment literature in relation to BPD has been reviewed by Levy 23. While the relationship between BPD diagnosis and a specific attachment category is not obvious, there is little doubt that BPD is strongly associated with insecure attachment (only 6–8% of BPD patients are coded as secure). It appears that early attachment insecurity is a relatively stable characteristic of BPD patients, particularly in conjunction with subsequent negative life events 24. The focus in treatment of BPD needs to be on stabilizing the sense of self and helping the patient maintain an optimal level of arousal in the context of a well-managed, i.e. not too intense and yet not too detached, attachment relationship between patient and therapist. The patient with BPD is exquisitely sensitive to all interpersonal interactions. So, the therapist needs to be aware that therapy, an interpersonal interaction, inevitably will provoke anxiety related to loss of a sense of self and that the ensuing emotional experiences will rapidly threaten to overwhelm the patient's mental capacities, leading to escalating emotions and inability to accurately understand others’ motives. Psychiatrists and other mental health professionals also need to be aware of this sensitivity if they are to avoid iatrogenic interactions with patients with BPD. Inpatient hospital admission, for example, is an intense emotional experience for all patients and, unless carefully managed, will make patients with BPD worse by overstimulating their attachment processes. This overstimulation in treatment may account for the poor long-term outcomes of patients with BPD when unmodified intensive treatments were offered (25). Patients with BPD have a vulnerability in regulating emotional responses and generating effective strategies for controlling their thoughts and feelings, which challenges their capacity for thinking about their own actions in terms of subtle understandings of their thoughts and feelings. They slip into what superficially could be described as a kind of mindless state, both in relation to others and to themselves. Of course, the story turns out to be more complicated than this, because these incapacities, palpable at certain times, are not always evident. But, at moments of emotional distress, particularly distress triggered by actual or threatened loss, the capacity for mentalization is most likely to apparently evaporate. The question is how this understanding and the clinical observations can usefully be translated into a therapeutic approach that could be helpful given the prevalence and severity of this clinical problem within a public healthcare system. To this end, we defined some core underpinning techniques to be used in the context of group and individual therapy and labeled them MBT 13–26. Only three important aspects of treatment will be considered here, namely the aim of interventions, the therapeutic stance, and mentalizing the transference. The initial task in MBT is to stabilize emotional expression, because without improved control of affect there can be no serious consideration of internal representations. Although the converse is also true, identification and expression of affect are targeted first because they represent an immediate threat to continuity of therapy as well as potentially to the patient's life. Uncontrolled affect leads to impulsivity, and only once this affect is under control is it possible to focus on internal representations and to strengthen the patient's sense of self. The aim and the actual outcome of an intervention are more important in MBT than the type of intervention itself. The primary aim of any intervention has to be to reinstate mentalizing when it is lost or to help to maintain it in circumstances when it might be lost or is being lost. Any intervention that succeeds in these aims may be used in MBT. As a result of this, MBT takes a more permissive approach to interventions than most other therapies, giving it a plurality in terms of technique which might account for its popularity and appeal to practitioners from different schools as well as the limited amount of training required before practitioners begin using it in their everyday practice. We do not ask that practitioners learn a new model of therapy from the beginning, but that they modify their current practice focussing on mentalizing rather than behaviours, cognitions, or insight. We do, however, ask that they undertake to develop a particular therapeutic stance and implement a series of steps to try to engage the patient in a process of mentalizing, firstly using some generic psychotherapy techniques such as empathy, support and clarification, and then moving on to other interventions specifically designed to “stress” the attachment relationship within controlled conditions, which includes a focus on the patienttherapist relationship through “mentalizing the transference”. The therapist's mentalizing therapeutic stance should include: a) humility deriving from a sense of “notknowing”; b) patience in taking time to identify differences in perspectives; c) legitimizing and accepting different perspectives; d) actively questioning the patient about his/her experience — asking for detailed descriptions of experience (“what questions”) rather than explanations (“why questions”); e) careful eschewing of the need to understand what makes no sense (i.e., saying explicitly that something is unclear). An important component of this stance is monitoring one's own mentalizing failures as a therapist. In this context, it is important to be aware that the therapist is constantly at risk of losing his/her capacity to mentalize in the face of a nonmentalizing patient. Consequently, we consider therapists’ occasional enactments as an acceptable concomitant of the therapeutic alliance, something that simply has to be owned up to. As with other instances of breaks in mentalizing, such incidents require that the process is “rewound and the incident explored”. Hence, in this collaborative patient-therapist relationship, the two partners involved have a joint responsibility to understand mental processes underpinning events both within and without therapy. We caution about the use of transference interpretation in the treatment of BPD because it assumes a level of mentalizing capacity of the patient that he/she often does not possess. This may have led to the suggestion that we “specifically eschew transference interpretation” (27). We do not. In fact we specifically employ transference interpretation, give indicators about when it can be used and carefully define six essential components. But equally we caution practitioners firstly about the commonly stated aim of transference interpretation, namely to provide insight, and secondly about genetic aspects, such as linking current experience to the past, because of their potential iatrogenic effects. Our first step is the validation of the transference feeling, that is establishing the patient's perspective. Of course this is not the same as agreeing with the patient, but it must be evident to the patient that the therapist has at least understood his/her point of view. The danger of the genetic approach to the transference is that it might implicitly invalidate the patient's experience. The second step is exploration. The events which generated the transference feelings must be identified. The behaviours that the thoughts or feelings are tied to need to be made explicit, sometimes in painful detail. The third step is accepting enactment on the part of the therapist. Most experiences of the patient in the transference are likely to be based on reality, even if on a very partial connection to it. Mostly this means that the therapist has been drawn into the transference and acted in some way consistent with the patient's perception of him/her. It may be easy to attribute this to the patient, but this would be completely unhelpful. On the contrary, the therapist should initially explicitly acknowledge even partial enactments of the transference as inexplicable voluntary actions that he/she accepts agency for, rather than identifying them as a distortion of the patient. Drawing attention to such therapist components may be particularly significant in modeling to the patient that one can accept agency for involuntary acts and that such acts do not invalidate the general attitude which the therapist tries to convey. Only then can distortions be explored. Step four is collaboration in arriving at an interpretation. Transference interpretations must be arrived at in the same spirit of collaboration as any other form of interpretive mentalizing. The metaphor we use in training is that the therapist must imagine sitting side-by-side with the patient, not opposite. They sit side-by-side looking at the patient's thoughts and feelings, where possible both adopting the inquisitive stance. The fifth step is for the therapist to present an alternative perspective and the final step is to monitor carefully the patient's reaction as well as one's own. We suggest these steps are taken in sequence and we talk about mentalizing the transference to distinguish the process from transference interpretation, which is commonly viewed as a technique to provide insight. Mentalizing the transference is a shorthand term for encouraging patients to think about the relationship they are in at the current moment (the therapist relationship) with the aim to focus their attention on another mind, the mind of a therapist, and to assist them in the task of contrasting their own perception of themselves with how they are perceived by another, by the therapist or indeed by members of a therapeutic group. Whilst we might point to similarities in patterns of relationships in the therapy and in childhood or currently outside of the therapy, the aim of this is not to provide the patients with an explanation (insight) that they might be able to use to control their behaviour pattern, but far more simply to highlight one other puzzling phenomenon that requires thought and contemplation, part of our general therapeutic stance aimed to facilitate the recovery of mentalization which we see as the overall aim of treatment. Our initial study of MBT 14 compared its effectiveness in the context of a partial hospital program with routine general psychiatric care for patients with BPD. Treatment took place within a routine clinical service and was implemented by mental health professionals without full psychotherapy training who were offered expert supervision. Results showed that patients in the partial hospital program showed a statistically significant decrease on all measures, in contrast with the control group, which showed limited change or deterioration over the same period. Improvement in depressive symptoms, decrease in suicidal and self-mutilatory acts, reduced inpatient days, and better social and interpersonal function began after 6 months and continued to the end of treatment at 18 months. The 44 patients who participated in the original study were assessed at 3 month intervals after of the using the same of outcome Results that patients who had partial hospital treatment not only their but also showed a statistically significant continued on most measures, in contrast with the control group of patients who showed only limited change the same period. of continued in social and interpersonal these suggest that were an was made to health care associated with partial hospital treatment compared with treatment within general psychiatric services care of all patients who participated in the was assessed using from and service were compared 6 months to 18 months of and at differences were found between the groups or treatment. the treatment the of partial hospital treatment were by psychiatric inpatient care and reduced treatment. The for to decrease in the group was not in the control group, suggesting that partial hospital treatment for BPD is no more than general psychiatric care and leads to considerable after the of treatment. patients who participated in the partial hospital treatment have now been up after initial The primary outcome for this study was number of suicide However, in the of the limited related to social in we were to whether the social and interpersonal found at the end of months had been and whether additional in the of achievement had been made in either group. Patients in the MBT program better than those treatment as their initial at the end of their general social function many more were in or full time than the group, and only for BPD compared to of the patients in the group who were for randomized controlled of MBT in an outpatient has been patients were to or clinical representing current practice. were in both conditions all outcome Patients randomized to showed a of both and significant suicide attempts and research studies are randomized controlled trials on patients with substance use disorders and patients with eating disorders. partial study of the original partial hospital has also been by an group in the that results are within mental health services from the of the treatment. MBT may not be different from other of intervention widely by and other mental health professionals in the contexts in which individuals with BPD are being We no for the intervention. MBT represents the relatively of a of developmental processes identified in all our a) the of an intense relationship based on attempts to engage the patients in a process of understanding their mental and b) the of their feelings and that patients are able to identify themselves as thinking and in the context of and high levels of emotional In the recovery of mentalization patients their thoughts and feelings, which then makes relationships and a Although we would to have identified a particular method that makes the of this therapeutic process we make no of can likely about and personality change by this and our of The of research is to identify effective and for generating change in this group.

World Psychiatry · editorial or comment · 663 citationsread the source →

The impact of end-stage kidney disease (ESKD) on close persons: a literature review

Kidney disease is defined as end-stage when a patient's glomerular filtration rate has fallen to <15 ml/min/ 1.73 m2 [1]. Mortality associated with end-stage kidney disease (ESKD) is high [2]. The incidence of treated ESKD is rising in the western world, with a corresponding increase in the incidence of diabetes and cardiovascular disease, especially in ethnic minority groups. Survival on dialysis has been shown to be poorer in the older age group, especially in patients with increased comorbidity and in those whose functional status at the start of dialysis is poor [3]. Whilst renal transplant rates vary between different countries [4], the liberalization in the acceptance of older people into renal replacement therapy (RRT) programmes, together with changes in population demographics and the fact that kidney transplantation is less suitable for this group of older patients, means that dialysis may be the only treatment option available for an increasing number of patients aged 65 years and over [5]. Recent health policy changes in the OECD countries [6,7] acknowledge that end of life care may be more appropriate for some of these people, and maximum conservative management programmes (where residual renal function is supported, haemoglobin levels maintained and symptoms relieved) have been introduced into many renal units, particularly in the United Kingdom [6]. The onset of ESKD and subsequent recommendation of dialysis as a treatment option involves a change in lifestyle for both patients and close persons [8]. Even before end-stage disease is reached, as renal function deteriorates, patients frequently require additional support, and it is often family members who provide this [9]. In the UK it is estimated that 9 out of 10 carers of patients with either physical or neurological disabilities will be close relatives. In particular when home haemodialysis is undertaken, family members have been involved in supporting patients [10,11]. Studies have shown that good family support is associated with successful adaptation to dialysis and compliance with dietary restrictions [12,13]. Conversely, one of the main factors associated with patients discontinuing dialysis is patients’ perception that they have become a ‘burden’ to close family members [14]. There is therefore a need for health professionals to be aware of the important contribution that close persons make to the care of renal patients, to communicate effectively with them and to provide bereavement support for this group when appropriate [15]. The literature on close persons of patients with renal disease has identified two main areas of impact. Firstly, both haemodialysis and peritoneal dialysis may have a disruptive influence on family members’ social lives [16] and the structure of the week may be geared towards dialysis sessions. Secondly, some patients become frail and lose functional independence, leaving family members to provide greater physical support. Family members may have health and social care needs of their own that need to be addressed [16,17]. Qyinan [18] reported that close persons commonly felt overwhelmed and stressed, although this review was limited to an evidence base of four articles and considered home dialysis only. Campbell [19] used findings from the general carer literature to illustrate demands of ageing partners with ESKD. In other chronic illnesses such as stroke [20] or in palliative care for cancer and mental health [21], interventions aimed at providing family members with training to support patients with their rehabilitation, or to address unmet needs as a result of the patient's illness, have been developed and evaluated. Results have been mixed. In the case of stroke, carers in the intervention group experienced less depression and anxiety and better quality of life [20], whilst in the palliative care study, no statistically significant differences were found between the intervention and control group on carers’ psychological outcomes [21]. However, before such interventions can be developed in ESKD, it is important to understand better the emotional and physical needs of close persons. This review aims to identify all studies involving close persons caring for ESKD patients, to describe the main findings and critique the methodology. Specific attention has been paid to (a) studies exploring the impact of ESKD on close persons, in particular for those close persons where the patients are either withdrawing from dialysis or being provided with end of life care and (b) studies looking at the provision of health care for close persons. A literature search for relevant articles was conducted in five databases: Medline (1950–2006), Embase (1991–2006), CINAHL (1982–2006), PsycINFO (1970–2006) and AMED (1985–2006), employing the following key words: carers, caregivers, end-stage kidney disease, end-stage renal disease, haemodialysis, peritoneal dialysis and renal replacement therapy. These keywords were used both in word search options and exploded as thesaurus terms to obtain the maximum number of articles. The abstracts for each article were read to check for inclusion into the main review, using the following criteria: Published in peer-reviewed journals. Research studies with an introduction, a methodology and results section and a conclusion. Involve close persons, defined as either a family member or the person identified by the patient as an informal carer. By an informal carer, we mean a person who provides the majority of a patient's physical and emotional care needs and who is neither a volunteer nor in the employment of statutory services. Use a sample of close persons caring for adult ESKD patients (over 18 years). Non-English language articles were considered if the English translation of the abstract met the above criteria. Using these criteria, 334 articles were identified from the five databases (139 in Medline, 121 in Embase, 80 in CINAHL, 8 in AMED and 34 in PsycINFO). J.L. went through the abstracts of each of the 382 articles, of which 37 initially met the inclusion criteria. One was later excluded on closer inspection, as it was specifically a validation study of a fatigue severity scale. Of the remaining 36 studies, 16 exclusively looked at family members, 12 specifically at the patient-family dyad and 3 at the family-health professional dyad. Whilst the latter two types of studies did not concentrate solely on family concerns, we decided to include them in the analysis, because these findings further contribute to the limited number of studies in this field. Thirty-six studies were included in the review. Both J.L. and G.S. first went through the remaining 36 studies independently and extracted the following information for each study: the number of carers in the study sample, the RRT population they were caring for, authors’ definition of a carer, demographic details of the sample, patients’ dialysis history, caring history, study design, outcome measures used and main findings. J.L. and G.S. then met together to discuss these findings and obtain an initial consensus before meeting with A.B. and L.J. to obtain a final consensus. We undertook an exploration of the aims of these studies, their study design, the sample of participants and the outcome measures highlighted in the quantitative studies. The three main themes explored were (a) the impact of caring for a patient with ESKD on dialysis on close persons, in particular quality of life, psychological morbidity, close person responsibilities—which authors often referred to as ‘burden’ or ‘carer burden’—and their life situation; (b) the coping strategies employed by these close persons and (c) factors that influence psychological morbidity. No studies of health provision for close persons of patients with ESKD were identified. Four studies looking at end of life issues explored the following themes for close persons: (a) their perceptions of patients’ terminal symptoms; (b) their reasons for why patients decided to stop dialysis; (c) the long-term impact of patient death following dialysis cessation and (d) their perceptions of advance directives. End of life care may be provided by the renal multi-disciplinary team alone, or it may involve referral for specialist palliative care advice. Such advice is likely to include symptom control, attention to spiritual and psychological issues for patients and, where possible, involvement of their families in decision-making. Whilst most studies were interested in the direct impact on close persons only, one triangulated close person data with patient data. The majority of studies reviewed used a cross-sectional design; there was only one longitudinal study. Whilst most were quantitative (24/36), there were some qualitative studies (11/36) and one used a mixed methods approach. The total sample was predominantly female, with mean ages ranging from 41 to 68 years (analysis possible in only 18 studies). Sample sizes also tended to be small, with a median sample of 55 participants for the quantitative and 15 participants for the qualitative studies. Most of the sample was recruited in studies where associated patients were undergoing haemodialysis or peritoneal dialysis. Three studies also involved kidney transplant patients. Only five studies looked at close persons dealing with end of life issues or with patients withdrawing from dialysis. Many studies did not focus on close persons in their potential role as ‘informal carers’. Thirteen studies actively sought close persons who also considered themselves to be informal carers, of which eight provided full definitions of what they meant by this term. All studies included spouses as part of their sample, of which eight specifically concentrated on this group alone. Adult children were included in seven of these studies and parents in five. A wide variety of outcome measures were used to rate health-related quality of life, anxiety, depression, coping strategies and patient disease severity. Some studies used standardized outcome measures; others used simple self-rated tools. The most commonly used standardized measures were the Zarit Burden Interview [22] to evaluate the sense of carer responsibility (3/8), the Beck Depression Scale [23] to evaluate depression (2/5), SF-36 [24] to evaluate health-related quality of life (3/8), Jalowiec Coping Scale [25] to evaluate close persons’ use of coping strategies (3/3) and End-Stage Renal Disease Severity Index [26] to evaluate patients’ disease severity (2/4). A breakdown of the country of origin for each study showed that over half originated from either the USA (11/36) or Canada (7/36), with five originating from Australia and only seven from the European Union, of which only one was conducted in the UK. The remaining six studies came from the following countries: Japan (2/36), Brazil (2/36), China (1/36) and Turkey (1/36). The 36 studies have shown mixed results. They have mainly explored the following areas associated with caring for an ESKD patient: the impact on close persons and their social life and the factors affecting close persons’ psychological health. There have been very few studies looking at palliative care issues and these have primarily concentrated on dealing with end of life issues rather than the provision of supportive care in the pre-terminal phase. In only one study, close persons rated their quality of life as excellent and reported few pressures resulting from their carer responsibilities [27], whilst in all others, ESKD and dialysis were shown to increase the close person's sense of responsibility and lead to a poorer quality of life when compared with age-matched controls [28]. Close persons found living with an ESKD patient on dialysis stressful [29] and experienced increased fatigue [30]. The dominating effect of caring for an ESKD patient often led close persons to neglect their own health. For those who took time to have a break from their carer responsibilities, there were health benefits [31]. Other issues that close persons reported included isolation through the loss of social activity [30–36], life restrictions [36–38], increased workload, negative economic consequences [39,40], changed relationship with the patient [30,34] and sexual problems for spouses [41]. Impact on family life (quantitative and mixed methods studies) CAPD = Continuous Ambulatory Peritoneal Dialysis; CBI = Caregivers Burden Interview; FES = Family Environment Scale; HD = Haemodialysis; IIRS = Illness Intrusiveness Ratings Scale; MAES = Marital Attitudes Evaluation Scale; NGQ = Norris & Groves Questionnaire; PAF = Physicians’ Assessment Form; PAIS = Psychosocial Adjustment to Illness Scale; SF-36 = Short-Form 36; SwQoL = Swedish Health-Related Quality of Life Survey; VAS = Visual Analogue Scale; ZBI = Zarit Burden Interview. Impact on family life (quantitative and mixed methods studies) CAPD = Continuous Ambulatory Peritoneal Dialysis; CBI = Caregivers Burden Interview; FES = Family Environment Scale; HD = Haemodialysis; IIRS = Illness Intrusiveness Ratings Scale; MAES = Marital Attitudes Evaluation Scale; NGQ = Norris & Groves Questionnaire; PAF = Physicians’ Assessment Form; PAIS = Psychosocial Adjustment to Illness Scale; SF-36 = Short-Form 36; SwQoL = Swedish Health-Related Quality of Life Survey; VAS = Visual Analogue Scale; ZBI = Zarit Burden Interview. Impact on family life (qualitative studies) CAPD = continuous ambulatory peritoneal dialysis; HD = haemodialysis; PD = peritoneal dialysis. Impact on family life (qualitative studies) CAPD = continuous ambulatory peritoneal dialysis; HD = haemodialysis; PD = peritoneal dialysis. The treatment modality may also have an impact on family members. Studies have highlighted that spouses of transplant patients were more assertive, self-sufficient and able to handle the physical, social and existential aspects of the illness better than dialysis spouses [33,42]. Despite these pressures, close persons recognized that they play a positive role in promoting patients’ well-being [11,43]. They recognized that health care professionals were important in providing support to discuss their problems [39] and would like to have more information about the care being provided to patients [44]. However, they also reported poor communication with professionals, felt that their needs were not always addressed [30,39,45] and felt themselves uneducated and poorly equipped to deal with the regimented lifestyle associated with the dialysis regimen [14]. Whilst some studies have shown that close persons display few signs of psychological distress [40,46–49], others have identified the following: Caring and psychological health ABS = Affect Balance Scale; BDI = Beck Depression Inventory; BI = Barthel Index; CAPD = Continuous Ambulatory Peritoneal Dialysis; CAS = Clinical Anxiety Scale; CBI = Caregivers Burden Interview; CBS = Caregiver Burden Scale; CES-D = Center for Epidemiologic Studies Depression Scale; CID = Cognitive Index of Depression; DAS = Adjustment Scale; = = Anxiety and Scale; = Questionnaire; = Depression Questionnaire; = Questionnaire; = End-Stage Renal Disease Severity Index; = End-Stage Renal Disease Severity = Family Questionnaire; = Scale; = = Index; HD = haemodialysis; = Scale; = Impact on Family Scale; = Jalowiec Coping Scale; = Scale; = of control of = Marital Adjustment = Marital Questionnaire; = Scale of = Psychosocial Adjustment to Illness PD = peritoneal dialysis; = Scale; = for and Family Scale; = Quality of Life Index; = Scale; = Inventory; SF-36 = Short-Form 36; = = Anxiety Inventory; = with Life Scale; = ZBI = Zarit Burden Interview. Caring and psychological health ABS = Affect Balance Scale; BDI = Beck Depression Inventory; BI = Barthel Index; CAPD = Continuous Ambulatory Peritoneal Dialysis; CAS = Clinical Anxiety Scale; CBI = Caregivers Burden Interview; CBS = Caregiver Burden Scale; CES-D = Center for Epidemiologic Studies Depression Scale; CID = Cognitive Index of Depression; DAS = Adjustment Scale; = = Anxiety and Scale; = Questionnaire; = Depression Questionnaire; = Questionnaire; = End-Stage Renal Disease Severity Index; = End-Stage Renal Disease Severity = Family Questionnaire; = Scale; = = Index; HD = haemodialysis; = Scale; = Impact on Family Scale; = Jalowiec Coping Scale; = Scale; = of control of = Marital Adjustment = Marital Questionnaire; = Scale of = Psychosocial Adjustment to Illness PD = peritoneal dialysis; = Scale; = for and Family Scale; = Quality of Life Index; = Scale; = Inventory; SF-36 = Short-Form 36; = = Anxiety Inventory; = with Life Scale; = ZBI = Zarit Burden Interview. A negative between close persons’ psychological health and their sense of carer responsibility their use of coping strategies strategies that the symptoms of the of the the close person's age and the social and changes as a result of ESKD A positive between good mental health and the following a of of dialysis the of dialysis patients are on of social support and sense of carer responsibility The sense of carer responsibilities are if patients are in of living have less or comorbidity This was further in studies in patients home haemodialysis or transplant where close persons not anxiety or depression felt less by their carer responsibility and a quality of life to the age-matched population were found between levels of responsibility and other outcomes such as quality of life and The use of coping was found to have a negative with a positive with the number of years on dialysis Close persons were more likely to have negative towards patients if they no of the dialysis and a high of involvement with the caring whilst living in a We identified five studies that explored end of life only one specifically on close persons. This study the long-term impact of death on families when dialysis was found that most families felt that patients a good death as at and with close people and most family members showed only levels of However, carers and those with levels of caring responsibility for the did End of life care HD = End of life care HD = The remaining four studies on patient outcomes such as reasons for withdrawing from dialysis the quality of death the of close persons in ESKD patients’ to and care and use of advance as a in advance by patients, which the of treatment to be by health care a patient is to provide to that person's of These studies found that close persons that whilst most patients a many patients were to be in and from fatigue care family members in that patients’ were and most recognized the of living which they felt were health care professional Close persons were poorly for caring for a dialysis and patients did not to be a on their families [14]. They were also poor at both patients’ and for or dialysis No studies were identified for carers of patients with supportive care those on maximum conservative management The main of most studies included in this review is the of and of the demographic over half of the studies demographic details of close persons’ ages and or details of their relationship to patients of other relevant demographic such as employment status or social is and only seven studies the time that close persons as Whilst all studies the of dialysis half reported the of time a patient has been on with very few patients’ functional although carer studies in other that this has an impact on carers’ quality of life In only 18 9 qualitative and mixed methods study details of their sample of the quantitative studies included in the used cross-sectional and were predominantly Such studies are in exploring between are limited as they not to be only five studies provide the full details of sample it is therefore not possible to rates or the sample The sample sizes were with a median of 55 and details of were reported in only one study. the of the used to the different outcomes it to between the different studies. We identified that most studies poor of their methods and a of of their data Most used of family members with five studies using only one details of their studies with their studies with their one a of their their approach. One study no details of their the studies were poorly that the was and authors were as to to use qualitative data with the and of the qualitative data demographic of data and poor use of supporting This study reviewed the literature exploring the of close persons of patients with ESKD, from which can be the quality of and for the of in this Firstly, studies exploring end of life issues are with only four identified. these four studies are they that health are the time for informal carers to discuss patients’ about end of life care and, long-term distress of close persons resulting from the patients’ However, about such end of life issues close persons, and we studies in this Secondly, definitions of close persons were there were some differences identified between the different groups. the literature the that most close persons are to patients, the in to patients who were and those with family and relationship were not not all close persons to on the role of the informal carer, and the of this role can be a as illness review did not identify differences between informal carers and family carers in the outcome measures used included both the of differences may in their with ‘informal carers’ a more members’ may be as being more this needs further issues that need to be addressed the use of methodology were identified in the Most quantitative studies were and with no intervention studies being identified. Studies of demographic details and rates and all were cross-sectional with sample sizes that used standardized Whilst the use of standardized measures the of the the findings from cross-sectional studies are limited in that they can only between We the use of longitudinal methods in that would that between key be explored in more This would also into the long-term of close persons. In those studies using qualitative most used with poor and of demographic and social and Many authors used the ‘burden’ or ‘carer such terms may influence of the relationship between close person and was not they were by close persons to use the ‘burden’ or it was a by the authors to describe the responsibilities of Such and the of study findings the half of the studies originated from either the USA (11/36) or Canada This it to the results of these studies their to in the of health care provision in other there is evidence that the psychological health of close persons them to to care which in can the mental health of patients, we to identify studies in review that looked specifically at health close persons of patients with ESKD. review has identified in the literature that need to be is therefore to the relationship between health and close persons in to We would like to acknowledge for this review and for support in this of

Clinical Kidney Journal · editorial or comment · 83 citationsread the source →

Cross-national differences in grip strength among 50+ year-old Europeans: results from the SHARE study.

Grip strength (GS) has an age- and gender-dependent decline with advancing age. One study comparing GS among extremely old show a North-South gradient with lowest GS in Italy compared to France (intermediary) and Denmark (highest) even after adjusting for confounders. As GS is associated with higher rates of functional decline and mortality, and thus may be used as a health indicator, it is of interest to examine whether the results on extremely old can be reproduced in a large-scale European survey. GS was measured in a cross-sectional population-based sample of 27,456 individuals aged 50+ in 11 European countries included in the SHARE survey. We made a cross-country comparison of the age trajectory of GS in both genders. Northern-continental European countries had higher GS than southern European countries even when stratifying by age and gender and controlling for height, weight, education, health and socioeconomic status. The relative excess was found to be 11% and the absolute difference 5.0 kg for 50- to 54-year-old men, increasing to 28% and 6.9 kg among 80+ year-old men. The corresponding figures for women were 16% and 4.3 kg, and 21% and 3.5 kg, respectively. Southern European countries have lower GS in the age range 50+ year. Gene-environment interactions may explain country-specific differences. The use of GS in cross-national surveys should control not only for age and gender, but also for nationality.

European journal of ageing · 86 citationsread the source →

Seroprevalence of cytomegalovirus infection in the United States, 1988-1994.

Background: Cytomegalovirus (CMV) is a leading cause of congenital illness and disability, including hearing loss and mental retardation. However, there are no nationwide estimates of CMV seroprevalence among pregnant women or the overall population of the United States. Methods: To determine CMV prevalence in a representative sample of the US population, we tested serum samples for CMV-specific immunoglobulin G from participants aged > or =6 years (n=21,639) in the third National Health and Nutrition Examination Survey (1988-1994). Results: The prevalence of CMV infection was 58.9% in individuals > or =6 years old. CMV seroprevalence increased gradually with age, from 36.3% in 6-11-year-olds to 90.8% in those aged > or =80 years. CMV seroprevalence differed by race and/or ethnicity as follows: 51.2% in non-Hispanic white persons, 75.8% in non-Hispanic black persons, and 81.7% in Mexican Americans. Racial and/or ethnic differences in CMV seroprevalence persisted when controlling for household income level, education, marital status, area of residence, census region, family size, country of birth, and type of medical insurance. Among women, racial and/or ethnic differences were especially significant; between ages 10-14 years and 20-24 years, seroprevalence increased 38% for non-Hispanic black persons, 7% for non-Hispanic white persons, and <1% for Mexican Americans. Conclusions: On the basis of these results, we estimate that each year in the United States approximately 340,000 non-Hispanic white persons, 130,000 non-Hispanic black persons, and 50,000 Mexican American women of childbearing age experience a primary CMV infection. Given the number of women at risk and the significance of congenital disease, development of programs for the prevention of CMV infection, such as vaccination or education, is of considerable public health importance.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 658 citationsread the source →

Sexual difficulties and help-seeking among mature adults in Australia: results from the Global Study of Sexual Attitudes and Behaviours.

Background: The Global Study of Sexual Attitudes and Behaviours was a survey of 27 500 men and women in 29 countries. Here we report the sexual activity, the prevalence of sexual difficulties and related help-seeking behaviour among participants in Australia. Methods: A telephone survey was conducted in Australia in 2001-2002, with interviews based on a standardised questionnaire. A total of 1500 individuals (750 men and 750 women) aged 40 to 80 years completed the survey. The questionnaire covered demographic information, overall health, and sexual behaviours, attitudes and beliefs. Results: Overall, 83% of men and 74% of women had engaged in sexual intercourse during the 12 months preceding the interview, and 38% of all men and 29% of all women engaged in sexual intercourse more than once a week. Early ejaculation (23%), erectile difficulties (21%) and a lack of sexual interest (18%) were the most common male sexual difficulties. The most frequently reported female sexual difficulties were: lack of sexual interest (33%), lubrication difficulties (26%) and an inability to reach orgasm (25%). Older age was a significant predictor of male erectile difficulties and of lubrication difficulties in women. Only a minority of men and women had sought help for their sexual difficulty(ies) from a health professional. Conclusions: Many middle-aged and older adults in Australia report continued sexual interest and sexual activity. Several sexual difficulties are highly prevalent in this population, but those experiencing these difficulties rarely seek medical help. This may be because they do not perceive such difficulties as serious or sufficiently upsetting.

Sexual health · 51 citationsread the source →

Cumulative childhood stress and autoimmune diseases in adults.

Objective: To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. Methods: Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0-8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). Results: Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p < .05). Compared with persons with no ACEs, persons with >or=2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p < .05). Conclusions: Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses.

Psychosomatic medicine · 438 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 →

Survey of the rural allied health workforce in New South Wales to inform recruitment and retention.

Objective: To investigate the demographics, employment, education and factors affecting recruitment and retention of New South Wales (NSW) rural allied health professionals. Design: Descriptive study, cross-sectional survey. Setting: Regional, rural and remote areas of NSW, Australia. Participants: The sample includes 1879 respondents from more than 21 different allied health occupations. Main outcomes measures: Variables included gender, age, marital status, employment sector, hours worked, community size, highest qualification, rural origin and continuing education, as well as others. Certain variables were compared for profession and gender. Results: Women made up 70% of respondents, with a mean age of 42 years. Men were older, with more experience. Sixty per cent were of rural origin and 74% partnered, most with their partner also working. Eighty-four per cent worked in centres of 10,000 or more people. The public sector accounted for 46% of positions and the private sector 40%. Eleven per cent worked across multiple sectors and 18% were self-employed. Two-thirds worked 35 hours or more per week, although only 49% were employed full-time. Job satisfaction was high but 56% intended leaving within 10 years, 28% to retire. Over 90% of respondents qualified in Australia and more than 80% held a degree or higher qualification. Almost half were dissatisfied with access to continuing education. Conclusions: The NSW rural allied health workforce is strongly feminised, mature and experienced. Recruitment should target rural high school students and promote positive aspects of rural practice, such as diversity and autonomy. Retention strategies should include flexible employment options and career development opportunities.

The Australian journal of rural health · 50 citationsread the source →

Health-related quality of life and low back pain of patients surgically treated for scoliosis after 21 years or more of follow-up: comparison among nonidiopathic scoliosis, idiopathic scoliosis, and healthy subjects.

Study design: A case-control study. Objective: To compare health-related quality of life and low back pain of healthy subjects with those of patients with nonidiopathic scoliosis (non-IS) and idiopathic scoliosis (IS) 21 years or more after surgery. Summary of background data: There have been a very small number of reports on long-term results of surgery for non-IS. There have not been any reports that compare non-IS, IS, and healthy subjects. Methods: The subjects with scoliosis were 602 patients who had undergone surgery between 1968 and 1988. The Scoliosis Research Society Patient Questionnaire (SRS-22), Roland-Morris Disability Questionnaire (RDQ), and our institution's original questionnaire were used for evaluating long-term clinical outcomes. The 136 respondents consisted of 56 patients with non-IS (non-IS group) and 80 patients with IS (IS group). The control group (CTR group) consisted of 80 healthy volunteers who were age- and body mass index-matched to the scoliosis groups. Results: In the SRS-22, the 3 groups had no significant differences in pain and mental health. For function and self-image, the non-IS group and the IS group had a significantly lower score than the CTR group. In the RDQ, the non-IS group had significantly more severe low back pain than the CTR group. There was no significant difference in low back pain between the non-IS group and IS group or between the IS group and CTR group. The non-IS group had a significantly lower marriage rate than the IS and CTR groups. Conclusion: The patients with non-IS and IS had similar health-related quality of life and low back pain. The patients with non-IS were found to have lower function and self-image in the SRS-22 questionnaire and more severe low back pain in the RDQ than healthy subjects. The patients with non-IS had a significantly lower marriage rate than the other 2 groups.

Spine · 22 citationsread the source →

Positive mental health: is there a cross‐cultural definition?

The great epidemiological studies of the past half century have focused upon who was mentally ill and not who was well. Mental illness, after all, is a condition that can be defined reliably, and its limits are relatively clear. Until recently, only the Sterling County Studies by A. Leighton 1 came close to defining positive mental health operationally. In addition, it has been argued that achieving above average mental or physical health is not the province of medicine, but of education. Early in the past century, internists began studying physiology at high altitude and devise measures of positive physical health for athletes, pilots, and finally astronauts. In 1929–30, at the University of California at Berkeley, the Institute of Human Development was founded by H. Jones, N. Bayley and J. McFarlane 2,3. Originally created to study healthy child development, the Institute was to provide a seminal influence on E. Erikson's model of healthy adult development. In the late 1930s, A. Bock, an internist trained in high altitude physiology and interested in positive physical health, began the Study of Adult Development at the Harvard University 4,5. This was designed as an interdisciplinary study of both mental and physical health. Like physical fitness, positive mental health is too important to be ignored, but its definition is not easy. Several precautions are necessary. First, in defining mental health, cross-cultural differences must be kept in mind. My own efforts to define mental health may appear parochial to those from other countries. Thus, the commentaries on this paper will be particularly important. The second precaution is to keep in mind that “average” is not healthy. Community surveys always mix in the healthy with the prevalent amount of psychopathology. In the case of red blood count, or thyroid function, the middle of the bell curve is healthy. In the case of eyesight, only the upper end of the bell curve is healthy; and in the case of cholesterol and bilirubin only the low end of the curve is healthy. A third precaution is to make clear whether one is discussing trait or state. Longitudinal study is particularly important. A world-class soccer player temporarily sidelined with a sprained ankle (state) is probably healthier than a type 1 diabetic (trait) with a temporarily normal blood sugar. Finally, mental health needs to be seen in context. Sickle cell trait is unhealthy in Paris, but not in central Africa where malaria is endemic. In the 1940s, paranoid personalities made very poor submariners but excellent airplane spotters. Punctuality and competitiveness are seen as healthy in some communities, but not in others. Moreover, if mental health is “good”, what is it good for? The self or the society? For “fitting in” or for creativity? In defining mental health, biology usually trumps anthropology. Cultural anthropology teaches us that almost every form of behavior is considered healthy in some cultures, but that does not mean that the tolerated behavior is mentally healthy. Until recently, Portugal did not recognize alcoholism as an illness, but that did not reduce the contribution of alcoholism to mortality in Lisbon. The best way to enrich our understanding of what constitutes mental health is to study a variety of healthy populations from different perspectives, in different cultures and for a long period of time. This paper will contrast seven different empirical models of mental health. First, mental health can be conceptualized as above normal, as epitomized by a DSM-IV's Global Assessment of Functioning (GAF, 6) score of over 80. Second, it can be regarded as the presence of multiple human strengths rather than the absence of weaknesses. Third, it can be conceptualized as maturity. Fourth, it can be seen as the dominance of positive emotions. Fifth, it can be conceptualized as high socio-emotional intelligence. Sixth, it can be viewed as subjective well-being. Seventh, it can be conceptualized as resilience. To avoid quibbling over which traits characterize mental health, it is helpful to adopt the analogy of a decathlon champion. What constitutes a “track star”? A decathlon star must possess muscle strength, speed, endurance, grace and competitive grit, although the combinations may vary. Amongst decathlon champions, the general definition will not differ from nation to nation, or century to century. The salience of a given facet of a decathlon champion, or of mental health, may vary from culture to culture, but all facets are important. After World War II, influential works on mental health began to be published 7,8,9. Although all studies concentrated on normal populations, they still put their emphasis on not pathological rather than on above average mental health. Besides, many post-war psychiatrists continued to agree with S. Freud who had dismissed mental health as “an ideal fiction”. Then, in 1958, M. Jahoda's report to the American Joint Commission on Mental Illness and Health 10 led to a psychiatric sea change regarding the existence of mental health. She suggested that mental health includes autonomy (being in touch with one's own identity and feelings); investment in life (self-actualization and orientation toward the future); efficient problem solving (accurate perception of reality, resistance to stress, environmental mastery); and ability to love, work and play. However, at the time she published her criteria, there was still no evidence to prove that her plausible definitions were more than mere platitudes. Next, came R. Grinker's 1962 studies of “homoclites”, the first empirical study of positive mental health 11. Grinker's homoclites were physical education majors selected for normality but studied only briefly. A second more longitudinal study was the elimination process, by which out of 130 healthy jet pilots, already selected for mental health, the seven original American astronauts were selected 12. These astronauts not only enjoyed exemplary work records, but also were competent at loving. Although venturesome test pilots, they all had had very few accidents during their years of flying. They could tolerate both close interdependent association and extreme isolation. Although each of the astronauts was very different, they all would have starred in a mental health “decathlon”. An even more influential study of mental health was the Menninger Psychotherapy Project led by the psychologist L. Luborsky. He devised the Health-Sickness Rating Scale, with a scale from 0 to 100 13, based on behavior rather than pencil and paper tests. A score of 80 or above reflected positive mental health; a score of 95–100 reflected “an ideal state of complete integration, of resiliency in the face of stress, of happiness and social effectiveness”. Luborsky's scale was modified by two of the architects of DSM-III into what is now Axis V 14. In cross-cultural comparisons, investigators have confirmed the usefulness of Luborsky's measure as an international thermometer of mental health 15. The fact that psychologists have approached mental health somewhat differently from psychiatry has led to this second model, which has provided the basis for the positive psychology movement 16. Psychologists, like physiologists, look at continua (traits) rather than categories, while in medicine you either have an illness or you do not. In psychology, interventions to improve adequate intelligence or social skills are common, while in medicine to meddle with adequate thyroid function, or a healthy hematocrit or a normal mood, is only to cause trouble. In the healthy rested individual, virtually all psychopharmacological interventions will, over time, make the brain function worse. Thus, the medical goal of using medication to remove pathology is different from the psychologists’ goal of fostering positive mental health in an educative model. As early as in 1925, the psychiatrist A. Meyer was already warning of the need to stop “moralizing” about utopian mental health. Mental health, he suggested, should be studied through “conscientious and impartial study” and “constructive experimentation” 17. Subsequently, the psychologist M. Seligman stated that positive psychology will use evidence-based experimentation to study positive mental health and incorporate recent empirical advances in cognitive psychology 18. Since the late 19th century, many social scientists had mistrusted optimistic cognition, especially religious optimism, as a maladaptive “American” illusion interfering with accurate perception of reality. Nietzsche, Freud, Marx and Darwin all perceived optimism as evidence of an ingenuous cultural adolescence, not of mature mental health. However, cognitive therapists have then demonstrated that optimistic cognition can not only change behavior, but even alter brain function 19. If pessimism is the dominant cognition of the depressed, optimism appears the dominant cognition of the mentally healthy. In part, the importance of optimism to positive mental health depends upon an attributional cognitive style which asserts that the good things happening to me are my “fault”, will last forever and are pervasive, while the bad things are limited, not my fault, and unlikely to happen again 20. The psychologists C. Peterson and M. Seligman identified four components in positive mental health: talents, enablers, strengths, and outcomes. Talents are inborn, genetic and are not much affected by intervention (e.g., high IQ) 21. Enablers reflect benign social conditions, interventions, and environmental good luck (e.g., a strong family, a good school system, living in a democratic merito- cracy). Strengths are character traits (such as kindness, forgiveness, curiosity, honesty) which reflect facets of mental health that are amenable to change. Outcomes reflect dependent variables (e.g., improved social relationships and subjective well-being) which can be used to provide evidence that efforts by clinicians to enhance strengths are effective. Which strengths are most associated with mental health is open to debate. Wisdom, kindness and the capacity to love and be loved are strengths upon which few would argue. But should courage be included as a strength? And why were intelligence, perfect musical pitch and punctuality excluded? In addition, there is considerable debate within the mental health professions about whether positive mental health is a process that any insurance program should be expected to cover. Over time society will have to decide who should pay for positive mental health: the individual, the educational system, third party payers, religious organizations, or a combination of all four? Unlike other organs of the body that have evolved to stay the same or deteriorate after puberty, the human brain continues to evolve in adulthood. A ten-year-old's lungs and kidneys are more likely to reflect optimal function than are those of a sixty-year-old, but that is not true of their central nervous systems. To some extent, then, adult mental health reflects a continuing process of maturational unfolding and progressive brain myelinization into the sixth decade 22,23. Prospective studies reveal that individuals are less depressed and show greater emotional modulation at age 70 than they did at age 30 5,24. In some respects E. Erikson in 1950 anticipated Jahoda and Grinker when he provided the first model of adult lifespan development 25. All previous models had depicted deterioration after 45–50. In contrast, Erikson viewed each of his eight stages of human development as a fresh “criterion of mental health”. Subsequently, J. Loevinger provided a model of adult ego development 26 and L. Kohlberg built up a model of adult moral development 27. Implicit in all these models is the assumption that greater maturity reflects greater mental health. Arguably, the best definition of mental health that we have is W. Menninger's definition of maturity 28 as capacity for love, absence of stereotyped patterns of problem solving, realistic acceptance of the destiny imposed by one's time and place in the world, appropriate expectations and goals for oneself, and capacity for hope. In this model, maturity is not only the opposite of narcissism, but it is quite congruent with other models of mental health. To support the maturational model of mental health, the assessment of the behavior and feeling states of persons studied over a lifetime becomes necessary. Although such longitudinal studies have come to fruition only recently, all illustrate the positive association of maturity with increasing mental health 5,24,29,30,31. In order to illustrate the association between mental health and brain maturity, individuals with brain trauma, major depression, arteriosclerosis, Alzheimer's disease, alcoholism, and schizophrenia must all be excluded. Erikson conceptualized that maturity, through the evolution of adult development via life experience, produces a “widening social radius”. In Erikson's model, adult maturity is achieved over time through the mastery of the four sequential tasks of “identity”, “intimacy”, “generativity”, and “integrity”. On the basis of empirical data from Study of Adult has two more to and of the to the mastery of such tasks appears relatively of social and probably The age at which any is but the maturity of life is with mental health. is not a of of from or of to out of a is a of between the of from and the of where one's end and one's own as much from the and of important and as it does from For our relatively by age and reflect those of our rather than the of our Next, should which to and not with a with one other in an and may to a the capacity for may as and as a the is with a of the same it is and as in religious the is with a is a that is usually with or that the mastery of of this to a as as they play. are four that a into a to not a and to is almost of of the the of a clear capacity to for and the that between age and our need for and our need for and on the that the society can mean as a or to in the is achieved by a more than half the and is a of positive mental health in other The life is to a of the This of on the of the past to the The of a of the is on and of the of and its of one rather than In contrast, of the and its of and are less for not The last life is the of achieving some of and with to both one's own life and the world, and the acceptance of one's life as that had to be and by of no In our healthy adult development the same for and as for However, cross-cultural is In the 19th century, psychiatrists of like and and mental health was to and religious the century, the of cultural and in general led psychiatrists to there was any between as by and health. However, recent advances in the understanding of positive have psychiatry In the last positive to and have been years medical were about like and are also in and like and love were to be in the and in the of of education not of Then, in the H. and J. to love as rather than love as the basis for to provide to the of and even of with his of and The out that the our not only to but also to to out at and to of our own for of these a and she do but a competent her system, and she can still do but not her The of positive clear. the last have studies the of positive emotions. studies have human and in especially in the and These are and to us to and to recognize all that the of love and human In the last years like J. and have identified the and that human in the and and appear to the of the of The of in the and is most in individuals with the of social and confirmed by pencil and paper positive forgiveness, and the important positive and included in this model. great the eight selected positive all human is all about they are all and they all appear to be a of the major from the are other positive and a of for we can these while on a importance to are all about both the of and but the mental health of these two are very are for in time by like J. and psychologists like and S. while and the for the positive especially make patterns more and on time positive our for our moral and enhance our The of positive on the nervous has much in with the and via our nervous system, and via our nervous system, reduce blood and muscle studies of that of the and the which in to and the of socio-emotional intelligence reflects above average mental health in the same way that a high reflects above average emotional intelligence at the of positive mental health. In the defined socio-emotional intelligence as can that is easy. But to be with the to the at the time, for the and in the way that is not as as years a on intelligence dismissed the of such social intelligence as only in the did the modulation of more important to psychiatry than the modulation of and emotional intelligence can be defined by the accurate perception and of one's own of our that their is accurate of and to in in close relationships with capacity for toward a Over the last have been to our understanding of the of socio-emotional intelligence to positive mental health. The first is that both and experimentation have led to advances in our understanding of the of with the The second has been our but in the and even the of Over the last measures of emotional intelligence have been are now many in relationships that and more at and In the past there has also been an increasing to emotional and social for mental health, they considered for happiness and the However, if through the have regarded happiness as the psychologists and psychiatrists have to that from or love or from and or from and but reflects health. that from and or from mature or from of on and the is a to depends upon achieving positive and positive relationships 18. On the other subjective happiness can have maladaptive as as The for happiness can appear and can come and be happiness is seen in the character associated with and and with of by much American of maladaptive can to any but need like and is of such of in this the will be for The of the has always been of American with in the last have investigators like M. Seligman and E. out that a function of subjective is that it an to for and disease, high in subjective efforts to measure subjective have been quite and a investigators measure subjective as life other investigators more like work or However, the do you about life as a on a scale from to works well. environmental variables can have a is that are the most way to subjective well-being. such are by at during the for or and at each are to their subjective in order to from subjective experience, measures of measures of and by have also are of that use to The first two are social support and cognitive that we to The third of is by which our perception of and in order to reduce subjective and These mental are by the of as They can (e.g., by or (e.g., by or the need for other (e.g., by or (e.g., by They can our of the (e.g., by or the of a (e.g., by the or the (e.g., by or the associated with an (e.g., of The most pathological of includes and of reality. to life are the and maladaptive in and in with out and The third of associated with and with the of and at a more The of characterize mental health still and alter relationships and reality, but they these and as one would be by a upper in the ability not to one's self too and into are the very from which positive mental health is But these be achieved by a of Thus, the such as as the may the of and the of out as like other facets of mental health, the of healthy but longitudinal Studies from both Institute of Human Development and Study of Adult Development have the importance of the mature to mental health. as psychiatry needs to on Axis a score of psychiatry needs to best to the of less mature into more mature is in using studies to these are by the brain and to use empirical to change in the of during This paper has suggested seven models of positive mental health. As in the Study of Adult Development at Harvard an empirical of the of of these different models in a study of only was each of models by with the other but each model mental health years of the models was by social or even by a The of mental health the of interventions to What facets of mental health are and which are to As can mental illness, but do not improve healthy brain can enhance mental health only through and education. Finally, the study of positive mental health First, mental health must be defined in that are and Second, the for mental health must be and Finally, although mental health is one of important it should not be regarded as an good in must in our efforts to positive mental health while for This work was by from the Institute of Mental

World Psychiatry · 199 citationsread the source →

The GAD-7 questionnaire

The Generalized Anxiety Disorder (GAD-7) questionnaire is a seven-item, self-report anxiety questionnaire designed to assess the patient’s health status during the previous 2 weeks. The items enquire about the degree to which the patient has been bothered by feeling nervous, anxious or on edge, not being able to stop or control worrying, worrying too much about different things, having trouble relaxing, being so restless that it is hard to sit still, becoming easily annoyed or irritable and feeling afraid as if something might happen. The questionnaire was designed by Spitzer et al. [1] and published in 2006. It is quick to administer and is now used in research and clinical settings. The copyright is held by Pfizer Inc. but the questionnaire is free to use. The questionnaire has been validated for use as a screening tool and severity measure [1,2], in primary care [3] and in general populations [4]. Scores of 0, 1 or 2 are given for experiencing symptoms ‘not at all’, for ‘several days’, for ‘more than half the days’ and for ‘nearly every day’, respectively. The scores are then totalled and presented from 0 to 21. Scores of 5, 10 and 15 represent cut-off points for mild, moderate and severe anxiety, respectively. When screening for an anxiety disorder, a recommended cut-off point for referral for further evaluation is 10 or greater. Using the threshold score of 10, the GAD-7 has sensitivity of 89% and specificity of 82% for generalized anxiety disorder. It is also moderately good at screening for other anxiety disorders—panic disorder (sensitivity 74%, specificity 81%), social anxiety disorder (sensitivity 72%, specificity 80%) and post-traumatic stress disorder (sensitivity 66%, specificity 81%) [5]. The GAD-7 has been compared with other anxiety questionnaires such as the Penn State Worry Questionnaire for Measuring Response (PSWQMR) during Treatment of Generalized Anxiety Disorders, which is widely used in the USA. The GAD-7 was found, when compared with the PSWQMR to be more sensitive in detecting change in status, in the clinical setting. Both questionnaires had internal consistency (Cronbach’s alpha 0.79–0.91 (GAD-7) and 0.86–0.91 (PSWQMR), respectively) [6].

Occupational Medicine · 349 citationsread the source →