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Prevalence and risk of psychological distress, anxiety and depression in adolescent and young adult (AYA) cancer survivors: A systematic review and meta-analysis.

Background: Adolescent and young adult (AYA) cancer survivors (CS) face unique psychosocial challenges, which may affect their mental health. However, there are inconsistencies in AYA definitions and varying prevalence data on psychological distress, anxiety, and depression. We aimed to synthesize published literature on prevalence, risk, longitudinal changes, and predictors for these outcomes and estimate pooled prevalences. Methods: We searched for observational studies published in English before June 1 2022, in PubMed, PsycINFO, Scopus, and Web of Science. Two researchers extracted independently information on study characteristics, prevalence, and risk. The pooled prevalence (PP) of psychological distress, anxiety, and depression was estimated using random-effects models. Geographical region, treatment status, and assessment instruments were considered in stratified meta-analyses. Results: Sixty-eight studies were included in the systematic review and 57 in the meta-analyses. We estimated an overall prevalence of 32% (n = 30; 4226/15,213 AYAs; 95% CI, 23%-42%; I2  = 99%) for psychological distress, 29% for anxiety (n = 24; 2828/8751 AYAs; 95% CI, 23%-36%; I2  = 98%), and 24% (n = 35; 3428/16,638 AYAs; 95% CI, 18%-31%; I2  = 98%) for depression. The range of PP of psychological distress varied across geographical regions, treatment status, and assessment instruments. The PP of anxiety varied significantly across continents, while no variations were seen for depression. Studies found higher risks for psychological distress, anxiety, and depression in AYAs compared to older cancer survivors or cancer-free peers. Conclusions: Our research found that one in three AYA-CS experience psychological distress or anxiety and one in four are affected by depression, highlighting the need for specialized psychological services for AYA-CS in oncology settings and AYA-focused interventions.

Cancer medicine · meta-analysis · 103 citationsread the source →

Self-reported interoceptive accuracy and interoceptive attention differentially correspond to measures of visual attention and self-regard.

Background: Interoception, the perception of bodily functions and sensations, is a crucial contributor to cognition, emotion, and well-being. However, the relationship between these three processes is not well understood. Further, it is increasingly clear that dimensions of interoception differentially corresponds to these processes, yet this is only recently being explored. The present study addresses two important questions: Are subjective interoceptive accuracy and interoceptive attention related to self-regard and well-being? And are they related to exteroceptive (visual) attention? Methods: Participants (N = 98; 29% women; aged 23-64 years) completed: a battery of questionnaires to assess subjective accuracy (how well one predicts bodily sensations), interoceptive attention (a tendency to notice bodily signals), self-regard (self-esteem, self-image, life satisfaction), state negative affect (depression, anxiety, and stress), a self-esteem Implicit Association Task (a measure of implicit self-esteem), and a flanker task to assess visual selective attention. Subjective interoceptive accuracy and attention served as dependent variables. Correlations and principal component analysis was used to establish correlations among variables and determine how, or whether, these measures are associated with subjective interoceptive accuracy or attention. Results: Greater scores on measures of self-regard, implicit self-esteem, cognition and lower negative affect were broadly associated with greater subjective interoceptive accuracy. Conversely, only explicit self-esteem, satisfaction with life, and self-image corresponded to subjective interoceptive attention. An exploratory analysis with a more inclusive scale of interoceptive attention was conducted. Results of this exploratory analysis showed that the broader measure was a stronger correlate to self-regard than subjective interoceptive accuracy, though it, too, did not correlate with visual attention. In short, both subjective interoceptive accuracy and attention corresponded to well-being and mental health, but only accuracy was associated with exteroceptive attention. Conclusion: These results add to a growing literature suggesting different dimensions of (subjective) interoception differentially correspond to indices of well-being. The links between exteroceptive and interoceptive attention, and their association with merit further study.

PeerJ · 7 citationsread the source →

The effectiveness of third wave cognitive behavioural therapies for children and adolescents: A systematic review and meta-analysis.

Objectives: Third wave cognitive behavioural therapies are increasingly used with children and adolescents. This meta-analysis aimed to determine the effectiveness of four third-wave interventions (acceptance and commitment therapy, compassion focused therapy, mindfulness-based cognitive therapy, and metacognitive therapy) for youth. Methods: Four electronic databases were used to identify randomized controlled trials, which tested effects related to health, well-being and functioning. Sensitivity analyses considering study quality were conducted and moderators were explored. Results: The results based on 50 RCTs meeting inclusion criteria indicated emotional symptoms/internalizing problems (g = -.68, 95% CI -.98 to -.37, k = 43, N = 3265), behavioural difficulties/externalizing problems (g = -.62, 95% CI -1.01 to -.22, k = 23, N = 1659), interference from difficulties (g = -.46, 95% CI -.87 to -.05, k = 21, N = 1786), third wave processes (g = .39, 95% CI .17 to .62, k = 22, N = 1900), wellbeing/flourishing (g = .76, 95% CI .35 to 1.17, k = 21, N = 1303) and physical health/pain (g = .72, 95% CI .01 to 1.44, k = 9, N = 1171) yielded significant effects. Effect for quality of life (g = .62, 95% CI -.08 to 1.31, k = 12, N = 1271) was non-significant. When analysing only those studies rated moderate-high quality, third wave interventions yielded significant superiority effects compared to controls for emotional symptoms/internalizing problems (g = -.55, 95% CI -.82 to -.27, k = 28, N = 2110), interference from difficulties (g = -.48, 95% CI -.90 to -.05, k = 21, N = 1605), third wave processes (g = .27, 95% CI .11 to .43, k = 18, N = 1692), well-being/flourishing (g = .50, 95% CI .18 to .81, k = 16, N = 1063), and quality of life (g = .32, 95% CI .04 to .60, k = 10, N = 1212). Behavioural difficulties/externalizing problems (g = -.38, 95% CI -.86 to .10, k = 15, N = 1351) and physical health/pain (g = .52, 95% CI -.14 to 1.17, k = 8, N = 1139) ceased to be significant. Widespread heterogeneity raised concerns about generalizability and follow-up data was relatively sparse. Conclusions: This meta-analysis finds promising results for use of third wave CBT with youth, though the review has limitations.

The British journal of clinical psychology · meta-analysis · 19 citationsread the source →

Loneliness before and during the COVID-19 pandemic: A systematic review with meta-analysis.

The COVID-19 pandemic and measures aimed at its mitigation, such as physical distancing, have been discussed as risk factors for loneliness, which increases the risk of premature mortality and mental and physical health conditions. To ascertain whether loneliness has increased since the start of the pandemic, this study aimed to narratively and statistically synthesize relevant high-quality primary studies. This systematic review with meta-analysis was registered at PROSPERO (ID CRD42021246771). Searched databases were PubMed, PsycINFO, Cochrane Library/Central Register of Controlled Trials/EMBASE/CINAHL, Web of Science, the World Health Organization (WHO) COVID-19 database, supplemented by Google Scholar and citation searching (cutoff date of the systematic search December 5, 2021). Summary data from prospective research including loneliness assessments before and during the pandemic were extracted. Of 6,850 retrieved records, 34 studies (23 longitudinal, 9 pseudolongitudinal, 2 reporting both designs) on 215,026 participants were included. Risk of bias (RoB) was estimated using the risk of bias in non-randomised studies-of interventions (ROBINS-I) tool. Standardized mean differences (SMD, Hedges' g) for continuous loneliness values and logOR for loneliness prevalence rates were calculated as pooled effect size estimators in random-effects meta-analyses. Pooling studies with longitudinal designs only (overall N = 45,734), loneliness scores (19 studies, SMD = 0.27 [95% confidence interval = 0.14-0.40], Z = 4.02, p < .001, I 2 = 98%) and prevalence rates (8 studies, logOR = 0.33 [0.04-0.62], Z = 2.25, p = .02, I 2 = 96%) increased relative to prepandemic times with small effect sizes. Results were robust with respect to studies' overall RoB, pseudolongitudinal designs, timing of prepandemic assessments, and clinical populations. The heterogeneity of effects indicates a need to further investigate risk and protective factors as the pandemic progresses to inform targeted interventions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The American psychologist · meta-analysis · 317 citationsread the source →

Psychosocial interventions following self-harm in adults: a systematic review and meta-analysis.

Background: Self-harm (intentional acts of non-fatal self-poisoning or self-injury) is common, particularly in young adults aged 15-35 years, often repeated, and strongly associated with suicide. Effective aftercare of individuals who self-harm is therefore important. We have undertaken a Cochrane systematic review and meta-analysis of the effectiveness of psychosocial interventions for self-harm in adults. Methods: We searched five electronic databases (CCDANCTR-Studies and References, CENTRAL, MEDLINE, Embase, and PsycINFO) between Jan 1, 1998, and April 29, 2015, for randomised controlled trials of psychosocial interventions for adults after a recent (within 6 months) episode of self-harm. Most interventions were assessed in single trials. We report results for interventions for which at least three randomised controlled trials comparing interventions with treatment as usual have been published and hence might contribute to clinical guidance. The primary outcome was repetition of self-harm at the conclusion of treatment and at 6, 12, and 24 months' follow-up analysed, when available, with the intention-to-treat method; if this was not possible, we analysed with all available case data. Findings: We identified 29 non-overlapping randomised controlled trials with three independent trials of the same intervention. Cognitive-behavioural-based psychotherapy (CBT; comprising cognitive-behavioural and problem-solving therapy) was associated with fewer participants repeating self-harm at 6 months' (odds ratio 0·54, 95% CI 0·34-0·85; 12 trials; n=1317) and at 12 months' follow-up (0·80, 0·65-0·98; ten trials; n=2232). There were also significant improvements in the secondary outcomes of depression, hopelessness, suicidal ideation, and problem solving. Patients receiving dialectical behaviour therapy (in three trials) were not less likely to repeat self-harm compared with those provided with treatment as usual at 6 months (odds ratio [OR] 0·59, 95% CI 0·16-2·15; n=267, three trials) or at 12 months (0·36, 0·05-2·47; n=172, two trials). However, the secondary endpoint of frequency of self-harm was associated with a significant reduction with use of dialectical behaviour therapy (mean difference -18·82, 95% CI -36·68 to -0·95). Four trials each of case management (OR 0·78, 95% CI 0·47-1·30; n=1608) and sending regular postcards (OR 0·87, 95% CI 0·62-1·23; n=3277) did not reduce repetition of self-harm. Interpretation: CBT seems to be effective in patients after self-harm. Dialectical behaviour therapy did not reduce the proportion of patients repeating self-harm but did reduce the frequency of self-harm. However, aside from CBT, there were few trials of other promising interventions, precluding firm conclusions as to their effectiveness. Funding: National Institute for Health Research.

The lancet. Psychiatry · meta-analysis · 141 citationsread the source →

Socioeconomic gradients in the effects of universal school-based health behaviour interventions: a systematic review of intervention studies.

Background: Socioeconomic inequalities in health behaviour emerge in early life before tracking into adulthood. Many interventions to improve childhood health behaviours are delivered via schools, often targeting poorer areas. However, targeted approaches may fail to address inequalities within more affluent schools. Little is known about types of universal school-based interventions which make inequalities better or worse. Methods: Seven databases were searched using a range of natural language phrases, to identify trials and quasi-experimental evaluations of universal school-based interventions focused on smoking, alcohol, diet and/or physical activity, published from 2008-14. Articles which examined differential effects by socioeconomic status (N = 20) were synthesised using harvest plot methodology. Content analysis of 98 intervention studies examined potential reasons for attention or inattention to effects on inequality. Results: Searches identified approximately 12,000 hits. Ninety-eight evaluations were identified, including 90 completed studies, of which 20 reported effects on SES inequality. There were substantial geographical biases in reporting of inequality, with only 1 of 23 completed North American studies testing differential effects, compared to 15 out of 52 completed European studies. Studies reported a range of positive, neutral or negative SES gradients in effects. All studies with a negative gradient in effect (i.e. which widened inequality) included educational components alone or in combination with environmental change or family involvement. All studies with positive gradients in effects included environmental change components, alone or combined with education. Effects of multi-level interventions on inequality were inconsistent. Content analyses indicated that in approximately 1 in 4 studies SES inequalities were discussed in defining the problem or rationale for intervention. Other potential barriers to testing effect on inequality included assumptions that universal delivery guaranteed universal effect, or that interventions would work better for poorer groups because they had most to gain. Conclusions: Universal school-based interventions may narrow, widen or have no effect on inequality. There is a significant need for more routine testing of the effects of such interventions on inequality to enable firmer conclusions regarding types of interventions which affect inequality. Prospero registration number: CRD42014014548.

BMC public health · systematic review · 57 citationsread the source →

Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990-2021: a systematic analysis from the Global Burden of Disease Study 2021.

Background: Lower respiratory infections (LRIs) are a major global contributor to morbidity and mortality. In 2020-21, non-pharmaceutical interventions associated with the COVID-19 pandemic reduced not only the transmission of SARS-CoV-2, but also the transmission of other LRI pathogens. Tracking LRI incidence and mortality, as well as the pathogens responsible, can guide health-system responses and funding priorities to reduce future burden. We present estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 of the burden of non-COVID-19 LRIs and corresponding aetiologies from 1990 to 2021, inclusive of pandemic effects on the incidence and mortality of select respiratory viruses, globally, regionally, and for 204 countries and territories. Methods: We estimated mortality, incidence, and aetiology attribution for LRI, defined by the GBD as pneumonia or bronchiolitis, not inclusive of COVID-19. We analysed 26 259 site-years of mortality data using the Cause of Death Ensemble model to estimate LRI mortality rates. We analysed all available age-specific and sex-specific data sources, including published literature identified by a systematic review, as well as household surveys, hospital admissions, health insurance claims, and LRI mortality estimates, to generate internally consistent estimates of incidence and prevalence using DisMod-MR 2.1. For aetiology estimation, we analysed multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature data using a network analysis model to produce the proportion of LRI deaths and episodes attributable to the following pathogens: Acinetobacter baumannii, Chlamydia spp, Enterobacter spp, Escherichia coli, fungi, group B streptococcus, Haemophilus influenzae, influenza viruses, Klebsiella pneumoniae, Legionella spp, Mycoplasma spp, polymicrobial infections, Pseudomonas aeruginosa, respiratory syncytial virus (RSV), Staphylococcus aureus, Streptococcus pneumoniae, and other viruses (ie, the aggregate of all viruses studied except influenza and RSV), as well as a residual category of other bacterial pathogens. Findings: Globally, in 2021, we estimated 344 million (95% uncertainty interval [UI] 325-364) incident episodes of LRI, or 4350 episodes (4120-4610) per 100 000 population, and 2·18 million deaths (1·98-2·36), or 27·7 deaths (25·1-29·9) per 100 000. 502 000 deaths (406 000-611 000) were in children younger than 5 years, among which 254 000 deaths (197 000-320 000) occurred in countries with a low Socio-demographic Index. Of the 18 modelled pathogen categories in 2021, S pneumoniae was responsible for the highest proportions of LRI episodes and deaths, with an estimated 97·9 million (92·1-104·0) episodes and 505 000 deaths (454 000-555 000) globally. The pathogens responsible for the second and third highest episode counts globally were other viral aetiologies (46·4 million [43·6-49·3] episodes) and Mycoplasma spp (25·3 million [23·5-27·2]), while those responsible for the second and third highest death counts were S aureus (424 000 [380 000-459 000]) and K pneumoniae (176 000 [158 000-194 000]). From 1990 to 2019, the global all-age non-COVID-19 LRI mortality rate declined by 41·7% (35·9-46·9), from 56·5 deaths (51·3-61·9) to 32·9 deaths (29·9-35·4) per 100 000. From 2019 to 2021, during the COVID-19 pandemic and implementation of associated non-pharmaceutical interventions, we estimated a 16·0% (13·1-18·6) decline in the global all-age non-COVID-19 LRI mortality rate, largely accounted for by a 71·8% (63·8-78·9) decline in the number of influenza deaths and a 66·7% (56·6-75·3) decline in the number of RSV deaths. Interpretation: Substantial progress has been made in reducing LRI mortality, but the burden remains high, especially in low-income and middle-income countries. During the COVID-19 pandemic, with its associated non-pharmaceutical interventions, global incident LRI cases and mortality attributable to influenza and RSV declined substantially. Expanding access to health-care services and vaccines, including S pneumoniae, H influenzae type B, and novel RSV vaccines, along with new low-cost interventions against S aureus, could mitigate the LRI burden and prevent transmission of LRI-causing pathogens. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care (UK).

The Lancet. Infectious diseases · systematic review · 388 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 →

Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, US-based trial.

Background: A pneumococcal conjugate vaccine (PCV) specifically focused on serotypes associated with adult residual disease burden is urgently needed. We aimed to assess V116, an investigational 21-valent PCV, that contains pneumococcal polysaccharides (PnPs), which account for 74-94% of invasive pneumococcal disease in adults aged 65 years or older. Methods: We did a phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, non-inferiority and superiority trial. The phase 1 study was done at two clinical sites in the USA, and the phase 2 study was done in 18 clinical sites in the USA. Eligible participants were healthy adults with or without chronic medical conditions assessed as stable, aged 18-49 years in the phase 1 trial and aged 50 years or older in the phase 2 trial. Participants were excluded if they had a history of invasive pneumococcal disease or other culture-positive pneumococcal disease within the past 3 years, known hypersensitivity to a vaccine component, known or suspected impairment of immunological function, were pregnant or were breastfeeding, or had previously received any pneumococcal vaccine. Participants had to abstain from sexual activity or use protocol approved contraception. All participants were centrally randomly assigned to a vaccine group using an interactive response technology system. Participants and investigators were masked to group assignment. In phase 1, participants were randomly assigned (1:1:1) to receive a single dose of V116-1 (2 μg per pneumococcal polysaccharide [PnP] per 0·5 mL) or V116-2 (4 μg per PnP per 1·0 mL) or the 23-valent unconjugated PnP vaccine, PPSV23 (25 μg per PnP per 0·5 mL). In phase 2, participants were randomly assigned (1:1) to receive one dose of V116 (4 μg per PnP per 1·0 mL) or PPSV23 (25 μg per PnP per 0·5 mL), stratified by age. Safety analyses included all randomly assigned participants who received study vaccine; immunogenicity analyses were per protocol. For both phases, the primary safety outcome was the proportion of participants with solicited injection-site adverse events and solicited systemic adverse events up to day 5 after vaccination and the proportion of participants with vaccine-related serious adverse events to 6 months after vaccination. In phase 2, primary immunogenicity outcomes were to test non-inferiority of V116 compared with PPSV23 as measured by serotype-specific opsonophagocytic antibody geometric mean titres (OPA-GMT) ratios for the serotypes common to the two vaccines at 30 days after vaccination (using a 0·33 margin) and to test superiority of V116 compared with PPSV23 as measured by serotype-specific OPA-GMT ratios for the serotypes unique to V116 at 30 days after vaccination (using a 1·0 margin). This trial is registered with Clinicaltrials.gov, NCT04168190. Findings: Between Dec 6 and 26, 2019, 92 volunteers were screened and 90 (98%) enrolled for phase 1 (59 [66%] women; 31 [34%] men); 30 participants were assigned to each group and received study vaccine. 30 (100%) participants in the V116-1 group, 29 (97%) in the V116-2 group, and 30 (100%) participants in the PPSV23 group were included in the per-protocol immunogenicity evaluation. From Sept 23, 2020, to Jan 12, 2021, 527 volunteers were screened, and 510 (97%) participants were enrolled in the phase 2 trial. 508 participants (>99%; 254 [100%] of 254 participants randomly assigned to the V116 group and 254 [99%] of 256 randomly assigned to PPSV23 group) received study vaccine (281 [55%] women; 227 [45%] men). 252 (99%) of 254 of participants in the V116 group and 254 (99%) of 256 participants in the PPSV23 group were included in the primary immunogenicity analyses. There were no vaccine-related serious adverse events or vaccine-related deaths in either study phase. In both phases, the most common solicited injection site adverse event was injection site pain (phase 1 22 [73%] participants in V116-1 group, 23 [77%] participants in V116-2 group, and 17 [57%] participants in the PPSV23 group; phase 2 118 [46%] of 254 participants in the V116 group and 96 [38%] of 254 in the PPSV23 group]. The most common solicited systemic adverse events in phase 1 was fatigue (eight [27%] participants in the V116-1 group, eight [27%] participants in the V116-2 group, and five [17%] participants in PPSV23 group) and myalgia (eight [27%] participants in the V116-1 group, nine (30%) participants in the V116-2 group, and four (13%) participants in the PPSV23 group]. In phase 2, the most frequently reported solicited systemic adverse event was fatigue (49 [19%] participants in V116 group, and 31 [12%] participants in PPSV23 group). In both phases, most of the solicited adverse events in all vaccine groups were mild and of short duration (≤3 days). V116 met non-inferiority criteria compared with PPSV23 for the 12 shared serotypes and met superiority criteria compared to PPSV23 for the nine unique serotypes. Interpretation: V116 was well tolerated with a safety profile generally similar to PPSV23; consistent with licensed pneumococcal conjugate vaccines. Functional OPA antibodies were induced to all V116 vaccine serotypes. The vaccine was non-inferior to PPSV23 for the 12 serotypes common to both vaccines and superior to PPSV23 for the nine unique serotypes in V116. Our findings support the development of V116 for prevention of pneumococcal disease in adults. Funding: Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA.

The Lancet. Infectious diseases · randomised controlled trial · 73 citationsread the source →

Gamma-hydroxybutyrate (GHB) for treatment of alcohol withdrawal and prevention of relapses.

Background: Chronic excessive alcohol consumption may lead to dependence, and to alcohol withdrawal syndrome (AWS) in case of abrupt drinking cessation. Gamma-hydroxybutyric acid (GHB) can prevent and suppress withdrawal symptoms, and improve the medium-term abstinence rate. A clear balance between effectiveness and harmfulness has not been yet established. Objectives: To evaluate the efficacy and safety of GHB for treatment of AWS and prevention of relapse Search strategy: We searched Cochrane Drugs and Alcohol Group' Register of Trials (October 2008), PubMed, EMBASE, CINAHL (January 2005 - October 2008), EconLIT (1969 to February 2008), reference list of retrieved articles Selection criteria: Randomized controlled trials (RCTs) and Controlled Prospective Studies (CPS) evaluating the efficacy and the safety of GHB vs placebo or other pharmacological treatments. Data collection and analysis: Three authors independently extracted data and assessed the methodological quality of studies. Main results: Thirteen RCTs were included. Eleven studies were conducted in Italy. For withdrawal syndrome, comparing GHB 50mg with placebo, results from 1 study, 23 participants favour GHB for withdrawal symptoms: WMD -12.1 (95% CI, -15.9 to -8.29) and side effects were more frequent in the placebo group: RR 16.2 (95% CI, 1.04 to 254.9).In the comparison with Chlormetiazole, for GHB 50mg, results from 1 study, 21 participants favour GHB for withdrawal symptoms: MD -3.40 (95% CI -5.09 to -1.71), for GHB 100mg, results from 1 study, 98 participants favour anticonvulsants for side effects: RR 1.84 (95% CI 1.19 to 2.85).At mid-term, comparing GHB with placebo, results favour GHB for abstinence rate (RR 5.35; 1.28-22.4), controlled drinking (RR 2.13; 1.07-5.54), relapses (RR 0.36; 0.21-0.63), and number of daily drinks (WMD -4.60; -6.18 to -3.02). GHB performed better than NTX and Disulfiram on abstinence (RR 2.59; 1.35-4.98, RR 1.66; 0.99-2.80 respectively). The association of GHB and NTX was better than NTX on abstinence (RR 12.2; 1.79-83.9), as well was the association of NTX, GHB and Escitalopram versus Escitalopram alone (RR 4.58; 1.28-16.5). For Alcohol Craving Scale results favour GHB versus placebo (WMD -1.90; -2.45 to 1.35) and Disulfiram (WMD -1.40; -1.86 to-0.94). Authors' conclusions: GHB 50mg is effective compared to placebo in the treatment of AWS, and in preventing relapses in previously detoxified alcoholics at 3 months follow-up, but the results of this review do not provide sufficient evidence in favour of GHB compared to benzodiazepines and Chlormethiazole for AWS prevention. GHB is better than NTX and Disulfiram in maintaining abstinence and it has a better effect on craving than placebo and Disulfiram. Side effects of GHB are not statistically different from those with BZD, NTX or Disulfiram. However, concern has been raised regarding the risk of developing addiction, misuse or abuse, especially in polydrug abusers.

The Cochrane database of systematic reviews · meta-analysis · 58 citationsread the source →

Telomere attrition is associated with inflammation, low fetuin-A levels and high mortality in prevalent haemodialysis patients.

Introduction: Chronic kidney disease (CKD) predisposes to a 10- to 20-fold increased cardiovascular risk. Patients undergo accelerated atherogenesis and vascular ageing. We investigated whether telomere attrition, a marker of cell senescence, contributes to this increased mortality risk. Methods: This is a cross-sectional study in prevalent haemodialysis patients [n = 175; 98 Males; median (range) age: 66 (23-86) years]. Biochemical markers of oxidative stress and inflammatory status were measured in relation to the patient's leucocyte telomere length. Overall mortality was assessed after a median of 31 (range 2-42) months. Results: Telomere length was shorter in CKD men, despite women being older (average +/- SD 6.41 +/- 1.23 vs. 6.96 +/- 1.48 kb, P = 0.002). Telomere length was associated with age (rho = -0.18, P = 0.01), fetuin-A (rho = 0.26, P = 0.0004), high-sensitivity C-reactive protein (rho = -0.21, P = 0.005) and IL-6 (rho = -0.17, P = 0.02). In a multivariate logistic regression (pseudo r(2) = 0.14), telomere length was associated with age >65 years (odds ratio: 2.11; 95% CI: 1.10, 4.06), sex (2.01; 1.05, 3.86), fetuin-A (1.85; 0.97, 3.50) and white blood cell count (2.04; 1.02, 4.09). Receiver operating characteristic curves identified a telomere length < 6.28 kb as a fair predictor of mortality. Finally, reduced telomere length was associated with increased mortality, independently of age, gender and inflammation (likelihood ratio 41.6, P < 0.0001), but dependently on fetuin-A levels. Conclusion: Age and male gender seem to be important contributors to reduced telomere length in CKD patients, possibly via persistent inflammation. Reduced telomere length also contributes to the mortality risk of these patients through pathways that could involve circulating levels of fetuin-A.

Journal of internal medicine · 134 citationsread the source →

The Tailored Activity Program to reduce behavioral symptoms in individuals with dementia: feasibility, acceptability, and replication potential.

Purpose: The Tailored Activity Program (TAP) is a home-based occupational therapy intervention shown to reduce behavioral symptoms and caregiver burden in a randomized trial. This article describes TAP, its assessments, acceptability, and replication potential. Design and methods: TAP involves 8 sessions for a period of 4 months. Interventionists identify preserved capabilities, previous roles, habits, and interests of individuals with dementia; develop activities customized to individual profiles; and train families in activity use. Interventionists documented time spent and ease conducting assessments, and observed receptivity of TAP. For each implemented prescribed activity, caregivers reported the amount of time their relative spent in activity and perceived benefits. Results: The TAP assessment, a combination of neuropsychological tests, standardized performance-based observations, and clinical interviewing, yielded information on capabilities from which to identify and tailor activities. Assessments were easy to administer, taking an average of two 1-hr sessions. Of 170 prescribed activities, 81.5% were used, for an average of 4 times for 23 min by families between treatment sessions for a period of months. Caregivers reported high confidence in using activities, being less upset with behavioral symptoms (86%), and enhanced skills (93%) and personal control (95%). Interventionists observed enhanced engagement (100%) and pleasure (98%) in individuals with dementia during sessions. Implications: TAP offers families knowledge of their relative's capabilities and easy-to-use activities. The program was well received by caregivers. Prescribed activities appeared to be pleasurable and engaging to individuals with dementia. TAP merits further evaluation to establish efficacy with larger more diverse populations and consideration as a nonpharmacological approach to manage behavioral symptoms.

The Gerontologist · randomised controlled trial · 116 citationsread the source →

Clinical and cost-effectiveness of cognitive behaviour therapy for health anxiety in medical patients: a multicentre randomised controlled trial.

Background: Health anxiety has been treated by therapists expert in cognitive behaviour therapy with some specific benefit in some patients referred to psychological services. Those in hospital care have been less often investigated. Following a pilot trial suggesting efficacy we carried out a randomised study in hospital medical clinics. Methods: We undertook a multicentre, randomised trial on health anxious patients attending cardiac, endocrine, gastroenterological, neurological, and respiratory medicine clinics in secondary care. We included those aged 16-75 years, who satisfied the criteria for excessive health anxiety, and were resident in the area covered by the hospital, were not under investigation for new pathology or too medically unwell to take part. We used a computer-generated random scheme to allocate eligible medical patients to an active treatment group of five-to-ten sessions of adapted cognitive behaviour therapy (CBT-HA group) delivered by hospital-based therapists or to standard care in the clinics. The primary outcome was change in health anxiety symptoms measured by the Health Anxiety Inventory at 1 year and the main secondary hypothesis was equivalence of total health and social care costs over 2 years, with an equivalence margin of £150. Analysis was by intention to treat. The study is registered with controlled-trials.com, ISRCTN14565822. Findings: Of 28,991 patients screened, 444 were randomly assigned to receive either adapted cognitive behaviour therapy (CBT-HA group, 219 participants) or standard care (standard care group, 225), with 205 participants in the CBT-HA group and 212 in the standard care group included in the analyses of the primary endpoints. At 1 year, improvement in health anxiety in the patients in the CBT-HA group was 2·98 points greater than in those in the standard care group (95% CI 1·64-4·33, p<0·0001), and twice as many patients receiving cognitive behaviour therapy achieved normal levels of health anxiety compared with those in the control group (13·9% vs 7·3%; odds ratio 2·15, 95% CI 1·09-4·23, p=0·0273). Similar differences were observed at 6 months and 2 years, and there were concomitant reductions in generalised anxiety and, to a lesser extent, depression. Of nine deaths, six were in the control group; all were due to pre-existing illness. Social functioning or health-related quality of life did not differ significantly between groups. Equivalence in total 2-year costs was not achieved, but the difference was not significant (adjusted mean difference £156, 95% CI -1446 to 1758, p=0·848). Interpretation: This form of adapted cognitive behaviour therapy for health anxiety led to sustained symptomatic benefit over 2 years, with no significant effect on total costs. It deserves wider application in medical care. Funding: National Institute for Health Research Health Technology Assessment Programme.

Lancet (London, England) · randomised controlled trial · 96 citationsread the source →

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

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

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

Improving newborn preventive services at the birth hospitalization: a collaborative, hospital-based quality-improvement project.

Objective: The goal was to test the effectiveness of a statewide, collaborative, hospital-based quality-improvement project targeting preventive services delivered to healthy newborns during the birth hospitalization. Methods: All Vermont hospitals with obstetric services participated. The quality-improvement collaborative (intervention) was based on the Breakthrough Series Collaborative model. Targeted preventive services included hepatitis B immunization; assessment of breastfeeding; assessment of risk of hyperbilirubinemia; performance of metabolic and hearing screens; assessment of and counseling on tobacco smoke exposure, infant sleep position, car safety seat fit, and exposure to domestic violence; and planning for outpatient follow-up care. The effect of the intervention was assessed at the end of an 18-month period. Preintervention and postintervention chart audits were conducted by using a random sample of 30 newborn medical charts per audit for each participating hospital. Results: Documented rates of assessment improved for breastfeeding adequacy (49% vs 81%), risk for hyperbilirubinemia (14% vs 23%), infant sleep position (13% vs 56%), and car safety seat fit (42% vs 71%). Documented rates of counseling improved for tobacco smoke exposure (23% vs 53%) and car safety seat fit (38% vs 75%). Performance of hearing screens also improved (74% vs 97%). No significant changes were noted in performance of hepatitis B immunization (45% vs 30%) or metabolic screens (98% vs 98%), assessment of tobacco smoke exposure (53% vs 67%), counseling on sleep position (46% vs 68%), assessment of exposure to domestic violence (27% vs 36%), or planning for outpatient follow-up care (80% vs 71%). All hospitals demonstrated preintervention versus postintervention improvement of > or = 20% in > or = 1 newborn preventive service. Conclusions: A statewide, hospital-based quality-improvement project targeting hospital staff members and community physicians was effective in improving documented newborn preventive services during the birth hospitalization.

Pediatrics · cohort or longitudinal · 30 citationsread the source →

Clinical Presentation of Left Atrial Cardiac Myxoma

Introduction Cardiac myxoma is the most frequent “benign” tumor of the heart and presents an important diagnostic challenge (4,43,47). Myxomas may resemble many cardiovascular or systemic diseases, and can arise in any of the cardiac chambers, although 75% occur in the left atrium. Most cases of atrial myxomas are now diagnosed in living patients, allowing successful surgical extirpation (1,3,30,44,53). Before the introduction of angiocardiography in 1951, cardiac myxoma diagnosis was made only at autopsy (22). The first successful surgical removal of an atrial myxoma was performed in 1954 (35,47). In 1959, the first M-mode echocardiogram of a left atrial myxoma was reported (16). Indeed, the introduction of echocardiography has provided an important noninvasive means of diagnosis for cardiac myxomas (55). Thus, the diagnosis of small myxomas (less than 5 cm in size and asymptomatic) is becoming easier. We report here the experience of a French cardiovascular center in the clinical presentation of left atrial myxomas. The large number of patients in this series allowed us to perform an analytic, clinicopathologic study. Patients and Methods We reviewed the 112 cases of left atrial myxoma seen at 1 institution (Hôpital Louis Pradel, Lyons, France) over a 40-year period (1959–1998). In all cases the diagnosis was established before surgical removal. The patients’ medical records were reviewed, and data concerning clinical presentation, diagnostic methods, and postoperative course were collected. Histopathologic slides were reviewed for all cases by the same pathologist (RL). Other locations where cardiac myxoma occurred during that time period were the right atrium (15 cases), left ventricle (2 cases), and right ventricle (1 case). Follow-up information was obtained by contacting either the patients or the attending physicians, and a standardized questionnaire was completed for each case. Statistical analysis A chi-square test, or the Fisher exact test when required, was performed for all qualitative variables, and odds ratios (OR) with 95% confidence intervals (95% CI) were computed. For ordinal variables a Wilcoxon rank sum test was used. Data analysis was performed using SAS (Statistical Analysis System, SAS Institute Inc., Cary, NC). The variables studied in the statistical analysis were 1) sex and age, period of diagnosis (before or after echocardiography was available), delay to diagnosis (delay between the first symptoms and diagnosis), possible systematic (serendipitous) discovery; 2) size of the tumor (> or < 5 cm), tumor surface appearance (smooth or villous); 3) the main symptoms: cardiac (cardiac failure, malaise or syncope, chest pain or palpitations), embolic (cerebral, coronary, or peripheral artery), systemic (fever, weight loss, or pseudo-connective tissue disease signs), or neurologic (stroke, vertigo, epilepsy, coma, or other signs); 4) cardiac auscultation modifications (pseudo-mitral signs, “tumor plop”, nonspecific other signs); 5) possible chest X-ray abnormalities (left cardiac failure signs, cardiomegaly, pleural effusion, left atrium enlargement, visible myxoma when calcified), electrocardiogram (ECG) alterations (arrhythmias or conduction disturbances, ST-segment and T-wave shifts, left atrial hypertrophy, and nonspecific signs), or serologic test abnormalities (elevated erythrocyte sedimentation rate [ESR], anemia). Results Patient characteristics The study group included 72 women, (64% of the whole sample; median age, 53 yr; range, 23–84 yr) and 40 men (36% of the sample; median age, 58 yr, range, 5–77 yr). Forty-six patients (41% of the sample, 31 women, 15 men) were less than 50 years old, 47 (42%, 31 women, 16 men) were between 50 and 70 years, and 19 (17%, 10 women, 9 men) were older than 70. Age distribution was homogenous in men, but most female patients were between 40 and 60 years old (Figure 1).Fig. 1: Age distribution of 112 patients with left atrial myxoma. The clinical and laboratory features of left atrial myxoma in our series are presented in Table 1. The different frequencies of clinical and laboratory signs according to sex and age are detailed in Table 2. Male patients were more at risk than females for embolic complications and for neurologic symptoms; females were more at risk than males to develop systemic symptoms such as fever; younger patients (age <50 yr) had more neurologic symptoms and cardiac auscultation abnormalities than older patients (age >50 yr).TABLE 1: Clinical and laboratory features of left atrial myxoma (112 cases)TABLE 2: Frequencies of clinical and laboratory signs by sex and age*We divided the patients into 2 groups according to the pre-and post-echocardiography periods: 1) between 1959 and 1977, when the only diagnostic methods were angiocardiography and cardiac cathe-terization, only 14 patients (12.5%) underwent surgery; 2) since 1977, with 2-dimensional echocardiography use (transthoracic, then transesophageal), about 5 patients per year have undergone surgery for left atrial myxoma (98 patients, 87.5%). The sex ratio and age ranges are similar in these 2 patient groups, but other differences can be identified (Table 3). Before 1977, most patients were diagnosed on the basis of serologic or blood test abnormalities (particularly elevated ESR) and radiologic abnormalities; chest X-ray evidence of cardiac failure or left atrium enlargement was particularly prevalent in patients diagnosed before 1977 compared with those diagnosed after 1977 (p = 0.006 and p = 0.02, respectively).TABLE 3: Symptoms by year of diagnosis*Delay before surgery In our series, the time interval between symptoms onset and diagnosis (surgical removal) varied from 0 to 126 months (median, 4 mo). The median delay before surgery was 5.5 months before 1977, and 3 months after 1977; the difference is not significant. The median delay to diagnosis increased significantly when cardiac symptoms were present; there was no significant difference for the other symptoms (Table 4).TABLE 4: Delay to diagnosis by year and by principal clinical symptoms*Initial symptoms ( Figure 2) For 11 patients, the left atrial myxoma diagnosis was a mere chance, or serendipitous, discovery (“systematic findings” in Figure 2). Among these patients, in 9 cases echocardiography (8 cases) or computed tomography (CT) (1 case) was performed for another indication and allowed a diagnosis of myxoma. For 2 patients, echocardiography had been systematically performed during follow-up for surgery on a right atrial myxoma. Fig. 2: Initial symptoms of left atrial myxoma (112 cases).The most common initial symptoms of left atrial myxoma in our series were related to mitral valve obstruction: dizziness and occasionally syncope, palpitations, dyspnea, cough, pulmonary edema, or congestive heart failure were observed in 58 patients. Eight patients showed atypical paroxysmal clinical manifestations: chest pain, hemoptysis, limb claudication, thoracic noise, shortness of breath, or syncope when reclining. Embolic manifestations suggested myxoma in 18 patients. Constitutional or general systemic signs appeared as initial manifestations for 17 patients: myalgia, muscle weakness, arthralgia, fever, weight loss, fatigue, and Raynaud syndrome. Clinical features at diagnosis All patients presented with at least 1 or more symptoms of the classic triad: 1) obstructive cardiac signs; 2) embolic signs; and 3) constitutional or systemic manifestations (See Table 1). 1) Intracardiac obstruction signs occurred in 75 patients. Pulmonary edema or progressive congestive cardiac failure (dyspnea, orthopnea) were the most common symptoms (n = 48). Malaise or syncope occurred in 16 cases. Two patients experienced cardiac arrest before surgery and fully recovered after resuscitation. Other nonspecific cardiac symptoms were present in 34 patients: cough, thoracic pain, palpi-tations, myocardial infarction due to coronary embolism. Malaise, palpitations, or thoracic pain could vary with body postural changes. 2) Signs of embolism were present in 33 patients, either with 1 (n = 25) or several (n = 8) locations. Embolic locations were the central nervous system (n = 24), in 1 case in the retinal artery, the upper and lower extremities (n = 15), and the coronary arteries (n = 4). 3) Thirty-eight patients presented with systemic or constitutional symptoms. These symptoms were obviously nonspecific, including fever (n = 22), weight loss or fatigue (n = 20), and immunologic diseases mimicking symptoms such as myalgia, muscle weakness, arthralgia, or Raynaud syndrome (n = 6). 4) Other clinical presentations 4.1) Twenty-nine patients had neurologic symptoms, particularly transient or permanent motor or sensory neurologic deficiencies (n = 23), when cerebral emboli were present (stroke). Three of these patients developed multiple cerebral aneurysms, induced by cerebral emboli. Three patients had epileptic fits, or multilocular sclerosis mimicking symptoms. Six patients also suffered from other neurologic manifestations, such as vertigo or coma. One patient with streptococcal meningitis underwent surgery for a supposed antibiotic-resistant endocarditis suggested by echocardiographic findings, but surgery uncovered an incidental noninfected myxoma. 4.2) One patient had fever and positive blood cultures for Streptococcus viridans. 4.3) Three patients were investigated for liver abnormalities connected in fact with right cardiac failure. 4.4) For 3 patients, the main symptoms were abdominal pain or hemoptysis. Physical examination (cardiac auscultation) On cardiac auscultation 72 patients (64%) had abnormal findings, 18 (16%) of them with postural changes or with time examination modifications. These murmurs looked like significant mitral stenosis findings: apical diastolic or presystolic murmur (n = 60, 53%). A tumor plop was heard in 17 patients (15%), all before 1989. Other auscultatory features were changes in preexisting murmurs, gallops, or modification of the first (split) or second heart sound (n = 12, 11%). A significant was observed between cardiac auscultation abnormalities and 1) systemic symptoms (fever, weight loss or and 2) cardiac symptoms and signs (cardiac failure, (Table no between auscultatory signs and embolic or neurologic symptoms was between clinical The most frequent laboratory was in patients Table 1). in men, in was observed in 15 patients. blood or was present in patients. The between these serologic abnormalities and systemic manifestations was significant Table there was no significant between serologic signs and or neurologic symptoms. abnormalities of the patients (n = had abnormal Table 1). atrial was the most frequent (n = or or conduction were Other were ST-segment abnormalities (n = or nonspecific abnormalities (n = hypertrophy, The of abnormalities with systemic manifestations and cardiac signs was significant Table was no significant with embolic or neurologic symptoms. were abnormal in patients Table 1). included pulmonary or congestive heart failure signs (n = and nonspecific (n = atrial enlargement (n = that made the tumor visible (n = and pleural were (n = The of radiologic abnormalities with systemic and cardiac manifestations was significant Table X-ray abnormalities were significantly less frequent in patients with embolic or neurologic methods Before 1977, all cases were diagnosed by angiocardiography with left heart (n = 1977, echocardiography was the diagnostic (n = only M-mode echocardiography was (Figure 3). 2-dimensional and particularly echocardiography the methods in many cases. For 2 patients the diagnosis was established by or 3: A myxoma is seen in the left The diagnosis of myxoma was obtained after surgical tumor for all cases. On the tumor from 1 cm to 15 The size was for was than 5 cm in and in cases had been during The weight of the from 15 to In our series of the myxomas were with a cm), and were the left atrial myxomas in our series, the and from the left atrial with only a other left and small mitral valve The myxoma surface was studied in was or in of these (n = and (Figure 4) in the other cases (n = The less common or (Figure 5) myxomas had a surface that of multiple or and with a to (Figure 4: left atrial myxoma after left atrial were on the of myxoma in an of an The myxoma had a or an and a were the The surface of the tumor was by a of was observed in of the cases. We with a myxoma from with a and or different of 1) (Figure with or by then by 2) (Figure with many or in the of the cases were left atrial of them with and with were myxomas with All were observed in patients with myxoma and atrial myxoma with with myxoma in atrial myxoma with or myxoma in significant could be between myxoma size or 5 and diagnosis or or of or serologic symptoms or signs (Table 6). a myxoma size cm was significantly with cardiac symptoms, auscultatory signs, and and chest X-ray of myxomas appeared to be more and the delay to diagnosis was for small than for large Table of clinical features to myxoma size was significantly with neurologic symptoms, embolic and cardiac auscultation there was no significant between and or X-ray signs or symptoms; discovery; or delay in diagnosis (Table of clinical features to myxoma surface course All patients had patients during the 1 patient in during a second surgical for a of myxoma years after the first surgical a on in with cardiac and on the second postoperative from a in from mitral by a mitral and a in from meningitis with the the incidental tumor had been 1 patient a mitral valve endocarditis was with the myxoma. The most frequent postoperative was transient or atrial in patients A permanent cardiac for was for only 2 patients. Follow-up the postoperative patients were to patients to and not our Among the other patients, 4 and were during the follow-up Patients presented with peripheral fully The follow-up for patients with multiple cerebral is 14 years a In the present series, were for a median of 3 years 1 yr). Six patients had a of myxoma. Three patients with myxoma in the left and 17 years Three other patients had One of them suffered 2 in the left 16 and months The other 2 patients with had an initial myxoma in the right for 1 of them the was in the left atrium 3 years and for the other the were multiple in the left atrium and years and then in the right atrium years We report here the series of patients with left atrial myxoma diagnosed in a to our The patients presented over a 40-year ratio is with other in this ratio from to Myxomas can occur in all but are most frequent between the and of occur in although there is no for this female due in to In our series, younger age is significantly with neurologic signs or cardiac auscultation and is with neurologic or embolic symptoms in men and systemic symptoms in Clinical features The clinical features of these are by and there are no signs and symptoms that the of a myxoma In a of there are no symptoms at all in our there is no significant between the size of the tumor or 5 and the of discovery or atrial myxomas when the mitral or systemic 1) symptoms occur in of patients in our cases as mitral valve in mitral atrial and of fever are only of patients had in our study. Cardiac obstruction can be by progressive congestive cardiac failure on or or by syncope, or to mitral valve obstruction by the myxoma or coronary arteries The of obstruction may vary with body and these postural changes are particularly of myxoma (35,47). Cardiac failure the most frequent in our In our the of cardiac signs increased the diagnosis to that clinical symptoms are by another more common disease due to 2) emboli are the second of the classic in of myxoma patients in our study. than of emboli to the central nervous system in our but any may be to a of symptoms and cases emboli in the upper and lower coronary and more emboli may to aneurysms, as of cardiac myxomas as in 3 patients in our was 12, yr, We that the of an or surface is significantly with cerebral and peripheral 3) Constitutional signs are the of the classic these symptoms are may occur in to of cases The is lower in our series studied a at a cardiovascular These signs and symptoms myalgia, muscle weakness, arthralgia, fever, weight loss, and are obviously nonspecific and may occur in a of or or immunologic diseases tissue manifestations have also been reported in myxoma patients Cardiac auscultation Cardiac auscultatory may vary between and may on body presystolic or diastolic murmurs, significant mitral may be heard in more than of the patients in our The auscultatory of myxoma is “tumor is a heart sound of heard after the second heart sound may be with a heart sound or a mitral The tumor plop is in only of patients in our We established a significant between cardiac auscultation abnormalities and cardiac or systemic symptoms. and are abnormal in only of the patients those with systemic symptoms significant was in our The main but nonspecific laboratory abnormalities are and elevated or is or may occur by on the has also been common are and that the and of a by the tumor may be for systemic and manifestations has been with of in patients with myxoma that to after surgical removal A between the size of the tumor and the of has also been suggested have also been in myxoma tissue myxoma tissue in cases by and are nonspecific but observed in our atrial in of patients, the alterations by the is (less than of cases) in to the in mitral valve We observed a significant between signs and the of cardiac or systemic symptoms. also nonspecific features in the patients and are not for when the tumor is in our a left atrium enlargement and signs of pulmonary may be In our series, chest X-ray abnormalities were significantly with cardiac or systemic symptoms, but there were radiologic signs when the myxoma was by embolic or neurologic In cardiac signs or symptoms are more prevalent with large and may that embolic becoming are diagnosed before the the size 5 that to cardiac and radiologic data a positive between small tumor size and embolic Table 6). methods is the and diagnostic of is and not any risk of tumor and and cardiac examination may be by the echocardiography is less with an to but echocardiography the for surgery is only on echocardiographic evidence of the in our series angiocardiography has not been since coronary in patients over 40 years old is in to coronary disease Other diagnostic methods and The of and over echocardiography is that of and thoracic are also more in tumor and tumor and size data that most left atrial myxomas arise from the atrial or the on the of and on the appearance is or with a or or is and the surface is either or and in our myxomas with constitutional symptoms, or In the such as and surface are seen in older that In our series, there was no significant between and The size and weight of myxomas but in our the of symptoms was in patients with on could or myxomas and or myxomas according to the of the that all occurred in patients with and myxomas. the of cardiac myxomas have been The of most is that myxomas are of is no that myxomas are myxomas may have a of that at first may be the of multiple surface or is not with or any of presentation, and is important not to an on the basis of these atypical are cardiac not be with myxomas The to the tumor are to be and analysis has that myxoma as tumor = and are and may be for and cases with is as is the showed that was by is also a for the that myxomas arise from the to A study that myxomas with a between tumor size and the of this a in Myxomas may to the but these not have any The myxoma tissue emboli may may the and may or may but any cerebral tissue years the may to Three patients in our series had embolic that into the with of multiple aneurysms, any or during and follow-up The of for myxomas is surgical removal the diagnosis is of the tumor is Embolic complications or are in patients: of patients in the time of our series, not due to cardiac but 2 patients had cardiac arrest in the before surgery with successful resuscitation. surgery is a as most are can be The may according to In our series, was 3 patients during the postoperative period before and another patient in of meningitis not to myxoma. The most frequent postoperative was transient or with an of Cardiac myxomas occur but or cases have been The reported rate ranges from to in the in our are reported from as as a months to as as years after of the myxoma in our The of is not but risk or of tumor of the a of tumor in the In most cases of of the to be the of Patients with abnormalities are at risk of and from 2 or more of the cardiac and myxomas or of the with and are as or The risk of for and myxomas is about and is only for In our series, 3 cases the cardiac myxoma the time of myxoma patients are younger than myxoma patients. myxomas of the 2 patient groups are not A to has been identified The is In the the rate is and after of myxomas ranges from 0 to in our may surgical removal in our A patients may permanent cardiac for conduction 2 patients in our In of the of a tumor that with mitral valve to in heart failure, the mitral valve is In our only 1 patient mitral valve for endocarditis with left atrial myxoma. the myxoma patients to be and cases. echocardiogram is over the period at diagnosis The mitral valve other and heart more common than and occur in patients with myocardial infarction or systemic symptoms are present (fever, weight loss, the diagnosis heart and tissue disease or The of embolic and constitutional symptoms is due more to but may also myxoma. The of or syndrome to the 2 diseases, as these are in myxoma. myxomas are occasionally the clinical of myxoma and endocarditis more of cardiac myxomas reported 40 cases with a presentation similar to is no clinical between and noninfected myxoma cardiac symptoms and the rate of systemic or cerebral constitutional symptoms significantly in patients with myxoma (fever, elevated and men are more than series of 112 cases of left atrial myxoma clinical that this tumor may a of clinical symptoms not only such as cardiac but also or neurologic is made only on clinical there are no signs or symptoms. but or cases have been that and of the by the tumor may be for or including the is the of for diagnosis and follow-up of this myxomas are be in the diagnosis of mitral valve disease and congestive heart failure, in patients with is also for any patient with embolic embolic in in the of signs or symptoms of endocarditis or to a of myxoma as the embolic The obtained by be are to the clinical features of in in myxoma or be studied for embolic myxomas with of could be performed to for the ratio and age We a series of 112 cases of left atrial myxoma diagnosed in a French and 40 age range, yr) over 40 years, from 1959 to Symptoms of mitral valve the first of the classic of myxoma presentation, were present in 75 patients with cardiac failure or Symptoms of the second frequent presentation in the classic were observed in 33 cases with 1 or several cerebral emboli with are at risk than females of embolic The of the classic of constitutional symptoms with fever, weight loss, or symptoms tissue due to and patients have more neurologic symptoms, and female patients have more systemic symptoms. patients (64%) had cardiac auscultation valve disease and more the tumor plop The most frequent was left atrial were The number of myxoma patients diagnosed after 1977 the introduction of echocardiography as a noninvasive diagnostic there was no significant in the time from onset of symptoms to between patients seen in the before and after The tumor from 1 to 15 cm with a weight of between 15 and The myxoma surface was or in of the and in the other cases. Myxomas in patients with embolism have a those in patients with cardiac symptoms, auscultation signs, tumor and electrocardiogram or radiologic signs of left atrium and are significantly the The is and only 4 occurred our 112 cases over a median follow-up of 3 The rate is but follow-up and echocardiography are for patients. The surgical were performed during the 40-year period by We are to for the

Medicine · review · 878 citationsread the source →

The pleasure of art as a matter of fact

You have accessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Nadal Marcos and Skov Martin 2018The pleasure of art as a matter of factProc. R. Soc. B.2852017225220172252http://doi.org/10.1098/rspb.2017.2252SectionYou have accessCommentThe pleasure of art as a matter of fact Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed Search for more papers by this author and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Search for more papers by this author Marcos Nadal Marcos Nadal http://orcid.org/0000-0002-9341-4688 Department of Psychology, University of the Balearic Islands, Palma de Mallorca 07122, Spain [email protected] Google Scholar Find this author on PubMed and Martin Skov Martin Skov Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Copenhagen 2650, Denmark Center for Decision Neuroscience, Copenhagen Business School, Copenhagen 2000, Denmark Google Scholar Find this author on PubMed Published:21 March 2018https://doi.org/10.1098/rspb.2017.2252All other forms of perception divide a man, because they are exclusively based either on the sensuous or on the intellectual part of his being; only the perception of the Beautiful makes something whole of him, because both his natures must accord with it.— Schiller, 1793–1795, Letters on the Aesthetic Education of Man, p. 138, Letter 27Can art make us better people? Better members of society? In her recent article, 'Pleasure junkies all around! Why it matters and why "the arts" might be the answer: a biopsychological perspective', Christensen [1] claims that engaging with art can promote healthy choices, choices that balance short-term pleasure goals with long-term general well-being. She suggests that many modern life conveniences, such as social media, computer games or online shopping, have the potential to turn us into 'pleasure junkies' because they maximize short-term pleasures. But art, Christensen argues, is a safe choice and a means to remedy this unhealthy addiction to pleasure. Christensen's argument is grounded on three claims about the sort of pleasure we get from art. First, in contrast to low-level pleasure, which Christensen conceives as 'a mere perceptual stimulation leading to a rewarding sensation (food, sex, etc.)' ([1], p. 2), pleasure from art is presented as a kind of higher-order pleasure that engages 'broader neural networks implied in the attribution of meaning' (p. 2), presumably leading to 'long-term maintenance of healthy bodily function' (p. 2). Second, 'the arts do not induce states of craving without fulfilment—as do activities with reinforcement schedules which are prone to create habits and addictions such as intermittent variable ratio or interval reinforcement schedules (e.g. social media, gambling, football, extreme sports, drugs' (p. 4). Third, 'the arts do not search for a perceptual "Bliss point" […]. They do not just repeat over and over again a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch" (e.g. sugar, sexualized body displays, certain musical lyrics, tones; i.e. a perceptual "bliss point")' (p. 4).The claim, in a nutshell, is that the pleasure induced by art is different to the pleasure induced by food, sex, sports or drugs, because it is related to the balanced activation of brain systems related to short-term pleasure and long-term wellbeing goals, because it does not induce craving, and because it is not aimed at a perceptual 'bliss point'. This distinct sort of pleasure, according to Christensen, makes it possible for the arts to thwart the pernicious effects that the unhealthy urges and cravings licensed by 'today's mainstream acceptance of pleasure-seeking behaviour' (p. 5) have on individuals' lives and on societies. Such sweeping statements about art, food, sex, sports and society as a whole merit close examination. Christensen's primary claim that the pleasure induced by art is of a special kind, different to the pleasure induced by other activities is not supported by current understanding of what pleasure is. It is, moreover, contradicted by abundant empirical evidence. This evidence shows that pleasures, whatever their source, owe to activity in the same mesocorticolimbic circuit [2] and are encoded as a common neural currency [3]. As Kent Berridge and Morten Kringelbach put it: 'the brain mechanisms involved in fundamental pleasures (food and sexual pleasures) overlap with those for higher-order pleasures (e.g. monetary, artistic, musical, altruistic and transcendent pleasures) […] From sensory pleasures and drugs of abuse […] to monetary, aesthetic and musical delights, all pleasures seem to involve the same hedonic brain systems' ([4], p. 481). Thus, there is no evidence for specific brain regions or neural circuits related to the pleasure from art. Rather, the appreciation of art relies on brain mechanisms that evolved to appraise the value of biologically relevant objects in relation to internal homeostatic states [5]: 'Emotional reactions to music, further, activate the same cortical, subcortical and autonomic circuits, which are considered as the essential survival circuits of biological organisms in general' ([6], p. 6). In sum, the evidence shows that pleasure elicited by music and other art forms is no different in genesis and function to the pleasure induced by food, drugs and sex [7,8]. This is a matter of fact, not opinion. What supports Christensen's argument if not empirical evidence? In our view, her argument for the distinctness of art-induced pleasure seems based upon an oversimplified and devaluing conception of the pleasures of sex, food and sports, and a very narrow notion of art and its function. Christensen presents food, sex and sports as meaningless low-level sources of pleasure, and the arts as privileged vehicles for meaningful experiences. It is the personal and meaningful engagement with art—Christensen suggests—that fosters a balanced activation of brain systems related to short-term pleasure and long-term well-being goals. However, rarely—if ever—are food, sex and sports meaningless rewarding sensations. Contrary to Christensen's definition on page 2 of her article, pleasure—even sensory pleasure—is not simply reward, and never simply a sensation [4]. Indulging in food, sex or sports are meaningful and personally significant experiences that are not a matter of mere physical sensation. The experience of pleasure from food and sex is shaped by context, knowledge, expectations, anticipations, attitudes and beliefs that bring meaning to them [9–11]. Sex can be meaningful because it signifies physical connection with one's loved one, because it is cheating on someone, or deemed a sin. Likewise, eating is not about obtaining low-level pleasure. What we eat, the way we eat, what we believe about what we eat, where and whom we eat with, imbue eating with individual and social meaning, and shape the actual pleasure of eating [12]. On the other hand, encounters with art are not necessarily meaningful [13,14]. Actually, there is nothing intrinsically meaningful about engaging with art. Many laypeople lack the knowledge schemata required to engage meaningfully with abstract, cubist or contemporary art [15,16]. There are plenty of artworks people do not find meaningful or pleasant. Meaning making is not a special feature of art; it is a general feature of our species's cognition [17,18]. We can endow virtually any aspect of reality with meaning: sex, food, sports, a urinal, the shape of a cloud, an averted glance, someone's absence. Christensen's argument also rests on a historically and culturally narrow conception of art and its function. Art is presented as a circumscribed category of activities that elicit a unique sort of pleasant experiences: — The arts are set of activities of a special kind that share certain defining features distinguishing them from other activities: 'the arts push boundaries, surprise, reveal and excite both artist and spectator' ([1], p. 4).— Art encounters are positive, leading to 'pleasurable chills' and pleasurable experiences of understanding: 'The moment of meaning-assignation, also called "mastering" or "understanding" an artwork, is therefore a pleasurable experience' ([1], p. 4).— The pleasure elicited by art is special, because it does not involve craving for intense peaks: 'The arts do not search for a perceptual "bliss point" […] They do not just repeat over and over a sensory stimulus that excites the senses and induces craving for more of a "pleasurable itch"' ([1], p. 4).This characterization of the arts substantially overlaps with the notion of 'fine arts'. The core features of this characterization were instituted in the eighteenth century, after European intellectuals grouped certain activities into a distinct and autonomous collection, labelled 'fine arts'. To make sense of and promote this grouping, it became imperative to identify a common essence setting art apart from other activities [19,20,21]. One of the most popular proposals was that only art could produce a special sort of pleasure, sophisticated and polite [19,21]—a conception stemming not from any understanding of physiology, but from mere speculation. This limited historical and cultural scope renders this conception of the arts unfit for behavioural or neuroscientific research [19]. The category 'the arts' should not be mistaken for a natural kind. It is a historical convention, and has no direct biological correspondence. Moreover, this conception of art that Christensen espouses does not apply to art as practised in non-Western societies [19,22]. It does not even apply to Western art before the eighteenth century or after the nineteenth century [19,20,21]. First, art does not necessarily evoke pleasurable experiences. There are abundant artworks intended to arouse negative emotions [19,23], and to portray physical and moral ugliness [24]. Understanding art is not necessarily a pleasant experience: it can be an angering, disgusting or upsetting one [25]. Second, many artworks actually exploit repetition, bliss points and craving [26]. Repetition is a fundamental design feature of music and other performance arts [27]: In Relation in Space (1976) Marina Abramovic and Ulay ran into each other repeatedly for an hour; Ravel's Bolero is a 17 min-long instance of melodic and rhythmic repetitiveness. Anticipation and craving for bliss points are also essential to music [28]. In fact, the enjoyment of music is linked to intense feelings of anticipation and expectation caused by dopamine activity in the caudate nucleus (also involved in the rewarding aspect of food) [29,30], and peak pleasure states (bliss points) [31], caused by the release of dopamine and opioids in the brain's reward system (also involved in cocaine induced euphoria) [29,30]. Given the available evidence, therefore, there is no reason to believe that the pleasure from art is special or unique [32].In sum, Christensen's claim for the distinctiveness of pleasure from art is contradicted by empirical evidence, and her argument for the beneficial effects of art rests upon disputed foundations. Art's capacity to promote healthier choices and make us better people that can contribute to a better society remains as unconfirmed today as it was when Schiller speculated on art's power to harmonize human's conflicting sensuous and formal impulses. Christensen's argument is problematic even if intended to highlight hypothetical possibilities. Arguments about hypothetical possibilities should still rely on valid premises, and scientific hypotheses should be grounded on evidence, or at least in line with it. Otherwise, they are merely unfounded speculations. Scientific aesthetics is only just finding its footing and its place within cognitive neuroscience [33,34]. If evidence is ignored or rejected because it does not fit preconceived notions about art and its function, scientific aesthetics will become only an arena to promote and legitimize personally appealing notions of art by applying a scientific gloss over them. A proper scientific study of art needs to be grounded on empirical evidence and strong arguments that follow from solid premises [35,36]. 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(doi:10.1016/j.plrev.2017.06.013) PubMed, ISI, Google Scholar Previous ArticleNext Article VIEW FULL TEXT DOWNLOAD PDF FiguresRelatedReferencesDetailsCited by Clemente A, Pearce M, Skov M and Nadal M (2021) Evaluative judgment across domains: Liking balance, contour, symmetry and complexity in melodies and visual designs, Brain and Cognition, 10.1016/j.bandc.2021.105729, 151, (105729), Online publication date: 1-Jul-2021. Chuan-Peng H, Huang Y, Eickhoff S, Peng K and Sui J (2020) Seeking the "Beauty Center" in the Brain: A Meta-Analysis of fMRI Studies of Beautiful Human Faces and Visual Art, Cognitive, Affective, & Behavioral Neuroscience, 10.3758/s13415-020-00827-z, 20:6, (1200-1215), Online publication date: 1-Dec-2020. Skov M and Nadal M (2020) A Farewell to Art: Aesthetics as a Topic in Psychology and Neuroscience, Perspectives on Psychological Science, 10.1177/1745691619897963, 15:3, (630-642), Online publication date: 1-May-2020. Kalpokas I (2019) Making the Theory Political A Political Theory of Post-Truth, 10.1007/978-3-319-97713-3_4, (87-121), . Kalpokas I (2019) Affective Encounters of the Algorithmic Kind: Post-Truth and Posthuman Pleasure, Social Media + Society, 10.1177/2056305119845678, 5:2, (205630511984567), Online publication date: 1-Apr-2019. Skov M (2019) Aesthetic Appreciation: The View From Neuroimaging, Empirical Studies of the Arts, 10.1177/0276237419839257, 37:2, Online publication date: H, I and (2020) A for We Aesthetic in Human Neuroscience, A and in A New for Arts, This March Article in 2018 The Author(s)Published by the Royal Society. All rights Citations and are available with

Proceedings of the Royal Society B Biological Sciences · editorial or comment · 24 citationsread the source →

Intergenerational transmission of child maltreatment in South Australia, 1986-2017: a retrospective cohort study.

Background: The extent of intergenerational transmission of child maltreatment is unclear due to methodological limitations in previous studies. In this study, we aimed to examine factors associated with intergenerational transmission of child maltreatment and quantify its extent in a population sample over a 30-year period in South Australia. Methods: In this retrospective cohort study, we used linked administrative data from the South Australian Birth Registry to identify dyads of mothers and their children both born in South Australia between July 1, 1986, and June 30, 2017. Three child protection system (CPS) outcomes (any CPS involvement, substantiated maltreatment, and time spent in out-of-home care) were computed from data obtained from the South Australian Department for Child Protection. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for child CPS outcomes according to their mother's CPS exposure. Findings: 38 556 unique mother-child dyads were included. 458 (2·0%) of 23 437 children whose mothers had no CPS involvement in childhood had a substantiated report of maltreatment and 127 (0·5%) spent time in out-of-home care. By comparison, 970 (22·1%) of 4382 children whose mothers experienced substantiated maltreatment in childhood had substantiated maltreatment and 469 (10·7%) spent time in out-of-home care. After adjusting for potential confounders, children of mothers with any CPS involvement in childhood had an increased risk of CPS contact compared with children whose mothers had no CPS involvement; this risk was greatest for children of mothers who had both substantiated maltreatment and spent time in out-of-home care (HR 6·25 [95% CI 5·59-6·98] for any CPS involvement, 13·69 [10·08-16·92] for substantiated maltreatment, and 25·78 [18·23-36·45] for any time in out-of-home care). Risks of child CPS outcomes were substantially increased for children of mothers who had a first CPS notification under the age of 1 year or who had any CPS notification at age 13-17 years. Interpretation: Children are at high risk of maltreatment if their mother experienced maltreatment as a child. Assisting survivors of childhood maltreatment, particularly female survivors, provides a crucial intervention opportunity to help prevent further child abuse and neglect. Funding: Australian National Health and Medical Research Council; Channel 7 Children's Research Foundation.

The Lancet. Public health · 31 citationsread the source →

Predictors of treatment resistance in patients with schizophrenia: a population-based cohort study.

Background: Identification of patients at high risk of treatment-resistant schizophrenia at the time of schizophrenia diagnosis would be of great clinical benefit in minimising the delay to clozapine treatment in patients unlikely to respond to non-clozapine antipsychotics. However, little is known about predictors of treatment resistance in this patient population. We used a treatment-based proxy for treatment-resistant schizophrenia to identify candidate predictors of treatment resistance at first hospital contact with a schizophrenia diagnosis. Methods: In this population-based cohort study, we obtained Danish national registry data for all adult patients (≥18 years) with incident schizophrenia diagnosed between Jan 1, 1996, and Dec 31, 2006, and followed up until Dec 31, 2010. Our main proxy definition of treatment-resistant schizophrenia was the earliest instance of either clozapine initiation or hospital admission for schizophrenia after having had two periods of different antipsychotic monotherapy. We did multivariable Cox proportional hazards regression analysis to estimate the association between baseline candidate predictors and treatment resistance. Findings: 8624 patients fulfilled the criteria for inclusion. In multivariable complete-case analyses, 1703 (21%) of 8044 patients fulfilled the main proxy definition of treatment-resistant schizophrenia during a median follow-up of 9·1 years (IQR 6·3-11·9). Younger age (hazard ratio 0·96 [95% CI 0·95-0·97]), living in a less urban area (provincial 1·38 [1·23-1·56], rural 1·44 [1·25-1·65]), primary education level (0·88 [0·79-0·98]), more than 30 bed-days in psychiatric hospital in the year before first schizophrenia diagnosis (1·54 [1·35-1·75]), inpatient at first schizophrenia diagnosis (2·07 [1·87-2·29]), paranoid subtype (1·24 [1·13-1·37]), comorbid personality disorder (1·24 [1·11-1·39]), psychotropic drug use (antipsychotics 1·51 [1·35-1·69], antidepressants 1·15 [1·03-1·29], and benzodiazepines 1·22 [1·10-1·37]), and previous suicide attempt (1·21 [1·07-1·39]) were all significantly associated with treatment-resistant schizophrenia. Interpretation: Our study identifies several candidate predictors that could potentially be included in future prediction models for treatment-resistant schizophrenia. Notably, established risk factors for schizophrenia did not predict treatment resistance, suggesting that treatment-resistant disease might be a distinct subtype of schizophrenia and not merely a more severe form. Funding: European Community's Seventh Framework Programme.

The lancet. Psychiatry · 127 citationsread the source →

Social inequalities in multimorbidity, frailty, disability, and transitions to mortality: a 24-year follow-up of the Whitehall II cohort study.

Background: Social inequalities in mortality persist in high-income countries with universal health care, and the mechanisms by which these inequalities are generated remain unclear. We aimed to examine whether social inequalities were present before or after the onset of adverse health conditions (multimorbidity, frailty, and disability). Methods: Our analysis was based on data from the ongoing Whitehall II cohort study, which enrolled British civil servants aged 35-55 years in 1985-88. Participants were assessed for three indicators of socioeconomic status (education, occupational position, and literacy) at age 50 years. Participants underwent clinical examinations (in 2002-04, 2007-09, 2012-13, and 2015-16) for assessment of frailty (two or more of low physical activity, slow walking speed, poor grip strength, weight loss, and exhaustion) and disability (two or more difficulties in bathing, dressing, going to the toilet, transferring, feeding, and walking). In addition, electronic health records were used to assess the incidence of multimorbidity (two or more of diabetes, coronary heart disease, stroke, chronic obstructive pulmonary disease, depression, arthritis, cancer, dementia, and Parkinson's disease) and mortality. In analyses adjusted for sociodemographic factors, we used multistate models to examine social inequalities in transitions from healthy state to adverse health conditions and subsequently to mortality. Findings: Of 10 308 individuals in the Whitehall II study cohort, 6425 had relevant data available at 50 years and to the end of follow-up on Aug 31, 2017, and were included in our analysis. Participants were followed up for a median of 23·6 years (IQR 19·6-28·9). 1694 (26·4%) of 6425 participants developed multimorbidity, 1733 (27·0%) became frail, 692 (10·8%) had a disability, and 611 (9·5%) died. Multimorbidity (hazard ratio [HR] 4·12 [95% CI 3·41-4·98]), frailty (HR 2·38 [95% CI 1·93-2·93]), and disability (HR 1·73 [95% CI 1·34-2·22]) were associated with increased risk of mortality; these associations were not modified by socioeconomic status. In multistate models, occupation was the socioeconomic status indicator that was most strongly associated with inequalities in the transition from healthy state to multimorbidity (HR 1·54 [95% CI 1·37-1·73]), to frailty (HR 2·08 [95% CI 1·85-2·33]), and to disability (HR 1·44 [95% CI 1·18-1·74]). Socioeconomic status indicators did not affect transitions to mortality in those with multimorbidity, frailty, or disability. Interpretation: Socioeconomic status affects the risk of multimorbidity, frailty, and disability, but does not affect the risk of mortality after the onset of these adverse health conditions. Therefore, primary prevention is key to reducing social inequalities in mortality. Of the three adverse health conditions, multimorbidity had the strongest association with mortality, making it a central target for improving population health. Funding: UK Medical Research Council; National Institute on Aging, National Institutes of Health; British Heart Foundation.

The Lancet. Public health · 239 citationsread the source →

Surgical and psychosocial outcomes in the rural injured--a follow-up study of the 2001 earthquake victims.

Introduction: After a major disaster in a developing country, the graphic media coverage of the dead and injured invariably leads to an influx of volunteering healthcare personnel to the disaster zone. Very few studies document the outcomes of the treatment rendered in this field setting, under compromised conditions. We revisited the rural victims of the 2001 Gujarat earthquake in an attempt to analyse their surgical outcome and the status of their physical/psychosocial rehabilitation, 2 years after the disaster. Method: We traced displaced victims treated for earthquake-related injuries to their new homes. A community health worker interviewed patients with an oral questionnaire in the local language about injuries, the examining physician and first aid, orthopaedic implants, amputations, wounds, disability, deformity, residual pain, occupational and economic rehabilitation, post traumatic stress disorder (PTSD) and perceptions of healthcare rendered. Results: We located 133 of the 179 non-urban victims, from 11 villages. There were 10% missed injuries, 19% infection rate, restricted range of motion in 12%, non-union rate in 23% and reoperations in 30.5% patients. Fifty-one percent had resumed their previous occupation, but only 30% had recovered economically. Of 98% who had destroyed homes, 89% had their homes rebuilt. Residual sadness was the only significant PTSD symptom. Conclusion: This trauma outcome study highlights the shortcomings of surgeons for disaster-related work. One-tenth of the injuries were missed, suggesting that field examination at the site of disaster was more difficult than in the comfort of the hospital emergency room. Further there were inappropriately timed, aggressive implant operations, short time commitments, a lack of follow-up and a high rate of reoperations contributing to subsequent morbidity. These pointed to a need for training in disaster medicine within the curriculum of surgical residency. On the brighter side, despite poor sterility, prolonged transport times and no prehospital care, the postoperative infection rate was lower than expected. This perhaps was due to use of potent antibiotics in a previously unexposed rural population. Good physiotherapy given in the temporary shelters, by the informal carers within the family and by voluntary groups, kept up a good range of motion and reduced the final disability. PTSD was marked 3-6 months after the event, but was minimal 2 years postquake. Sadness about the event was the only residual PTSD symptom. While there were varying perceptions of satisfactory outcome, we found good coping mechanisms in place. The simple village folks were largely happy to be alive and accepted the residual deformities and cosmetic blemishes as a "small price to pay".

Injury · 40 citationsread the source →

PTSD in urban primary care: high prevalence and low physician recognition.

Background: Posttraumatic stress disorder (PTSD) is associated with medical and psychological morbidity. The prevalence of PTSD in urban primary care has not been well described. Objective: To measure the prevalence of PTSD in primary care patients overall and among those with selected conditions (chronic pain, depression, anxiety, heavy drinking, substance dependence (SD), irritable bowel syndrome (IBS), and immigrant status). Design: Cross-sectional study. Participants: English-speaking patients aged 18-65 years old, awaiting primary care appointments in an urban academic medical center, were eligible for enrollment to determine PTSD prevalence (N = 509). Additional eligible participants (n = 98) with IBS or SD were subsequently enrolled. Measurements: PTSD (past year) and trauma exposure were measured with Composite International Diagnostic Interview. We calculated the prevalence of PTSD associated with depression, anxiety, heavy drinking, SD, IBS, and chronic pain. Only the analyses on heavy drinking, SD, and IBS used all 607 participants. Results: Among the 509 adults in primary care, 23% (95% CI, 19-26%) had PTSD, of whom 11% had it noted in the medical record. The prevalence of PTSD, adjusted for age, gender, race, and marital and socioeconomic statuses, was higher in participants with, compared to those without, the following conditions: chronic pain (23 vs 12%, p = .003), major depression (35 vs 11%, p < .0001), anxiety disorders (42 vs 14%, p < .0001), and IBS (34 vs 18%, p = .01) and lower in immigrants (13 vs 21%, p = .05). Conclusions: The prevalence of PTSD in the urban primary care setting, and particularly among certain high-risk conditions, compels a critical examination of optimal approaches for screening, intervention, and referral to PTSD treatment.

Journal of general internal medicine · 148 citationsread the source →

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

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

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