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المكتبة البحثية23 results
Peer-reviewed works with DOI and abstract, discovered from MEDLINE-indexed literature. Candidates: no tier, no stated finding, not yet read.
Rapee RM, Shaw T, Hunt C, Bussey K, Hudson JL, Mihalopoulos C, Roberts C, Fitzpatrick S, Radom N, Cordin T, Epstein M, Cross D. (2020)MEDLINE-indexed journal, not yet read by usAggressive behavior · randomised controlled trial Combining whole-school and targeted programs for the reduction of bullying victimization: A randomized, effectiveness trial.
Despite the extensive evaluation of school-based interventions for bullying, victimization remains a significant problem in schools. Bullying victimization is significantly predicted by contextual (school-related) factors. As a consequence whole-school programs have been commonly used to prevent and reduce bullying victimization. Evidence also points to individual risk factors (such as emotional distress) in predicting victimization, yet programs to prevent bullying victimization by changing these individual risks are far less developed. Few studies have approximated "real-world" implementation conditions in their trials. The current effectiveness trial evaluated the combination of a whole-school program designed to prevent bullying perpetration and victimization together with a targeted intervention for at-risk students, teaching them individual and dyadic strategies to reduce their anxiety and manage victimization, allowing schools some latitude to implement programs as they typically would. Students from Grades 3 and 4 (N = 8,732) across 135 schools were randomly assigned to one of four conditions: combined intervention; whole-school intervention only; individual intervention only; and care as usual. Victimization decreased significantly and similarly across all four conditions at 12 and 24 months following baseline. Similar reductions and failure to discriminate conditions were found on other key constructs: anxiety; bullying perpetration; and depression. Possible reasons for the failure to demonstrate victimization prevention differences and lessons learned from this large, effectiveness trial are considered.
Aggressive behavior · randomised controlled trial · 15 citationsread the source →
Development and validation of the Body and Appearance Self-Conscious Emotions Scale (BASES).
The purpose of these studies was to develop a psychometrically sound measure of shame, guilt, authentic pride, and hubristic pride for use in body and appearance contexts. In Study 1, 41 potential items were developed and assessed for item quality and comprehension. In Study 2, a panel of experts (N=8; M=11, SD=6.5 years of experience) reviewed the scale and items for evidence of content validity. Participants in Study 3 (n=135 males, n=300 females) completed the BASES and various body image, personality, and emotion scales. A separate sample (n=155; 35.5% male) in Study 3 completed the BASES twice using a two-week time interval. The BASES subscale scores demonstrated evidence for internal consistency, item-total correlations, concurrent, convergent, incremental, and discriminant validity, and 2-week test-retest reliability. The 4-factor solution was a good fit in confirmatory factor analysis, reflecting body-related shame, guilt, authentic and hubristic pride subscales of the BASES. The development and validation of the BASES may help advance body image and self-conscious emotion research by providing a foundation to examine the unique antecedents and outcomes of these specific emotional experiences.
Body image · cohort or longitudinal · 74 citationsread the source →
Effect of treating depression on quality-of-life and exercise tolerance in severe COPD.
The aim of this study was to determine whether treating concomitant depression improves quality of life and exercise tolerance in COPD patients. Out-patients with moderate to severe, stable COPD completed Hospital Anxiety-Depression (HAD) and General Health questionnaires. A psychiatrist interviewed those with high scores. In a randomised, double-blind fashion, 28 depressed COPD patients took a selective serotonin re-uptake inhibitor, Paroxetine 20 mg daily, or matched placebo for 6 weeks. Subsequently, all patients took un-blinded Paroxetine for 3 months. From these questionnaires, 35% of 135 patients had significant depression, but this was confirmed by psychiatric interview in only 21%. Throughout the study, there were no changes in laboratory lung function nor in home peak flow. Six weeks' treatment produced no significant differences between placebo and treatment group in either depression, quality of life scores or 6-minute walking distances, although overall improvements in depression, correlated with increases in walking distance. Three months of un-blinded treatment, significantly improved depression scores (self-complete HAD, Beck's Depression and psychiatrist-completed Montgomery-Asberg scores), walking distances (369 to 427 m, p = 0.0003) and St. George's Respiratory Questionnaire Total Scores (65 to 58, p = 0.033). Although self-complete questionnaires over-diagnose depression, the condition is nevertheless common in patients with moderately severe COPD. Six weeks of antidepressants is insufficient to improve either depression, quality of life or exercise tolerance. However, our study suggests that a longer course of treatment may be effective and that improvements in depression are associated with improvements in exercise tolerance. A larger, double blind study with a longer treatment period is indicated.
COPD · randomised controlled trial · 67 citationsread the source →
Exercise training undertaken by people within 12 months of lung resection for non-small cell lung cancer.
Background: Decreased exercise capacity and health-related quality of life (HRQoL) are common in people following lung resection for non-small cell lung cancer (NSCLC). Exercise training has been demonstrated to confer gains in exercise capacity and HRQoL for people with a range of chronic conditions, including chronic obstructive pulmonary disease and heart failure, as well as in people with prostate and breast cancer. A programme of exercise training may also confer gains in these outcomes for people following lung resection for NSCLC. This systematic review updates our 2013 systematic review.
Objectives: The primary aim of this review was to determine the effects of exercise training on exercise capacity and adverse events in people following lung resection (with or without chemotherapy) for NSCLC. The secondary aims were to determine the effects of exercise training on other outcomes such as HRQoL, force-generating capacity of peripheral muscles, pressure-generating capacity of the respiratory muscles, dyspnoea and fatigue, feelings of anxiety and depression, lung function, and mortality.
Search methods: We searched for additional randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 2 of 12), MEDLINE (via PubMed) (2013 to February 2019), Embase (via Ovid) (2013 to February 2019), SciELO (The Scientific Electronic Library Online) (2013 to February 2019), and PEDro (Physiotherapy Evidence Database) (2013 to February 2019).
Selection criteria: We included RCTs in which participants with NSCLC who underwent lung resection were allocated to receive either exercise training, which included aerobic exercise, resistance exercise, or a combination of both, or no exercise training.
Data collection and analysis: Two review authors screened the studies and identified those eligible for inclusion. We used either postintervention values (with their respective standard deviation (SD)) or mean changes (with their respective SD) in the meta-analyses that reported results as mean difference (MD). In meta-analyses that reported results as standardised mean difference (SMD), we placed studies that reported postintervention values and those that reported mean changes in separate subgroups. We assessed the certainty of evidence for each outcome by downgrading or upgrading the evidence according to GRADE criteria.
Main results: Along with the three RCTs included in the original version of this review (2013), we identified an additional five RCTs in this update, resulting in a total of eight RCTs involving 450 participants (180 (40%) females). The risk of selection bias in the included studies was low and the risk of performance bias high. Six studies explored the effects of combined aerobic and resistance training; one explored the effects of combined aerobic and inspiratory muscle training; and one explored the effects of combined aerobic, resistance, inspiratory muscle training and balance training. On completion of the intervention period, compared to the control group, exercise capacity expressed as the peak rate of oxygen uptake (VO2peak) and six-minute walk distance (6MWD) was greater in the intervention group (VO2peak: MD 2.97 mL/kg/min, 95% confidence interval (CI) 1.93 to 4.02 mL/kg/min, 4 studies, 135 participants, moderate-certainty evidence; 6MWD: MD 57 m, 95% CI 34 to 80 m, 5 studies, 182 participants, high-certainty evidence). One adverse event (hip fracture) related to the intervention was reported in one of the included studies. The intervention group also achieved greater improvements in the physical component of general HRQoL (MD 5.0 points, 95% CI 2.3 to 7.7 points, 4 studies, 208 participants, low-certainty evidence); improved force-generating capacity of the quadriceps muscle (SMD 0.75, 95% CI 0.4 to 1.1, 4 studies, 133 participants, moderate-certainty evidence); and less dyspnoea (SMD -0.43, 95% CI -0.81 to -0.05, 3 studies, 110 participants, very low-certainty evidence). We observed uncertain effects on the mental component of general HRQoL, disease-specific HRQoL, handgrip force, fatigue, and lung function. There were insufficient data to comment on the effect of exercise training on maximal inspiratory and expiratory pressures and feelings of anxiety and depression. Mortality was not reported in the included studies.
Authors' conclusions: Exercise training increased exercise capacity and quadriceps muscle force of people following lung resection for NSCLC. Our findings also suggest improvements on the physical component score of general HRQoL and decreased dyspnoea. This systematic review emphasises the importance of exercise training as part of the postoperative management of people with NSCLC.
The Cochrane database of systematic reviews · meta-analysis · 76 citationsread the source →
The global burden of perinatal common mental health disorders and substance use among migrant women: a systematic review and meta-analysis.
Background: There are one billion migrants globally, of whom 82 million are forced migrants. Pregnant migrants face pre-migration stressors such as conflict, transit stressors including poverty, and post-migration stressors including navigating the immigration system; these stressors can make them vulnerable to mental illness. We aimed to assess the global prevalence of and risk factors for perinatal mental health disorders or substance use among women who are migrants.
Methods: In this systematic review and meta-analysis, we searched OVID MEDLINE, Embase, PsycINFO, CENTRAL, Global Health, Scopus, and Web of Science for studies published from database inception until July 8, 2022. Cohort, cross-sectional, and interventional studies with prevalence data for any mental illness in pregnancy or the postnatal period (ie, up to a year after delivery) or substance use in pregnancy were included. The primary outcome was the prevalence of perinatal common mental health disorders among women who are migrants, globally. Data for study quality and risk factors were also extracted. A random-effects meta-analysis was used to calculate pooled prevalence estimates, when appropriate. Sensitivity analyses were conducted according to study quality, sample representativeness, and method of outcome assessment. Risk factor data were synthesised narratively. This study is registered with PROSPERO, CRD42021226291.
Findings: 18 650 studies were retrieved, of which 135 studies comprising data from 621 995 participants met the inclusion criteria. 123 (91%) of 135 studies were conducted in high-income host countries. Five (4%) of 135 studies were interventional, 40 (30%) were cohort, and 90 (66%) were cross-sectional. The most common regions of origin of participants were South America, the Middle East, and north Africa. Only 26 studies presented disaggregated data for forced migrants or economic migrants. The pooled prevalence of perinatal depressive disorders was 24·2% (range 0·5-95·5%; I2 98·8%; τ2 0·01) among all women who are migrants, 32·5% (1·5-81·6; 98·7%; 0·01) among forced migrants, and 13·7% (4·7-35·1; 91·5%; 0·01) among economic migrants (p<0·001). The pooled prevalence of perinatal anxiety disorders was 19·6% (range 1·2-53·1; I2 96·8%; τ2 0·01) among all migrants. The pooled prevalence of perinatal post-traumatic stress disorder (PTSD) among all migrant women was 8·9% (range 3·2-33·3; I2 97·4%; τ2 0·18). The pooled prevalence of perinatal PTSD among forced migrants was 17·1% (range 6·5-44·3; I2 96·6%; τ2 0·32). Key risk factors for perinatal depression were being a recently arrived immigrant (ie, approximately within the past year), having poor social support, and having a poor relationship with one's partner.
Interpretation: One in four women who are migrants and who are pregnant or post partum experience perinatal depression, one in five perinatal anxiety, and one in 11 perinatal PTSD. The burden of perinatal mental illness appears higher among women who are forced migrants compared with women who are economic migrants. To our knowledge, we have provided the first pooled estimate of perinatal depression and PTSD among women who are forced migrants. Interpreting the prevalence estimate should be observed with caution due to the very wide range found within the included studies. Additionally, 66% of studies were cross-sectional representing low quality evidence. These findings highlight the need for community-based routine perinatal mental health screening for migrant communities, and access to interventions that are culturally sensitive, particularly for forced migrants who might experience a higher burden of disease than economic migrants.
Funding: UK National Institute for Health Research (NIHR); March of Dimes European Preterm Birth Research Centre, Imperial College; Imperial College NIHR Biomedical Research Centre; and Nuffield Department of Population Health, University of Oxford.
The Lancet. Public health · meta-analysis · 63 citationsread the source →
Richards DA, Ekers D, McMillan D, Taylor RS, Byford S, Warren FC, Barrett B, Farrand PA, Gilbody S, Kuyken W, O'Mahen H, Watkins ER, Wright KA, Hollon SD, Reed N, Rhodes S, Fletcher E, Finning K. (2016)MEDLINE-indexed journal, not yet read by usLancet (London, England) · randomised controlled trial Cost and Outcome of Behavioural Activation versus Cognitive Behavioural Therapy for Depression (COBRA): a randomised, controlled, non-inferiority trial.
Background: Depression is a common, debilitating, and costly disorder. Many patients request psychological therapy, but the best-evidenced therapy-cognitive behavioural therapy (CBT)-is complex and costly. A simpler therapy-behavioural activation (BA)-might be as effective and cheaper than is CBT. We aimed to establish the clinical efficacy and cost-effectiveness of BA compared with CBT for adults with depression.
Methods: In this randomised, controlled, non-inferiority trial, we recruited adults aged 18 years or older meeting Diagnostic and Statistical Manual of Mental Disorders IV criteria for major depressive disorder from primary care and psychological therapy services in Devon, Durham, and Leeds (UK). We excluded people who were receiving psychological therapy, were alcohol or drug dependent, were acutely suicidal or had attempted suicide in the previous 2 months, or were cognitively impaired, or who had bipolar disorder or psychosis or psychotic symptoms. We randomly assigned participants (1:1) remotely using computer-generated allocation (minimisation used; stratified by depression severity [Patient Health Questionnaire 9 (PHQ-9) score of <19 vs ≥19], antidepressant use, and recruitment site) to BA from junior mental health workers or CBT from psychological therapists. Randomisation done at the Peninsula Clinical Trials Unit was concealed from investigators. Treatment was given open label, but outcome assessors were masked. The primary outcome was depression symptoms according to the PHQ-9 at 12 months. We analysed all those who were randomly allocated and had complete data (modified intention to treat [mITT]) and also all those who were randomly allocated, had complete data, and received at least eight treatment sessions (per protocol [PP]). We analysed safety in the mITT population. The non-inferiority margin was 1·9 PHQ-9 points. This trial is registered with the ISCRTN registry, number ISRCTN27473954.
Findings: Between Sept 26, 2012, and April 3, 2014, we randomly allocated 221 (50%) participants to BA and 219 (50%) to CBT. 175 (79%) participants were assessable for the primary outcome in the mITT population in the BA group compared with 189 (86%) in the CBT group, whereas 135 (61%) were assessable in the PP population in the BA group compared with 151 (69%) in the CBT group. BA was non-inferior to CBT (mITT: CBT 8·4 PHQ-9 points [SD 7·5], BA 8·4 PHQ-9 points [7·0], mean difference 0·1 PHQ-9 points [95% CI -1·3 to 1·5], p=0·89; PP: CBT 7·9 PHQ-9 points [7·3]; BA 7·8 [6·5], mean difference 0·0 PHQ-9 points [-1·5 to 1·6], p=0·99). Two (1%) non-trial-related deaths (one [1%] multidrug toxicity in the BA group and one [1%] cancer in the CBT group) and 15 depression-related, but not treatment-related, serious adverse events (three in the BA group and 12 in the CBT group) occurred in three [2%] participants in the BA group (two [1%] patients who overdosed and one [1%] who self-harmed) and eight (4%) participants in the CBT group (seven [4%] who overdosed and one [1%] who self-harmed).
Interpretation: We found that BA, a simpler psychological treatment than CBT, can be delivered by junior mental health workers with less intensive and costly training, with no lesser effect than CBT. Effective psychological therapy for depression can be delivered without the need for costly and highly trained professionals.
Funding: National Institute for Health Research.
Lancet (London, England) · randomised controlled trial · 354 citationsread the source →
Linzer M, Poplau S, Grossman E, Varkey A, Yale S, Williams E, Hicks L, Brown RL, Wallock J, Kohnhorst D, Barbouche M. (2015)MEDLINE-indexed journal, not yet read by usJournal of general internal medicine · randomised controlled trial A Cluster Randomized Trial of Interventions to Improve Work Conditions and Clinician Burnout in Primary Care: Results from the Healthy Work Place (HWP) Study.
Background: Work conditions in primary care are associated with physician burnout and lower quality of care.
Objective: We aimed to assess if improvements in work conditions improve clinician stress and burnout.
Subjects: Primary care clinicians at 34 clinics in the upper Midwest and New York City participated in the study.
Study design: This was a cluster randomized controlled trial.
Measures: Work conditions, such as time pressure, workplace chaos, and work control, as well as clinician outcomes, were measured at baseline and at 12-18 months. A brief worklife and work conditions summary measure was provided to staff and clinicians at intervention sites.
Interventions: Diverse interventions were grouped into three categories: 1) improved communication; 2) changes in workflow, and 3) targeted quality improvement (QI) projects.
Analysis: Multilevel regressions assessed impact of worklife data and interventions on clinician outcomes. A multilevel analysis then looked at clinicians whose outcome scores improved and determined types of interventions associated with improvement.
Results: Of 166 clinicians, 135 (81.3%) completed the study. While there was no group treatment effect of baseline data on clinician outcomes, more intervention clinicians showed improvements in burnout (21.8% vs 7.1% less burned out, p = 0.01) and satisfaction (23.1% vs 10.0% more satisfied, p = 0.04). Burnout was more likely to improve with workflow interventions [Odds Ratio (OR) of improvement in burnout 5.9, p = 0.02], and with targeted QI projects than in controls (OR 4.8, p = 0.02). Interventions in communication or workflow led to greater improvements in clinician satisfaction (OR 3.1, p = 0.04), and showed a trend toward greater improvement in intention to leave (OR 4.2, p = 0.06).
Limitations: We used heterogeneous intervention types, and were uncertain how well interventions were instituted.
Conclusions: Organizations may be able to improve burnout, dissatisfaction and retention by addressing communication and workflow, and initiating QI projects targeting clinician concerns.
Journal of general internal medicine · randomised controlled trial · 247 citationsread the source →
Kluger BM, Miyasaki J, Katz M, Galifianakis N, Hall K, Pantilat S, Khan R, Friedman C, Cernik W, Goto Y, Long J, Fairclough D, Sillau S, Kutner JS. (2020)MEDLINE-indexed journal, not yet read by usJAMA neurology · randomised controlled trial Comparison of Integrated Outpatient Palliative Care With Standard Care in Patients With Parkinson Disease and Related Disorders: A Randomized Clinical Trial.
Importance: Parkinson disease and related disorders (PDRD) have consequences for quality of life (QoL) and are the 14th leading cause of death in the United States. Despite growing interest in palliative care (PC) for persons with PDRD, few studies are available supporting its effectiveness.
Objective: To determine if outpatient PC is associated with improvements in patient-centered outcomes compared with standard care among patients with PDRD and their caregivers.
Design, setting, and participants: This randomized clinical trial enrolled participants at 3 academic tertiary care centers between November 1, 2015, and September 30, 2017, and followed them up for 1 year. A total of 584 persons with PDRD were referred to the study. Of those, 351 persons were excluded by phone and 23 were excluded during in-person screenings. Patients were eligible to participate if they had PDRD and moderate to high PC needs. Patients were excluded if they had urgent PC needs, another diagnosis meriting PC, were already receiving PC, or were unable or unwilling to follow the study protocol. Enrolled participants were assigned to receive standard care plus outpatient integrated PC or standard care alone. Data were analyzed between November 1, 2018, and December 9, 2019.
Interventions: Outpatient integrated PC administered by a neurologist, social worker, chaplain, and nurse using PC checklists, with guidance and selective involvement from a palliative medicine specialist. Standard care was provided by a neurologist and a primary care practitioner.
Main outcomes and measures: The primary outcomes were the differences in patient quality of life (QoL; measured by the Quality of Life in Alzheimer Disease scale) and caregiver burden (measured by the Zarit Burden Interview) between the PC intervention and standard care groups at 6 months.
Results: A total of 210 patients with PDRD (135 men [64.3%]; mean [SD] age, 70.1 [8.2] years) and 175 caregivers (128 women [73.1%]; mean [SD] age, 66.1 [11.1] years) were enrolled in the study; 193 participants (91.9%) were white and non-Hispanic. Compared with participants receiving standard care alone at 6 months, participants receiving the PC intervention had better QoL (mean [SD], 0.66 [5.5] improvement vs 0.84 [4.2] worsening; treatment effect estimate, 1.87; 95% CI, 0.47-3.27; P = .009). No significant difference was observed in caregiver burden (mean [SD], 2.3 [5.0] improvement vs 1.2 [5.6] improvement in the standard care group; treatment effect estimate, -1.62; 95% CI, -3.32 to 0.09; P = .06). Other significant differences favoring the PC intervention included nonmotor symptom burden, motor symptom severity, completion of advance directives, caregiver anxiety, and caregiver burden at 12 months. No outcomes favored standard care alone. Secondary analyses suggested that benefits were greater for persons with higher PC needs.
Conclusions and relevance: Outpatient PC is associated with benefits among patients with PDRD compared with standard care alone. This study supports efforts to integrate PC into PDRD care. The lack of diversity and implementation of PC at experienced centers suggests a need for implementation research in other populations and care settings.
Trial registration: ClinicalTrials.gov Identifier: NCT02533921.
JAMA neurology · randomised controlled trial · 136 citationsread the source →
Ader F, Bouscambert-Duchamp M, Hites M, Peiffer-Smadja N, Poissy J, Belhadi D, Diallo A, Lê MP, Peytavin G, Staub T, Greil R, Guedj J, Paiva JA, Costagliola D, Yazdanpanah Y, Burdet C, Mentré F, DisCoVeRy Study Group. (2022)MEDLINE-indexed journal, not yet read by usThe Lancet. Infectious diseases · randomised controlled trial Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial.
Background: The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support.
Methods: DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir-ritonavir, lopinavir-ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948.
Findings: Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77-1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome).
Interpretation: No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support.
Funding: European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation.
Translation: For the French translation of the abstract see Supplementary Materials section.
The Lancet. Infectious diseases · randomised controlled trial · 264 citationsread the source →
Results of a multicenter randomized controlled trial of the clinical effectiveness of schema therapy for personality disorders.
Objective: The authors compared the effectiveness of 50 sessions of schema therapy with clarification-oriented psychotherapy and with treatment as usual among patients with cluster C, paranoid, histrionic, or narcissistic personality disorder.
Method: A multicenter randomized controlled trial, with a single-blind parallel design, was conducted between 2006 and 2011 in 12 Dutch mental health institutes. A total of 323 patients with personality disorders were randomly assigned (schema therapy, N=147; treatment as usual, N=135; clarification-oriented psychotherapy, N=41). There were two cohorts of schema therapy therapists, with the first trained primarily with lectures and the second primarily with exercises. The primary outcome was recovery from personality disorder 3 years after treatment started (assessed by blinded interviewers). Secondary outcomes were dropout rates and measures of personality disorder traits, depressive and anxiety disorders, general psychological complaints, general and social functioning, self-ideal discrepancy, and quality of life.
Results: A significantly greater proportion of patients recovered in schema therapy compared with treatment as usual and clarification-oriented psychotherapy. Second-cohort schema therapists had better results than first-cohort therapists. Clarification-oriented psychotherapy and treatment as usual did not differ. Findings did not vary with specific personality disorder diagnosis. Dropout was lower in the schema therapy and clarification-oriented psychotherapy conditions. All treatments showed improvements on secondary outcomes. Schema therapy patients had less depressive disorder and higher general and social functioning at follow-up. While interview-based measures demonstrated significant differences between treatments, differences were not found with self-report measures.
Conclusions: Schema therapy was superior to treatment as usual on recovery, other interview-based outcomes, and dropout. Exercise-based schema therapy training was superior to lecture-based training.
The American journal of psychiatry · randomised controlled trial · 189 citationsread the source →
Effectiveness of internet-based cognitive behavioural treatment for adolescents with chronic fatigue syndrome (FITNET): a randomised controlled trial.
Background: Chronic fatigue syndrome is characterised by persistent fatigue and severe disability. Cognitive behavioural therapy seems to be a promising treatment, but its availability is restricted. We developed Fatigue In Teenagers on the interNET (FITNET), the first dedicated internet-based therapeutic program for adolescents with this disorder, and compared its effectiveness with that of usual care.
Methods: Adolescents aged 12-18 years with chronic fatigue syndrome were assigned to FITNET or usual care in a 1:1 ratio at one tertiary treatment centre in the Netherlands by use of a computer-generated blocked randomisation allocation schedule. The study was open label. Primary outcomes were school attendance, fatigue severity, and physical functioning, and were assessed at 6 months with computerised questionnaires. Analysis was by intention to treat. Thereafter, all patients were offered FITNET if needed. This trial is registered, number ISRCTN59878666.
Findings: 68 of 135 adolescents were assigned to FITNET and 67 to usual care, and 67 and 64, respectively, were analysed. FITNET was significantly more effective than was usual care for all dichotomised primary outcomes at 6 months-full school attendance (50 [75%] vs 10 [16%], relative risk 4·8, 95% CI 2·7-8·9; p<0·0001), absence of severe fatigue (57 [85%] vs 17 [27%], 3·2, 2·1-4·9; p<0·0001), and normal physical functioning (52 [78%] vs 13 [20%], 3·8, 2·3-6·3; p<0·0001). No serious adverse events were reported.
Interpretation: FITNET offers a readily accessible and highly effective treatment for adolescents with chronic fatigue syndrome. The results of this study justify implementation on a broader scale.
Funding: Netherlands Organisation for Health Research and Development.
Lancet (London, England) · randomised controlled trial · 140 citationsread the source →
Community based physiotherapeutic exercise in COPD self-management: a randomised controlled trial.
Little is known about effects of community-based physiotherapeutic exercise programmes incorporated in COPD self-management programmes. In a randomised trial, the effect of such a programme (COPE-active) on exercise capacity and various secondary outcomes including daily activity as a marker of behaviour change was evaluated. All patients attended four 2-h self-management sessions. In addition the intervention group participated in the COPE-active programme offered by physiotherapists of private practices, consisting of a 6-month "compulsory" period (3 sessions/week) and subsequently a 5-month "optional" period (2 sessions/week). Because COPE-active was intended to change behaviour with regard to exercise, one session/week in both periods consisted of unsupervised home-based exercise training. Of 153 patients, 74 intervention and 68 control patients completed the one-year follow-up. Statistically significant between-group differences in incremental shuttle walk test-distance (35.1 m; 95% CI (8.4; 61.8)) and daily activity (1190 steps/day; 95% CI (256; 2125)) were found in favour of the intervention group. Over the 12-month period a significant difference of the chronic respiratory questionnaire (CRQ) dyspnoea-score (0.33 points; 95% CI (0.01; 0.64)) and a non-significant difference of the endurance shuttle walk test (135 m (95% CI (-29; 298)) was found. No differences were found in the other CRQ-components, anxiety and depression scores and percentage of fat free mass. This study demonstrates that a community-based reactivation programme improves exercise capacity in patients with moderately to severe COPD. Even more important, the programme improves actual daily activity after one-year which indicates behaviour change with regard to daily exercise. Registered trail number: ISRCTN81447311.
Respiratory medicine · randomised controlled trial · 83 citationsread the source →
Long-term effects of the family bereavement program on multiple indicators of grief in parentally bereaved children and adolescents.
Objectives: This article reports on results from a randomized experimental trial of the effects of the Family Bereavement Program (FBP) on multiple measures of grief experienced by parentally bereaved children and adolescents over a 6-year period.
Method: Participants were 244 youths (ages 8-16, mean age = 11.4 years) from 156 families that had experienced the death of a parent. The sample consisted of 53% boys and 47% girls; ethnicity was 67% non-Hispanic White and 33% ethnic minority. Families were randomly assigned to the FBP (N = 135) or a literature control condition (N = 109). Two grief measures, the Texas Revised Inventory of Grief and the Intrusive Grief Thoughts Scale (IGTS) were administered at 4 times over 6 years: pretest, posttest, and 11-month and 6-year follow-ups. A 3rd measure, an adaptation of the Inventory of Traumatic Grief (ITG) was administered only at the 6-year follow-up.
Results: Compared with the control group, the FBP group showed a greater reduction in their level of problematic grief (IGTS) at posttest and 6-year follow-up and in the percentage at clinical levels of problematic grief at the posttest. The FBP also reduced scores on a dimension of the ITG, Social Detachment/Insecurity, at 6-year follow-up for 3 subgroups: those who experienced lower levels of grief at program entry, older youths, and boys.
Conclusion: These are the first findings from a randomized trial with long-term follow-up of the effects of a program to reduce problematic levels of grief of parentally bereaved youths.
Journal of consulting and clinical psychology · randomised controlled trial · 67 citationsread the source →
Coparenting relationship trajectories: Marital violence linked to change and variability after separation.
Associations between marital intimate partner violence (IPV) and postseparation coparenting relationship trajectories were examined among 135 mothers who participated in 5 interviews at 3-month intervals in the year following their divorce filing. Growth curve analysis was conducted to assess change and variability in coparenting dimensions (i.e., conflict, support, communication about child rearing, and harassment) in the overall sample and by type of IPV. In the overall sample, coparenting conflict, communication about child rearing, and harassment decreased across the year following separation. However, coparenting relationships differed considerably based on marital IPV experiences. At Time 1, mothers in relationships with coercive controlling violence (CCV) reported higher levels of harassment and conflict, and lower levels of support and communication about coparenting, than mothers with situational couple violence (SCV) or no violence (NV). Furthermore, coparenting relationship trajectories differed significantly by IPV group, with mothers who experienced CCV showing more variability in conflict and harassment, and more marked changes in conflict, support, and harassment. Despite many similarities, mothers with SCV showed higher initial levels of harassment compared to mothers with NV. Findings can support family court and social service professionals' efforts to individualize interventions with divorcing parents based on IPV experiences. In cases of CCV, for example, attention to heightened control dynamics in the immediate separation period remain critical but the persistent volatility across the first year suggests the potential for chronic stress. With SCV, practitioners may be able to capitalize on parents' reasonable levels of communication and steady coparenting support. (PsycINFO Database Record
Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) · 10 citationsread the source →
Essential Hypertension
HomeCirculationVol. 101, No. 3Essential Hypertension Free AccessOtherPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessOtherPDF/EPUBEssential Hypertension Part I: Definition and Etiology Oscar A. Carretero and Suzanne Oparil Oscar A. CarreteroOscar A. Carretero From the Hypertension and Vascular Research Division, Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich (O.A.C.), and the Division of Cardiovascular Disease, Vascular Biology and Hypertension Program, University of Alabama School of Medicine, Birmingham (S.O.). and Suzanne OparilSuzanne Oparil From the Hypertension and Vascular Research Division, Heart and Vascular Institute, Henry Ford Hospital, Detroit, Mich (O.A.C.), and the Division of Cardiovascular Disease, Vascular Biology and Hypertension Program, University of Alabama School of Medicine, Birmingham (S.O.). Originally published25 Jan 2000https://doi.org/10.1161/01.CIR.101.3.329Circulation. 2000;101:329–335Essential hypertension remains a major modifiable risk factor for cardiovascular disease (CVD) despite important advances in our understanding of its pathophysiology and the availability of effective treatment strategies. High blood pressure (BP) increases the risk of CVD for millions of people worldwide, and there is evidence that the problem is only getting worse. In the past decade, age-adjusted rates of stroke incidence have risen, and the slope of the age-adjusted rate of decline in coronary disease has leveled off. The incidence of end-stage renal disease and the prevalence of heart failure have also increased. A major contributor to these trends is inadequate control of BP in the hypertensive population. This review of current concepts regarding the definition, etiology, and treatment of essential hypertension is intended to aid the clinician in identifying those individuals at high risk who need to undergo evaluation and treatment, as well as in selecting optimal treatment strategies for hypertensive patients with comorbid conditions and/or target organ damage. The part of the review that deals with the genetic basis of hypertension and the gene/environment interaction that may lead to elevated BP is still a work in progress. Information gained from the Human Genome Project and from ongoing studies of the genetic basis of hypertension both in animal models and human populations may revolutionize the treatment of hypertension by replacing current empirical therapy with more effective, targeted treatments based on the genotype of the patient. Concepts introduced in this review form the basis for such "pharmacogenomic" approaches to antihypertensive therapy. Definition of Essential or Primary HypertensionBP is a quantitative trait that is highly variable1 ; in population studies, BP has a normal distribution that is slightly skewed to the right. There is a strong positive and continuous correlation between BP and the risk of CVD (stroke, myocardial infarction, heart failure), renal disease, and mortality, even in the normotensive range. This correlation is more robust with systolic than with diastolic BP.2 There is no specific level of BP where cardiovascular and renal complications start to occur; thus the definition of hypertension is arbitrary but needed for practical reasons in patient assessment and treatment. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) defined and classified hypertension in adults, as shown in Table 1.3 The diagnosis of hypertension is made when the average of 2 or more diastolic BP measurements on at least 2 subsequent visits is ≥90 mm Hg or when the average of multiple systolic BP readings on 2 or more subsequent visits is consistently ≥140 mm Hg. Isolated systolic hypertension is defined as systolic BP ≥140 mm Hg and diastolic BP <90 mm Hg. Individuals with high normal BP tend to maintain pressures that are above average for the general population and are at greater risk for development of definite hypertension and cardiovascular events than the general population. With the use of these definitions, it is estimated that 43 million people in the United States have hypertension or are taking antihypertensive medication, which is ≈24% of the adult population. This proportion changes with (1) race, being higher in blacks (32.4%) and lower in whites (23.3%) and Mexican Americans (22.6%); (2) age, because in industrialized countries systolic BP rises throughout life, whereas diastolic BP rises until age 55 to 60 years and thus the greater increase in prevalence of hypertension among the elderly is mainly due to systolic hypertension; (3) geographic patterns, because hypertension is more prevalent in the southeastern United States; (4) gender, because hypertension is more prevalent in men (though menopause tends to abolish this difference); and (5) socioeconomic status, which is an indicator of lifestyle attributes and is inversely related to the prevalence, morbidity, and mortality rates of hypertension. Essential, primary, or idiopathic hypertension is defined as high BP in which secondary causes such as renovascular disease, renal failure, pheochromocytoma, aldosteronism, or other causes of secondary hypertension or mendelian forms (monogenic) are not present. Essential hypertension accounts for 95% of all cases of hypertension. Essential hypertension is a heterogeneous disorder, with different patients having different causal factors that lead to high BP. Essential hypertension needs to be separated into various syndromes because the causes of high BP in most patients presently classified as having essential hypertension can be recognized. Known Etiological Factors in Essential HypertensionAlthough it has frequently been indicated that the causes of essential hypertension are not known, this is only partially true because we have little information on genetic variations or genes that are overexpressed or underexpressed as well as the intermediary phenotypes that they regulate to cause high BP.4 A number of factors increase BP, including (1) obesity, (2) insulin resistance, (3) high alcohol intake, (4) high salt intake (in salt-sensitive patients), (5) aging and perhaps (6) sedentary lifestyle, (7) stress, (8) low potassium intake, and (9) low calcium intake.56 Furthermore, many of these factors are additive, such as obesity and alcohol intake. In this review, variations in BP that are genetically determined will be called "inherited BP," although we do not know which genes cause BP to vary; we know from family studies that inherited BP can range from low normal BP to severe hypertension. Factors that increase BP, such as obesity and high alcohol and salt intake, will be called "hyperten-sinogenic factors." Some of these factors have inherited, behavioral, and environmental components. Inherited BP could be considered core BP, whereas hypertensinogenic factors cause BP to increase above the range of inherited BPs, thus creating 4 main possibilities: (1) patients who have inherited BP in the optimal category (<120/<80 mm Hg); if 1 or more hypertensinogenic factors are added, BP would probably increase but remain in the normal range (<135/<85 mm Hg) (Figure 1, first 2 columns); (2) patients who have inherited BP in the normal category (≤130/≤85 mm Hg); if 1 or more hypertensinogenic factors are added, BP will probably increase to the high normal range (130 to 139/85 to 89 mm Hg) or to stage 1 of the hypertensive category (140 to 159/90 to 99 mm Hg) (Figure 1, second 2 columns); (3) patients who have inherited BP in the high normal category (130 to 139/85 to 89 mm Hg); if 1 or more hypertensinogenic factors are added, BP will increase to the hypertensive range (≥140/≥90 mm Hg) (Figure 1, third 2 columns); and (4) patients who have inherited BP in the hypertensive range; addition of 1 or more hypertensinogenic factors will make hypertension more severe, changing it from stage 1 to stage 2 or 3 (Figure 1, fourth to sixth 2 columns).Theoretically, in a population unaffected by hypertensinogenic factors, BP will have a normal distribution; it will be skewed to the right and will have a narrow base or less variance (Figure 2, continuous line). When 1 hypertensinogenic factor is added to this population, such as increased body mass, one would expect the normal distribution curve to be further skewed to the right; consequently the base will be wider (more variance) and the curve will be flatter (Figure 2, broken line). If a second hypertensinogenic factor such as alcohol intake is added to increased body mass, the curve will be skewed more to the right and the variance will increase further, with more subjects classified as hypertensive (Figure 2, dotted line).Discovering which genetic variations place BP on the left or right side of the distribution curve is of both theoretical and practical importance because it could help the physician to better treat or cure hypertension.7 Recognition of the hypertensinogenic factors may allow nonpharmacological prevention, treatment, or cure of hypertension. Hypertensinogenic factors such as obesity, insulin resistance, or high alcohol intake also have an important genetic component. Furthermore, there are interactions between genetic and environmental factors (Figure 2) that influence intermediary phenotypes such as sympathetic nerve activity, the renin-angiotensin-aldosterone and renal kallikrein-kinin systems, and endothelial factors, which in turn influence other intermediary phenotypes such as sodium excretion, vascular reactivity, and cardiac contractility. These and many other intermediary phenotypes determine total vascular resistance and cardiac output and, consequently, BP. Recognition of the hypertensinogenic factor(s) and establishing that the patient's hypertension is the result of obesity (either alone or combined with other factors such as insulin resistance or high alcohol intake) or old age instead of essential hypertension may help the physician as well as the patient and his or her family to modify or eliminate these hypertensinogenic and CVD risk factors when possible, which may cure the hypertension or at least facilitate control of BP. When the hypertensinogenic factor cannot be reduced or eliminated, as with systolic hypertension induced by aging (arteriosclerosis), recognition of the underlying cause of high BP will emphasize the need for (1) further studies to determine whether the patient has arteriosclerosis and/or atherosclerosis, the magnitude of the disease, and whether there are occlusive lesions; (2) treatment of the atherosclerosis with lifestyle and dietary changes and lipid-lowering agents if necessary; and (3) pharmacological treatment of systolic hypertension to decrease passive stiffness (arteriosclerosis) of the major central elastic arteries and decrease morbidity and mortality rates. Thus recognition of factors that induce hypertension is not only of theoretical but also of practical importance. In conclusion, as stated by Beilin,8 "it is no longer appropriate to define essential hypertension as a rise in blood pressure without cause," since a number of causes can be clearly identified in most cases of so-called "essential hypertension." As discussed later in more detail, there is clear evidence that changes in lifestyle, including dietary changes that reduce body weight, fat, and alcohol intake and increase potassium and calcium intake,9 as well as exercise,1011 reduce or normalize BP in many patients. Inherited BPThe identification of variant (allelic) genes that contribute to the development of hypertension is complicated by the fact that the 2 phenotypes that determine BP, cardiac output and total peripheral resistance, are controlled by intermediary phenotypes, including the autonomic nervous system, vasopressor/vasodepressor hormones, the structure of the cardiovascular system, body fluid volume and renal function, and many others. Furthermore, these intermediary phenotypes are also controlled by complex mechanisms including BP itself.12 Thus there are many genes that could participate in the development of hypertension. The influence of genes on BP has been suggested by family studies demonstrating associations of BP among siblings and between parents and children. There is a better association among BP values in biological children than in adopted children and in identical as opposed to nonidentical twins. BP variability attributed to all genetic factors varies from 25% in pedigree studies to 65% in twin studies. Furthermore, genetic factors also influence behavioral patterns, which might lead to BP elevation. For example, a tendency toward obesity or alcoholism will be influenced by both genetic and environmental factors; thus the proportion of BP variability caused by inheritance is difficult to determine and may vary in different populations. Mutations in at least 10 genes have been shown to raise or lower BP through a common pathway by increasing or decreasing salt and water reabsorption by the nephron.1314 The genetic mutations responsible for 3 rare forms of mendelian (monogenic) hypertensive syndromes−glucocorticoid-remediable aldosteronism (GRA), Liddle's syndrome, and apparent mineralocorticoid excess−have been identified, whereas in a fourth, autosomal dominant hypertension with brachydactyly, the gene is not yet identified but has been mapped to chromosome 12 (12p). Subtle variations in one of these genes may also cause some forms of "essential" hypertension. For a review of the mutations that cause a decrease in BP, see Lifton.13Glucocorticoid-Remediable AldosteronismThis is an autosomal dominant form of monogenic hypertension in which aldosterone secretion is regulated by adrenocorticotropic hormone. Glucocorticoid treatment causes BP to decrease and gives the syndrome its name. The genetic mutation that causes GRA has been identified by Lifton14 as a chimeric gene fusing nucleotide sequences of the promoter-regulatory region of 11β-hydroxylase (controlled by adrenocorticotropic hormone) and the structural portion of the aldosterone synthase gene. The chimeric gene results from a meiotic mismatch and unequal crossing over. The patients are usually thought to have primary aldosteronism because they exhibit volume expansion, metabolic alkalosis with hypokalemia, low plasma renin, and high aldosterone. Most of the patients first described as having GRA showed severe hypertension and died prematurely from stroke. However, with the development of direct genetic testing, the BP of patients with this syndrome was found to cover a wide range, including normotensive levels.1516 In patients with GRA and normal BP, expression of the chimeric gene may be variable, but because steroid levels are similar in patients with severe and mild hypertension, this seems unlikely. It is also possible that the genetic background of the trait (other than the chimeric mutation), such as high renal kallikrein, places the inherited BP of these subjects in the low or ideal normal range and the mutation causes BP to increase to high normal or hypertensive stage 1. Thus the final BP would be the combined result of the inherited BP (including the genetic mutation) and the increase in BP caused by hypertensinogenic factors such as salt. Liddle's SyndromeThis is an autosomal dominant form of monogenic hypertension that results from mutations in the amiloride-sensitive epithelial sodium channel, leading to increased channel activity.17 The mutations reported to date result in the elimination of 45 to 75 amino acids from the cytoplasmic carboxyl terminus of β- or γ-subunits of the channel; thus Liddle's syndrome is genetically heterogeneous. It is characterized by the early onset of hypertension with hypokalemia and suppression of both plasma renin activity and aldosterone, the latter differentiating this syndrome from primary aldosteronism. Both the hypertension and the hypokalemia vary in severity, raising the possibility that some patients classified as having salt-sensitive essential hypertension actually have Liddle's syndrome.18 It is also possible that high BP in blacks, who are frequently salt-sensitive, is due to a polymorphism in one of the sodium channel genes or in one of the genes of systems that regulate it, causing its activity to increase. Apparent Mineralocorticoid ExcessThis is an autosomal recessive form of monogenic juvenile hypertension that results from a mutation in the renal-specific isoform 11β-hydroxysteroid dehydrogenase gene.19 Normally this enzyme converts cortisol to the inactive metabolite cortisone. In the distal nephron this is important because cortisol and aldosterone have a similar affinity for the mineralocorticoid receptor. The enzymatic deficiency allows the mineralocorticoid receptors in the nephron to be occupied and activated by cortisol, causing sodium and water retention, volume expansion, low renin, low aldosterone, and more importantly, a salt-sensitive form of hypertension. Thus this gene may be a locus for salt-sensitive essential hypertension. Autosomal Dominant Hypertension With BrachydactylyIn this monogenic syndrome, hypertension and brachydactyly are always inherited together (100% cosegregation).4 Affected persons are shorter than nonaffected relatives. The gene for hypertension has been mapped to the short arm of chromosome 12 (12p) in a large Turkish kindred. Two other families with this syndrome have been reported, 1 in Canada and 1 in the United States. In addition, the study of a Japanese child with hypertension and type E brachydactyly has allowed the area on 12p containing the gene mutation to be pinpointed further, although the gene responsible for this syndrome has not yet been cloned. Unlike the other 3 autosomal forms of hypertension, BP is not affected by volume expansion and the underlying mechanism is not known. Thus identification of the gene responsible may help clarify some of the genetic alterations in essential hypertension. Essential or Primary HypertensionThe genetic alterations responsible for inherited "essential" hypertension remain largely unknown.4 Results from family studies suggest several possible intermediary phenotypes (genetic traits) that may be related to inherited high BP, such as high sodium-lithium countertransport, low urinary kallikrein excretion, high fasting plasma insulin concentrations, high-density LDL subfractions, fat pattern index, and body mass index (BMI).12 Jeunemaitre et al2021 first reported a polymorphism in the angiotensinogen gene linked with essential hypertension in hypertensive siblings from Utah and France. This polymorphism consists of a substitution of thymidine for cytosine in nucleotide 704, which causes substitution of methionine for threonine at position 235 (M235T) and is associated with increased concentrations of plasma angiotensinogen. This variant appears to be in tight linkage disequilibrium with a promoter mutation in which adenine replaces guanine (-6A) upstream from the initiation side of transcription.22 Tests of promoter activity suggest that this nucleotide substitution increases the rate of gene transcription, which may explain the higher angiotensinogen concentration found in subjects with the variant M235T.22 Many studies have been published on various racial groups with regard to the association between allelic variations in angiotensinogen and hypertension.23 However, these variations explain only a small part of the BP variation (≈6%). Furthermore, plasma angiotensinogen concentrations, though higher in patients with the polymorphism, clearly overlap with normotensive patients. Polymorphisms and mutations in other genes such as angiotensin-converting enzyme, β2-adrenergic receptor, α-adducin, angiotensinase C, renin-binding protein, G-protein β3-subunit, atrial natriuretic factor, and the insulin receptor have also been linked to the development of essential hypertension; however, most of them show a weak association if any, and most of these studies need further confirmation. Thus these gene alterations will not be discussed here because they go beyond the scope of this review (see Luft4 ).Hypertensinogenic FactorsThere is evidence that obesity, insulin resistance, high alcohol intake, high salt intake, a sedentary lifestyle, stress, dyslipidemia, and low potassium or calcium intake increase BP in susceptible subjects. Here we will briefly discuss obesity and insulin resistance; other hypertensinogenic factors will be discussed in the section "Lifestyle Modification."Obesity and Insulin ResistanceObesity, and obesity, is the main hypertensinogenic It was estimated in the study that is associated with a mm Hg increase in systolic is also the cause of insulin resistance, left and Thus obesity is an important cardiovascular its incidence and prevalence are in most industrialized and in the United States has The between BP and body fat is not to the but is continuous throughout the range of body A direct association between hypertension and in by the in has been in and population studies from early to old A of is considered normal or whereas a of to with increases the risk of high BP by and the risk of insulin resistance by Thus insulin resistance is in many patients with obesity and hypertension. The mechanism by which obesity BP is not but increased is associated with an increase in plasma volume and cardiac both these alterations and BP can be by in both normotensive and hypertensive even when sodium intake is BP in is and fasting insulin is the of this In these BP by 10 mm Hg changing from 2 on a to a When some of these subjects by BP by 10 mm Hg and salt was no longer present. The that sodium fasting plasma plasma aldosterone, and plasma the that BP is to dietary sodium and that this may be due to the combined of and increased activity of the sympathetic nervous It is not clear whether body fat by is a factor because in for 1 3 BP, and this decrease was mainly in those who high fasting insulin and insulin levels in to In this study was not a factor because the subjects on a and actually gained an average of the which that plasma insulin by a different mechanism than of body These studies can be as that high plasma insulin causes salt and that decreasing insulin resistance by or BP. Furthermore, hypertensive subjects are more to exhibit insulin resistance than normotensive the other insulin by has a In subjects with hypertension there is resistance to the of insulin on However, in addition to this metabolic insulin increases both sympathetic nerve activity and sodium and water retention, and it could be that the hypertension is due to the of resistance to these secondary of factor and a that have also been in the of hypertension. although the mechanisms by which obesity and insulin resistance increase BP remain it is clear that these increases in BP are on the inherited of of the evaluation are to determine the and of target organ and for specific causes of hypertension hypertensinogenic factors and other CVD risk factors; and the patient to facilitate the of therapy and define and of BP by the is the most important part of the evaluation and of the patient and be in a 2) with the use of and A is a or a to an arm Two or 3 measurements be at and at least 2 be allowed between The diastolic is at the level when of BP by patients or family and/or BP the diagnosis and the of hypertension. BP values the are lower and better with target organ than BP measurements by of BP has several including hypertension from hypertension that only in the the to antihypertensive to treatment by the patient a in his or her and by the need for BP or of BP is for many patients with high BP, those who to be to antihypertensive A of or BP measurements is that and BP be and that and in to BP be and be and a in all patients The assessment the described in Table It help to known, causes of high the or of target organ and and other CVD or comorbid conditions that might or Tests and only blood blood fasting total and high-density or and a indicated in patients for the diagnosis of secondary hypertension and/or comorbid conditions urinary protein, of fasting and plasma renin is Part of a Part of this will be published in the 1, of 1. of hypertensinogenic factors such as obesity and alcohol intake on systolic and diastolic BP the stage of inherited BP to without the of the hypertensinogenic with normal or high normal inherited BP hypertensive stage 1 when BP is increased by a hypertensinogenic In patients with inherited hypertension in 1 to hypertension more severe when hypertensinogenic factors are among genetic and environmental factors in the development of hypertension. side of environmental factors and multiple genes responsible for high BP and intermediary The result of these intermediary phenotypes is blood pressure with a normal distribution skewed to the right. the theoretical BP of the population that is not affected by hypertensinogenic factors; area systolic BP in the hypertensive range. and dotted populations in which 1 or 2 hypertensinogenic factors high alcohol intake) have been that in these 2 populations the distribution are to the right and the number of hypertensive individuals is increased when hypertensinogenic factors are Table 1. and of Blood Pressure mm mm 1 2 3 systolic a patient's systolic and
Circulation · review · 1085 citationsread the source →
Frequency of Pornography Use and Sexual Health Outcomes in Sweden: Analysis of a National Probability Survey.
Background: Little is known about pornography use and its relationship with sexual health outcomes in the general population.
Aim: To assess frequency of pornography use and the association of sexual health outcomes with frequent pornography use in Sweden.
Methods: Cross-sectional analysis of 14,135 participants (6,169 men and 7,966 women) aged 16-84 years in a Swedish nationally representative survey from 2017. We used logistic regression to assess the association of sexual health outcomes with use of pornography ≥3 times/wk.
Outcomes: Frequency of pornography use (never; less than once/mo to 3 times/mo; 1-2 times/wk; 3-5 times/wk; and daily or almost daily) and sexual health outcomes (eg, sexual satisfaction and sexual health problems).
Results: In total, 68.7% of men and 27.0% of women used pornography. Among men aged 16-24 years, 17.2% used pornography daily or almost daily, 24.7% used pornography 3-5 d/wk and 23.7% used pornography 1-2 d/wk. Among women aged 16-24 years, the proportions were 1.2% for daily or almost daily, 3.1% for 3-5 times/wk, and 8.6% for 1-2 times/wk. Frequency of pornography use decreased with age among both men and women. While 22.6% of all men and 15.4% of all women reported that their or a sex partner's pornography use predominantly had positive effects on their sex life, 4.7% of men and 4.0% of women reported that the effects were predominantly negative. Variables indicating sexual dissatisfaction and sexual health problems were associated with use of pornography ≥3 times/wk: for example, dissatisfaction with sex life (age-adjusted odds ratio [aOR]: men 2.90 [95% CI 2.40-3.51]; women 1.85 [95% CI 1.09-3.16]), not having sex in the preferred way (aOR: men 2.48 [95% CI 1.92-3.20]; women 3.59 [95% CI 2.00-6.42]) and erection problems (aOR: men 2.18 [95% CI 1.73-2.76]).
Clinical implications: While frequent pornography use is common, potential effects on sexual health outcomes are likely to differ between individuals.
Strength & limitations: We used a large and recent nationally representative survey with detailed information regarding frequency of pornography use. The temporality of associations of sexual health variables with frequency of pornography use could not be assessed.
Conclusion: In this analysis of a nationally representative survey in Sweden, we found that frequent pornography use was common among young men; that reporting predominantly positive effects of pornography use on the sex life was more common than reporting predominantly negative effects; and that sexual dissatisfaction and sexual health problems were associated with using pornography ≥3 times/wk. Malki K, Rahm C, Öberg KG, et al. Frequency of Pornography Use and Sexual Health Outcomes in Sweden: Analysis of a National Probability Survey. J Sex Med 2021;18:1735-1751.
The journal of sexual medicine · 26 citationsread the source →
Higher Grit Scores Are Associated With Earlier Increases in Knee Flexion Following Anterior Cruciate Ligament Reconstruction With Meniscus Repair in Pediatric Patients.
Background: The Grit Scale is used to measure grit, defined by Duckworth and colleagues as the disposition to show perseverance and passion for long-term goals. It has been shown that psychological factors like motivation, coachability, and coping with adversity are correlated with faster readiness for return to sport (RTS) in patients undergoing anterior cruciate ligament reconstruction (ACLR). This study investigates the association between pediatric patients' baseline grit scores and; preoperative Patient-reported Outcomes Measurement Information System (PROMIS) Pain scores and the recovery of range of motion (ROM) after ACLR. The investigators hypothesized that higher preoperative grit scores would predict lower preoperative pain scores and earlier return of knee ROM in patients undergoing ACLR.
Methods: This is a retrospective cohort study. Pediatric patients who underwent primary ACLR were assigned the pediatric Grit Scale. Patients were subdivided by meniscal procedures due to differences in postoperative protocols. ACLR alone or with meniscectomy (ACLR ± meniscectomy) were grouped together and ACLR with meniscal repair (ACLR + meniscus repair) represented the other cohort. Patients above the 50th grit percentile were considered "high grit". Patients below the 50th percentile were considered "low grit". Baseline PROMIS pain intensity and interference were collected. ROM was compared by grit cohort using the Mann-Whitney U test with a significance threshold of P ≤ 0.05.
Results: A total of 58 patients undergoing ACLR were analyzed: 20 ACLR ± meniscectomy and 38 ACLR + meniscus repair. The mean age was 15.0 ± 2.1 years with 41.4% of participants identifying as females. No significant difference was noted between baseline PROMIS pain intensity and interference and grit score ( P = 0.82, P = 0.91, respectively). Three months postoperatively, for those in the ACLR + meniscus repair cohort, low grit ROM was 130 degrees (interquartile range = 10 degrees), whereas high grit ROM was 135 degrees (interquartile range = 8 degrees) ( P = 0.006).
Conclusions: This study found no differences in pain scores at presentation between grit cohorts but found that patients with grit scores below the 50th percentile undergoing ACLR + meniscus repair have 5 degrees less total ROM at 3 months compared with those with high grit scores. Quicker ROM recovery in patients with high grit may be a leading indicator of these patients' likelihood to achieve other postoperative milestones and meet criteria for RTS more quickly; the relationship between grit and readiness for RTS should be further investigated.
Level of evidence: Level IV; retrospective cohort study.
Journal of pediatric orthopedics · 3 citationsread the source →
Zhang F, Liu W, Yang H, Sun Y, Lei X, Ding Y, Zhang X, Hu Z, Hu S, Wang Z, Cheng W. (2025)MEDLINE-indexed journal, not yet read by usChild and adolescent psychiatry and mental health Reducing anxiety and depression in Chinese adolescents through group behavioral activation: a pilot study with school-based implementation.
Background: Anxiety and depression are increasingly prevalent public health concerns among adolescents. Group Behavioral Activation Therapy (GBAT), a structured school-based intervention, has shown promise as a potential approach for alleviating these conditions.
Methods: This quasi-experimental trial evaluated the efficacy of school-implemented GBAT in reducing anxiety and depressive symptoms among Chinese adolescents. Participants (N = 139; aged 12-17 years; 44.6% male) were assigned to either a GBAT group (n = 72) or a waitlist control group (n = 67). The GBAT protocol consisted of eight weekly 90-minute sessions. Outcomes were assessed at baseline, post-intervention, and 3-month follow-up using the Screen for Child Anxiety Related Emotional Disorders (SCARED) and the Depression Self-Rating Scale for Children (DSRSC).
Results: A total of 93.06% of students completed all eight GBAT sessions. Post-intervention SCARED scores decreased significantly, t (135) = 2.44, MD = 4.20, 95% CI [0.79, 7.60], p = 0.016, Cohen's d = 0.42. Linear mixed-model analysis revealed a significant group effect (F (1,397) = 10.60, p = 0.001), indicating lower anxiety scores in the GBAT group compared with the waitlist control. A significant time effect was also observed, F (1,397) = 7.64, p < 0.001. At 3-month follow-up, GBAT maintained significant improvement in anxiety (SCARED: MD = 8.69, 95% CI [3.58, 13.80], p < 0.001 Cohen's d = 0.82) and depressive symptoms (DSRSC: MD = 2.28, 95% CI [0.10, 4.46], p = 0.037, Cohen's d = 0.43), indicating moderate to large effect sizes.
Conclusions: These preliminary findings suggest that GBAT may be a promising primary prevention strategy for adolescent mental health. This study provides a foundation for future research exploring its potential integration into school-based mental health frameworks.
Child and adolescent psychiatry and mental healthread the source →
Implementation of a psychosocial support package for people receiving treatment for multidrug-resistant tuberculosis in Nepal: A feasibility and acceptability study.
Background and objectives: People receiving treatment for multidrug-resistant tuberculosis (MDR-TB) have high rates of depression. Psychosocial support in general, and treatments for depression in particular, form an important but neglected area of patient-centred care, and a key pillar in the global End TB strategy. We assessed the feasibility and acceptability of a psychosocial support package for people receiving treatment for MDR-TB in Nepal.
Methods: This feasibility study used a mixed quantitative and qualitative approach. We implemented the intervention package in two National Tuberculosis Programme (NTP) MDR-TB treatment centres and 8 sub-centres. We screened patients monthly for depression and anxiety (cut-off ≥24 and ≥17 respectively on the Hopkins Symptom Checklist) and also for low social support (cut-off ≤3 on the Multidimensional Scale of Perceived Social Support). Those who screened positive on either screening tool received the Healthy Activity Program (HAP), which uses brief counselling based on behavioural activation theory. Other aspects of the psychosocial package were information/education materials and group interactions with other patients.
Results: We screened 135 patients, of whom 12 (9%) received HAP counselling, 115 (85%) received information materials, 80 (59%) received an education session and 49 (36%) received at least one group session. Eight group sessions were conducted in total. All aspects of the intervention package were acceptable to patients, including the screening, information, group work and counselling. Patients particularly valued having someone to talk to about their concerns and worries. We were able to successfully train individuals with no experience of psychological counselling to deliver HAP.
Conclusion: This psychosocial support package is acceptable to patients. The information materials we developed are feasible to deliver in the current NTP. However, the structured psychological counselling (HAP), is not feasible in the current NTP due to time constraints. This requires additional investment of counsellors in TB clinics.
PloS one · 25 citationsread the source →
Social connection and mortality in UK Biobank: a prospective cohort analysis.
Background: Components of social connection are associated with mortality, but research examining their independent and combined effects in the same dataset is lacking. This study aimed to examine the independent and combined associations between functional and structural components of social connection and mortality.
Methods: Analysis of 458,146 participants with full data from the UK Biobank cohort linked to mortality registers. Social connection was assessed using two functional (frequency of ability to confide in someone close and often feeling lonely) and three structural (frequency of friends/family visits, weekly group activities, and living alone) component measures. Cox proportional hazard models were used to examine the associations with all-cause and cardiovascular disease (CVD) mortality.
Results: Over a median of 12.6 years (IQR 11.9-13.3) follow-up, 33,135 (7.2%) participants died, including 5112 (1.1%) CVD deaths. All social connection measures were independently associated with both outcomes. Friends/family visit frequencies < monthly were associated with a higher risk of mortality indicating a threshold effect. There were interactions between living alone and friends/family visits and between living alone and weekly group activity. For example, compared with daily friends/family visits-not living alone, there was higher all-cause mortality for daily visits-living alone (HR 1.19 [95% CI 1.12-1.26]), for never having visits-not living alone (1.33 [1.22-1.46]), and for never having visits-living alone (1.77 [1.61-1.95]). Never having friends/family visits whilst living alone potentially counteracted benefits from other components as mortality risks were highest for those reporting both never having visits and living alone regardless of weekly group activity or functional components. When all measures were combined into overall functional and structural components, there was an interaction between components: compared with participants defined as not isolated by both components, those considered isolated by both components had higher CVD mortality (HR 1.63 [1.51-1.76]) than each component alone (functional isolation 1.17 [1.06-1.29]; structural isolation 1.27 [1.18-1.36]).
Conclusions: This work suggests (1) a potential threshold effect for friends/family visits, (2) that those who live alone with additional concurrent markers of structural isolation may represent a high-risk population, (3) that beneficial associations for some types of social connection might not be felt when other types of social connection are absent, and (4) considering both functional and structural components of social connection may help to identify the most isolated in society.
BMC medicine · 34 citationsread the source →
Discrimination and mental health among Somali refugee adolescents: the role of acculturation and gender.
This study examines the role of social identity (acculturation and gender) in moderating the association between discrimination and Somali adolescent refugees' mental health. Participants were English-speaking Somali adolescent refugees between the ages of 11 and 20 (N = 135). Perceived discrimination, trauma history, posttraumatic stress disorder (PTSD), depressive symptoms, and behavioral acculturation were assessed in structured interviews. Fourteen in-depth qualitative interviews and 3 focus groups were also conducted. Results indicated that discrimination was common and associated with worse mental health. For girls, greater Somali acculturation was associated with better mental health. Also, the association between discrimination and PTSD was less strong for girls who showed higher levels of Somali acculturation. For boys, greater American acculturation was associated with better mental health, and the association between discrimination and depression was less strong for boys with higher levels of American acculturation.
The American journal of orthopsychiatry · 69 citationsread the source →
Frequency of complementary and alternative medicine utilization in hypertensive patients attending an urban tertiary care centre in Nigeria.
Background: To study the frequency and pattern of use of complementary and alternative medicine (CAM) in patients with essential hypertension attending a tertiary hypertension clinic.
Methods: Two hundred and twenty-five consecutive hypertensive patients attending the hypertension clinic of the Lagos University Teaching Hospital over a 3-month period were interviewed. Socio-demographic data, duration of hypertension, clinic attendance, current blood pressure, and compliance to conventional medications was documented. CAM utilization was explored using both structured and open-ended questions.
Results: There were 90 (40%) male and 135 (60%) female patients with mean age +/- SD overall was 55.1 +/- 12.4 years. 88 (39.1%) of the respondents used CAM. Herbal products were the most commonly used CAM type. Amongst the CAM users, the most common herbal product used was garlic (69.3%). Others were native herbs (25%), ginger (23.9%), bitter leaf (Vernonia amygdalina) (9.1%), and aloe vera (4.5%). 2.5% used spiritual therapy. There was no difference in the clinical characteristics, socio-economic status, and blood pressure control of CAM users and non-users. Patients who utilized CAM had higher BMI compared with those who did not, but the difference was not statistically significant (mean BMI +/- SD of 29.1 +/- 5.6 vs 27.1 +/- 5.9 kg/m2; P = 0.05).
Conclusion: A significant proportion of hypertensive patients attending our tertiary facility and receiving conventional treatment also use CAM therapies. Clinicians need to be aware of this practice, understand the rationale for this health-seeking behaviour, proactively enquire about their use, and counsel patients regarding the potential of some of the therapies for adverse reactions and drug interactions.
BMC complementary and alternative medicine · 69 citationsread the source →
Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data.
Context: HIV patients treated with antiretroviral therapy (ART) often develop increased visceral adipose tissue (VAT).
Objective: Our objective was to perform a pooled analysis of two phase-3 studies of tesamorelin in ART-treated HIV patients with excess abdominal fat.
Design and setting: Two multicenter, international studies were conducted; a 26-wk randomized, placebo-controlled primary intervention phase was followed by a 26-wk safety extension.
Patients: A total of 806 ART-treated HIV patients with excess abdominal fat were randomized in a 2:1 fashion to receive tesamorelin 2 mg (n = 543) or placebo (n = 263) sc daily. At wk 26, patients initially on tesamorelin were rerandomized to 2 mg tesamorelin (T-T group, n = 246) or placebo (T-P, n = 135) for an additional 26 wk, whereas patients on placebo were switched to tesamorelin (P-T, n = 197).
Interventions: Tesamorelin (GHRH(1-44)) at a dose of 2 mg or identical placebo, sc, was given daily.
Main outcome measure: We evaluated percent change in VAT by computed tomography scan at wk 26.
Results: At wk 26, VAT decreased significantly in tesamorelin-treated patients (-24 +/- 41 vs. 2 +/- 35 cm(2), tesamorelin vs. placebo, P < 0.001; treatment effect, -15.4%). No significant changes were observed in abdominal sc adipose tissue (-2 +/- 32 vs. 2 +/- 29 cm(2), P = 0.08; treatment effect, -0.6%). Treatment with tesamorelin resulted in significant decreases in triglycerides (-37 +/- 139 vs. 6 +/- 112 mg/dl, P < 0.001; treatment effect, -12.3%) and cholesterol to high-density lipoprotein ratio (-0.18 +/- 1.00 vs. 0.18 +/- 0.94, P < 0.001; treatment effect, -7.2%) vs. placebo. Tesamorelin improved body image [belly appearance distress (P = 0.002)], patient rating of belly profile (P = 0.003), and physician rating of belly profile (P < 0.001). Mean IGF-I increased 108 +/- 112 vs.-7 +/- 64 ng/ml (P < 0.001 vs. placebo). At wk 52, decreases in VAT [-35 +/- 50 cm(2) (-17.5 +/- 23.3%)], waist circumference (-3.4 +/- 6.0 cm), triglycerides (-48 +/- 182 mg/dl), cholesterol (-8 +/- 38 mg/dl), and non-high-density lipoprotein (-7 +/- 38 mg/dl) were maintained (all P < 0.001 vs. original baseline) in the T-T group. Treatment with tesamorelin was generally well tolerated. No clinically meaningful differences were observed between groups in glucose parameters at wk 26 and 52.
Conclusions: Treatment with tesamorelin reduces VAT and maintains the reduction for up to 52 wk, preserves abdominal sc adipose tissue, improves body image and lipids, and is overall well tolerated without clinically meaningful changes in glucose parameters.
The Journal of clinical endocrinology and metabolism · 74 citationsread the source →