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Global patterns of mortality in international migrants: a systematic review and meta-analysis.

Background: 258 million people reside outside their country of birth; however, to date no global systematic reviews or meta-analyses of mortality data for these international migrants have been done. We aimed to review and synthesise available mortality data on international migrants. Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and Google Scholar databases for observational studies, systematic reviews, and randomised controlled trials published between Jan 1, 2001, and March 31, 2017, without language restrictions. We included studies reporting mortality outcomes for international migrants of any age residing outside their country of birth. Studies that recruited participants exclusively from intensive care or high dependency hospital units, with an existing health condition or status, or a particular health exposure were excluded. We also excluded studies limited to maternal or perinatal outcomes. We screened studies using systematic review software and extracted data from published reports. The main outcomes were all-cause and International Classification of Diseases, tenth revision (ICD-10) cause-specific standardised mortality ratios (SMRs) and absolute mortality rates. We calculated summary estimates using random-effects models. This study is registered with PROSPERO, number CRD42017073608. Findings: Of the 12 480 articles identified by our search, 96 studies were eligible for inclusion. The studies were geographically diverse and included data from all global regions and for 92 countries. 5464 mortality estimates for more than 15·2 million migrants were included, of which 5327 (97%) were from high-income countries, 115 (2%) were from middle-income countries, and 22 (<1%) were from low-income countries. Few studies included mortality estimates for refugees (110 estimates), asylum seekers (144 estimates), or labour migrants (six estimates). The summary estimate of all-cause SMR for international migrants was lower than one when compared with the general population in destination countries (0·70 [95% CI 0·65-0·76]; I2=99·8%). All-cause SMR was lower in both male migrants (0·72 [0·63-0·81]; I2=99·8%) and female migrants (0·75 [0·67-0·84]; I2=99·8%) compared with the general population. A mortality advantage was evident for refugees (SMR 0·50 [0·46-0·54]; I2=89·8%), but not for asylum seekers (1·05 [0·89-1·24]; I2=54·4%), although limited data was available on these groups. SMRs for all causes of death were lower in migrants compared with the general populations in the destination country across all 13 ICD-10 categories analysed, with the exception of infectious diseases and external causes. Heterogeneity was high across the majority of analyses. Point estimates of all-cause age-standardised mortality in migrants ranged from 420 to 874 per 100 000 population. Interpretation: Our study showed that international migrants have a mortality advantage compared with general populations, and that this advantage persisted across the majority of ICD-10 disease categories. The mortality advantage identified will be representative of international migrants in high-income countries who are studying, working, or have joined family members in these countries. However, our results might not reflect the health outcomes of more marginalised groups in low-income and middle-income countries because little data were available for these groups, highlighting an important gap in existing research. Our results present an opportunity to reframe the public discourse on international migration and health in high-income countries. Funding: Wellcome Trust, National Institute for Health Research, Medical Research Council, Alliance for Health Policy and Systems Research, Department for International Development, Fogarty International Center, Grand Challenges Canada, International Development Research Centre Canada, Inter-American Institute for Global Change Research, National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Mental Health, Swiss National Science Foundation, World Diabetes Foundation, UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, and European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group Research Funding for the ESCMID Study Group for Infections in Travellers and Migrants.

Lancet (London, England) · meta-analysis · 198 citationsread the source →

Interoception, alexithymia, and anxiety among individuals with alcohol use disorder.

Background: Interoception (i.e., the ability to recognize bodily signals), alexithymia (i.e., the inability to recognize emotional states) and negative affect (i.e., unpleasant feelings such as anxiety) have been associated with alcohol use disorder (AUD). Previous research suggests that interoception may underlie alexithymia, which in turn may be associated with negative affectivity. However, this remains to be empirically tested. This study investigates whether alexithymia mediates the association between interoception and anxiety and whether this association differs across individuals with AUD and a healthy control (HC) comparison group. Methods: The AUD group consisted of 99 participants enrolled in an 8-week abstinence-based inpatient treatment program. The HC group included 103 healthy individuals. The heartbeat counting task (HCT) was used to assess interoception (cardiac interoceptive accuracy). The Toronto Alexithymia Scale (TAS-20) was used to assess alexithymia. The Brief Symptom Inventory (BSI) was used to assess anxiety. Results: The moderated mediation model with interoception as the predictor, alexithymia as the mediator, and negative affect (i.e., state anxiety) as the dependent variable was tested. The analysis showed that the conditional indirect effect of interoception on anxiety via alexithymia was significant for individuals with AUD [ab = -0.300, bootstrap 95% CI = (-0.618, -0.088)], as well as for HCs [ab = -0.088, bootstrap 95% CI = (-0.195, -0.014)]; however, the conditional indirect effect significantly differed across HCs and individuals with AUD. Namely, the mediated effect was greater among individuals with AUD compared to the HC group. Conclusion: The results suggests that interoceptive impairment contributes to greater negative affect (i.e., state anxiety) via alexithymia especially for individuals with AUD. Improving emotion recognition via therapeutic methods focused on strengthening interoceptive abilities could improve outcomes for individuals receiving treatment for AUD.

Frontiers in psychiatry · 5 citationsread the source →

Circumcision devices versus standard surgical techniques in adolescent and adult male circumcisions.

Background: Medical circumcisions are among the most common surgical procedures performed in males. The usual indications are phimosis (inability to completely retract the foreskin and expose the glans due to a congenital or acquired constriction of the prepuce), paraphimosis (when the foreskin is not pulled back over the glans after retraction resulting in a tight constricting band which causes swelling of the distal penis and acute discomfort), balanoposthitis (erythema and edema of the prepuce and glans) and balanitis (inflammation is confined to the glans; the foreskin is usually non-retractile). Circumcision devices have been developed to shorten the operative time, simplify techniques, and improve safety and cosmetic outcomes. The devices generally aim to crush the foreskin while simultaneously creating hemostasis, the foreskin is then excised or allowed to slough off. Their use is supposedly safer and easier to replicate than the standard dissection techniques. There are at least 20 devices for male circumcision on the market, yet their effectiveness has not been reviewed to date. Objectives: To assess the effects of device-based circumcisions compared with standard surgical techniques in adolescent and adult males (10 years old and above). Search methods: We performed a comprehensive search with no restrictions to the language of publication or publication status. We searched the Cochrane Library, MEDLINE (PubMed), Embase, Web of Science, trials registries, grey literature sources and conference proceedings up to 16 April 2020. Selection criteria: We included randomized controlled trials of device-based circumcisions (crush or ligature circumcision devices) compared to standard surgical dissection-based circumcision conducted by health professionals in a medical setting. Data collection and analysis: At least two review authors independently assessed study eligibility and extracted data from the included studies. We classified adverse events into serious, moderate or mild. We reported study results as risk ratios (RR) or mean differences (MD) using 95% confidence intervals (CI) and a random-effects model. We used the GRADE approach to evaluate the overall certainty of the evidence for each outcome. Main results: Eighteen trials met the inclusion criteria. Trials were conducted in China, South Africa, Kenya and Zambia, Mozambique, Rwanda, Uganda and Zimbabwe. Primary outcomes Serious adverse events: there were no serious adverse events in either treatment arm (11 trials, 3472 participants). Moderate adverse events: there may be a slight increase in moderate adverse events when devices are used compared to standard surgical techniques (RR 1.31, 95% CI 0.55 to 3.10; I²= 68%; 10 trials, 3370 participants; low-certainty evidence); this corresponds to 8 more (ranging from 15 fewer to 84 more) moderate adverse events per 1000 participants. We downgraded the certainty of the evidence for study limitations and imprecision. Secondary outcomes Mild adverse events: we are uncertain about the difference in mild adverse events between groups when devices are used compared to standard surgical techniques (RR 1.09, 95% CI 0.44 to 2.72; I² = 91%; 10 trials, 3370 participants; very low-certainty evidence). We downgraded the certainty of the evidence for study limitations, imprecision and unexplained inconsistency. Operative time: operative time is probably about 17 minutes shorter when using a device rather than standard surgical techniques, which constitutes a clinically meaningful decrease in a procedure (MD -17.26 minutes, 95% CI -19.96 to -14.57; I² = 99%; 14 trials, 4812 participants; moderate-certainty evidence). We downgraded the certainty of the evidence for serious study limitations. The standard surgical technique generally takes about 24 minutes. There may be less postoperative pain during the first 24 hours when circumcision devices are used compared to standard surgical techniques (measured using a visual analog scale [VAS]; MD 1.30 cm lower, 95% CI 2.37 lower to 0.22 lower; I² = 99%; 9 trials, 3022 participants; low-certainty evidence). We downgraded the certainty of the evidence for study limitations and unexplained heterogeneity. There may be little or no difference in postoperative pain experienced during the first seven days when compared with standard surgical techniques (measured using a VAS; MD 0.11 cm higher, 95% CI 0.89 lower to 1.11 higher; I² = 94%; 4 trials, 1430 participants; low-certainty evidence). We downgraded the certainty of the evidence for study limitations and unexplained inconsistency. A higher score on the VAS indicates greater pain. Participants may slightly prefer circumcision devices compared to standard surgical techniques (RR 1.19, 95% CI 1.04 to 1.37; I² = 97%; 15 trials, 4501 participants; low-certainty evidence). We downgraded the certainty of the evidence for study limitations and unexplained inconsistency. We recorded satisfaction as a dichotomous outcome. Higher rates reflected greater satisfaction. Authors' conclusions: We found that there were no serious adverse events reported when using a circumcision device compared to standard surgical techniques, but they may slightly increase moderate adverse effects, and it is unclear whether there is a difference in mild adverse effects. Use of circumcision devices probably reduces the time of the procedure by about 17 minutes, a clinically meaningful time saving. For patients, use of the circumcision device may result in lower pain scores during the first 24 hours and patients may be slightly more satisfied with it compared with standard surgical techniques. Clinicians, patients and policymakers can use these results in conjunction with their own contextual factors to inform the approach that best suits their healthcare settings. High-quality trials evaluating this intervention are needed to provide further certainty regarding the rates of adverse effects and postoperative pain of using devices compared to standard approaches.

The Cochrane database of systematic reviews · meta-analysis · 15 citationsread the source →

Antidepressants for people with epilepsy and depression.

Background: Depressive disorders are the most common psychiatric comorbidity in people with epilepsy, affecting around one-third, with a significant negative impact on quality of life. There is concern that people may not be receiving appropriate treatment for their depression because of uncertainty regarding which antidepressant or class works best, and the perceived risk of exacerbating seizures. This review aimed to address these issues, and inform clinical practice and future research. This is an updated version of the original Cochrane Review published in Issue 12, 2014. Objectives: To evaluate the efficacy and safety of antidepressants in treating depressive symptoms and the effect on seizure recurrence, in people with epilepsy and depression. Search methods: For this update, we searched CRS Web, MEDLINE, SCOPUS, PsycINFO, and ClinicalTrials.gov (February 2021). We searched the World Health Organization Clinical Trials Registry in October 2019, but were unable to update it because it was inaccessible. There were no language restrictions. Selection criteria: We included randomised controlled trials (RCTs) and prospective non-randomised studies of interventions (NRSIs), investigating children or adults with epilepsy, who were treated with an antidepressant and compared to placebo, comparative antidepressant, psychotherapy, or no treatment for depressive symptoms.  DATA COLLECTION AND ANALYSIS: The primary outcomes were changes in depression scores (proportion with a greater than 50% improvement, mean difference, and proportion who achieved complete remission) and change in seizure frequency (mean difference, proportion with a seizure recurrence, or episode of status epilepticus). Secondary outcomes included the number of participants who withdrew from the study and reasons for withdrawal, quality of life, cognitive functioning, and adverse events. Two review authors independently extracted data for each included study. We then cross-checked the data extraction. We assessed risk of bias using the Cochrane tool for RCTs, and the ROBINS-I for NRSIs. We presented binary outcomes as risk ratios (RRs) with 95% confidence intervals (CIs) or 99% CIs for specific adverse events. We presented continuous outcomes as standardised mean differences (SMDs) with 95% CIs, and mean differences (MDs) with 95% CIs.  MAIN RESULTS: We included 10 studies in the review (four RCTs and six NRSIs), with 626 participants with epilepsy and depression, examining the effects of antidepressants. One RCT was a multi-centre study comparing an antidepressant with cognitive behavioural therapy (CBT). The other three RCTs were single-centre studies comparing an antidepressant with an active control, placebo, or no treatment. The NRSIs reported on outcomes mainly in participants with focal epilepsy before and after treatment for depression with a selective serotonin reuptake inhibitor (SSRI); one NRSI compared SSRIs to CBT.  We rated one RCT at low risk of bias, three RCTs at unclear risk of bias, and all six NRSIs at serious risk of bias. We were unable to conduct any meta-analysis of RCT data due to heterogeneity of treatment comparisons. We judged the certainty of evidence to be moderate to very low across comparisons, because single studies contributed limited outcome data, and because of risk of bias, particularly for NRSIs, which did not adjust for confounding variables. More than 50% improvement in depressive symptoms ranged from 43% to 82% in RCTs, and from 24% to 97% in NRSIs, depending on the antidepressant given. Venlafaxine improved depressive symptoms by more than 50% compared to no treatment (mean difference (MD) -7.59 (95% confidence interval (CI) -11.52 to -3.66; 1 study, 64 participants; low-certainty evidence); the results between other comparisons were inconclusive. Two studies comparing SSRIs to CBT reported inconclusive results for the proportion of participants who achieved complete remission of depressive symptoms.  Seizure frequency data did not suggest an increased risk of seizures with antidepressants compared to control treatments or baseline. Two studies measured quality of life; antidepressants did not appear to improve quality of life over control. No studies reported on cognitive functioning. Two RCTs and one NRSI reported comparative data on adverse events; antidepressants did not appear to increase the severity or number of adverse events compared to controls. The NSRIs reported higher rates of withdrawals due to adverse events than lack of efficacy. Reported adverse events for antidepressants included nausea, dizziness, sedation, headache, gastrointestinal disturbance, insomnia, and sexual dysfunction.  AUTHORS' CONCLUSIONS: Existing evidence on the effectiveness of antidepressants in treating depressive symptoms associated with epilepsy is still very limited. Rates of response to antidepressants were highly variable. There is low certainty evidence from one small RCT (64 participants) that venlafaxine may improve depressive symptoms more than no treatment; this evidence is limited to treatment between 8 and 16 weeks, and does not inform longer-term effects. Moderate to low evidence suggests neither an increase nor exacerbation of seizures with SSRIs.  There are no available comparative data to inform the choice of antidepressant drug or classes of drug for efficacy or safety for treating people with epilepsy and depression. RCTs of antidepressants utilising interventions from other treatment classes besides SSRIs, in large samples of patients with epilepsy and depression, are needed to better inform treatment policy. Future studies should assess interventions across a longer treatment duration to account for delayed onset of action, sustainability of treatment responses, and to provide a better understanding of the impact on seizure control.

The Cochrane database of systematic reviews · meta-analysis · 30 citationsread the source →

Mental health of migrants with pre-migration exposure to armed conflict: a systematic review and meta-analysis.

Background: Exposure to armed conflict has been associated with negative mental health consequences. We aimed to estimate the prevalence of generalised anxiety disorder, major depressive disorder, and post-traumatic stress disorder among migrants exposed to armed conflict. Methods: In this systematic review and meta-analysis, we searched online databases (Cochrane Library, Embase, LILACS, PsycInfo [via Ovid], PubMed, and Web of Science Core Collection) for relevant observational studies published between Jan 1, 1994, and June 28, 2021. We included studies that used standardised psychiatric interviews to assess generalised anxiety disorder, major depressive disorder, or post-traumatic stress disorder among migrants (refugees or internally displaced persons; aged ≥18 years) with pre-migration exposure to armed conflict. We excluded studies in which exposure to armed conflict could not be ascertained, studies that included a clinical population or people with chronic diseases that can trigger the onset of mental disease, and studies published before 1994. We used a random effects model to estimate each mental health disorder's pooled prevalence and random effects meta-regression to assess sources of heterogeneity. Two independent reviewers assessed the risk of bias for each study using the Joanna Briggs Institute Checklist for Prevalence Studies. The protocol was registered with PROSPERO, CRD42020209251. Findings: Of the 13 935 studies identified, 34 met our inclusion criteria; these studies accounted for 15 549 migrants. We estimated a prevalence of current post-traumatic stress disorder of 31% (95% CI 23-40); prevalence of current major depressive disorder of 25% (17-34); and prevalence of generalised anxiety disorder of 14% (5-35). Younger age was associated with a higher prevalence of current post-traumatic stress disorder (odds ratio 0·95 [95% CI 0·90-0·99]), lifetime post-traumatic stress disorder (0·88 [0·83-0·92]), and current generalised anxiety disorder (0·87 [0·78-0·97]). A longer time since displacement was associated with a lower lifetime prevalence of post-traumatic stress disorder (0·88 [0·81-0·95]) and major depressive disorder (0·81 [0·77-0·86]). Migrating to a middle-income (8·09 [3·06-21·40]) or low-income (39·29 [11·96-129·70]) country was associated with increased prevalence of generalised anxiety disorder. Interpretation: Migrants who are exposed to armed conflict are at high risk of mental health disorders. The mental health-care needs of migrants should be assessed soon after resettlement, and adequate care should be provided, with particular attention paid to young adults. Funding: Marie Skłodowska-Curie Actions (Horizon 2020-COFUND), MinCiencias (Colombia), and Swiss National Science Foundation.

The Lancet. Public health · meta-analysis · 111 citationsread the source →

Does Improving Medical Record Documentation Better Reflect Severity of Illness in Neurosurgical Patients?

Physician documentation in the medical record is essential for communicating the clinical status and care plan to other healthcare providers. The medical record also serves as a medicolegal document to protect the physician should medical malpractice be alleged. In addition to these uses, documentation of patients' diagnoses and procedures is used by hospital coders to calculate severity of illness (SOI) and risk of mortality (ROM) ratings. A rating given from level 1 to 4 (4 being most severe), SOI reflects a patient's degree of physiological illness. Also scored from 1 to 4, ROM is a gauge of the patient's risk of death while in the hospital on the basis of the patient's diagnoses (Table 1).TABLE: 1. Severity of Illness and Risk of Mortality Grading SystemsBoth SOI and ROM have significant roles in healthcare economics. Hospital reimbursement depends in part on SOI. The Centers for Medicare and Medicaid Services (CMS) is the entity of the federal government that is responsible for healthcare financing, coverage, and payment of Medicare and Medicaid beneficiaries. Formerly known as the Health Care Financing Administration, CMS adopted diagnosis-related groups (DRGs) in 1983 after their development at Yale University in 1970. Their purpose was to replace the traditional per-diem method of hospital reimbursement. Per diems were cost based and characterized as an undifferentiated patient day regardless of patient illness. In contrast, each DRG classification represents similar resource consumption and length-of-stay patterns so that reimbursement is based on these expectations. In 2008, the CMS went one step further and added a severity-adjusted version to the original DRGs called Medicare-severity DRG.1 The severity adjustment takes into account the patient's SOI and is now used by the Medicare Inpatient Prospective Payment System. The SOI and ROM scores are also being used to gauge quality control issues. Data for every Medicare inpatient stay are maintained in the Medicare Provider and Analysis Review file.2 Quality improvement organizations contracted by CMS to provide quality oversight to Medicare providers use the data to assess potential problems with noncompliance. Additionally, these organizations analyze a facility's Medicare-severity DRG mix to look for problems with hospitals that may potentially always code for higher-weighted DRGs and appear as outliers compared with other similar facilities.3 Finally, “quality of care” assessments use SOI and ROM. Mortality rates vary between providers and hospitals; the presumption is that after controlling for patients' severity of illness, residual differences in mortality rates relate to differences in quality of care. Corporations such as Thompson Reuters have created a marketing tool and “status” based on this information that hospitals may strive to achieve. The well-known “Top 100 Hospitals”4 lists the 100 “best” hospitals across the country in a given specialty line. When the results of the Hospital Consumer Assessment of Healthcare Providers and Systems survey5 are compared between winners of the Top 100 Hospitals award and nonwinners, the award winners do slightly better than nonwinners on all survey items that showed modest but statistically significant differences between the 2 groups.6 These findings suggest that marketing tools such as the Top 100 Hospitals might play a role in consumer perception, assessment, and decision making. All-patient-refined DRGs (APR-DRGs) are another mode for comparison. Trademarked by 3M, APR-DRGs classify all inpatient admissions based on the SOI and ROM levels represented by International Classification of Disease, ninth revision (ICD-9), codes. Institutions such as the Agency for Healthcare Research and Quality are using APR-DRGs for quality monitoring purposes, especially for severity adjustment of mortality rates.1 The SOI and ROM are derived from documentation of patients' diagnoses and comorbidities.1,7 Errors in documentation can lead to overestimation or underestimation of expected mortality, which has an effect on an institution's comparison with other hospitals.8,9 Furthermore, neurosurgeons contribute significantly to hospitals' financial health.10,11 Better documentation of admitting diagnoses and comorbidities should enable more accurate ICD-9 coding, which in turn should lead to more accurate calculation of SOI and ROM. The rationale for the study stemmed from a need for resident participation in a quality improvement project, a requirement dictated by the Accreditation Council of Graduate Medical Education.12 Before the project, a preliminary review of progress notes on the neurosurgery service by one of the authors (N.S.L.) indicated suboptimal documentation of patient comorbidities. The objective of this study was to determine whether interventions designed to effectively improve physician clinical documentation would subsequently lead to increased capture of SOI and ROM. A secondary aim of the project was to simultaneously provide residents with a quality improvement opportunity. We hypothesize that the multimodality interventions that improve neurosurgeons' clinical documentation lead to better characterization of SOI and ROM. MATERIALS AND METHODS Documentation Improvement Interventions Before data collection, 3 specific interventions were used to educate physicians with the goal of improving medical record documentation as part of the master's thesis of one of the authors (C.H.). These modalities included the following: group in-service, development and use of a progress note template, and concurrent medical record coder review and feedback to the physician during the patients' in-hospital stays. Faculty and residents in the Division of Neurological Surgery at University of Missouri Hospitals and Clinics participated in a 30-minute in-service on coding, SOI, and ROM. A new neurosurgery progress note template (Figure 1) was introduced, and instructions for its use were provided. The template was organized to include comorbidities listed as ICD-9 codes and grouped into organ system for ease of location.FIGURE 1: Neurosurgery progress note. Mechanisms for queries to the physicians from the nurse reviewer and appropriate responses were explained to the group. Informed consent was obtained from the participating physicians. The study was approved by the Health Sciences Institutional Review Board. After the in-service, a nurse-reviewer (working in the capacity of assistant manager of medical records) began random review of neurosurgical patient records. Random record review was performed 2 to 3 times per week, averaging 10 to 15 h/wk, while patients were still hospitalized to look for potential diagnoses that were not appropriately documented. Charts for review were chosen at random; however, intensive care unit patients were given priority for review over floor patients. Information gathered was kept on a worksheet (Figure 2), and cases for which questions existed were e-mailed to the physicians with a copy to the senior author (N.S.L). A typical query follows: “Patient X, MNICU 13, had a 3400cc EBL during OR, and received several units of PRBCx and FFP. H&H dropped from 12.1/35.2 to 5.9/17. Would a secondary diagnosis of acute blood loss anemia be appropriate? If so, please document in the progress notes.”FIGURE 2: Clinical documentation review tool. Follow-up on queries was completed to determine whether the physician had documented the diagnosis in question. If no response was made, a second e-mail was sent. In cases when the patient had been discharged and confirmation or disagreement with the query was not documented in the progress notes as requested, an e-mail notification was sent, asking the physician to address the query in the discharge summary. This method of review, queries by e-mail, and rereview occurred for 8 weeks. Data Collection All neurosurgery service adult in-patient charts at University of Missouri Hospital and Clinics were retrospectively reviewed from 3 time intervals. June 2004 to December 2004 represented the preintervention period. August 2007 to December 2007 was the time period during active educational intervention. Finally, June 2008 to December 2008 represented the postintervention period. Data collected included patient age, sex, ICD-9 diagnoses, raw patient mortality, SOI, and ROM. Patients younger than 18 years of age at the time of admission were excluded. Versions 24 and 25 of the 3M APR-DRGs13,14 were used to calculate ROM and SOI. Preliminary data were pulled from each time period and analyzed according to the description below. From the results of the preliminary data analysis, the standard deviation for the SOI and ROM outcomes was estimated to be about 1.0 units. It was determined that sample sizes of 300 patients per time period would give well over 80% power for detecting differences in mean scores of 0.25 units. The estimated power was found using the POWER procedure in SAS version 9 (SAS Institute Inc, Cary, North Carolina). Data Analysis The outcomes of mortality, SOI, and ROM can all be influenced by a patient's age, sex, and primary diagnosis. Consequently, analyses were done to determine whether any of these variables differed between time periods. Furthermore, these variables were considered covariates when testing the primary outcomes for differences between time periods. Primary diagnoses were grouped into 9 categories based on ICD-9 codes as follows: malignant neoplasms, benign neoplasms, nervous system disorders, cardiovascular disease, musculoskeletal disorders, skull/spine injuries, brain contusions, complications, and other diagnoses. The Kruskal-Wallis test was used to test for differences in age between time periods. Sex differences were assessed with a χ2 model. Stratification or adjustment for differences in age and sex was performed with the Cochran-Mantel-Haenszel test. For the prediction of the probability of occurrence of mortality, logistic regression was used. Finally, the cumulative logit model was used to analyze SOI and ROM, taking into account differences in primary diagnoses over time. The SAS Analytical Software version 9.0 was used for the analysis. In view of the fact that preliminary data were reanalyzed, allowing 2 opportunities to reject the null hypothesis of no group differences, only values of P < .01 were considered significant. RESULTS Chart Review Intervention During the 8-week period of chart review, 53 inpatient charts were reviewed. A total of 99 reviews were completed in total, with 41 queries sent to physicians (41%). All but 2 queries were sent via e-mail. Sixteen second-request queries were sent. Twenty queries (53%) were agreed on and documented in the record. A physician disagreed with 1 query, so no change in documentation was made, and 17 queries yielded no response (44.7%). SOI/ROM Values Over the 3 time periods, 1009 cases were analyzed: 329 patients during the preintervention period, 306 patients during the intervention period, and 374 patients during the post-intervention period. The simple mean values of SOI in the 3 time periods were as follows: 1.72 before intervention, 1.69 during intervention, and 1.82 after intervention (P = .09, χ2). Simple mean values of ROM in each time period were 1.40, 1.43, and 1.56 respectively (P = .02, χ2), with mortality rates of 6.38%, 3.59%, and 5.61% respectively (P = .27, χ2). Raw data results are summarized in Table 2.TABLE: 2. Summary of Raw DataaEffect of Age and Sex on SOI and ROM Mean patient age differed significantly between time periods: 48.3 years of age before intervention, 52.1 years of age during intervention, and 53.1 years of age after intervention (P = .001, Kruskal-Wallis). Accounting for differences in age did not affect SOI (P = .24), ROM (P = .48), and raw mortality (P = .06, Cochran-Mantel-Haenszel). Sex distributions were similar in each time period (P = .64, χ2). Effect of Diagnosis The distribution of diagnoses in each time period is shown in Table 3. Primary diagnosis did not differ significantly between the preintervention and intervention time periods (P = .13), even when adjusted for age and sex (P = .28, Cochran-Mantel-Haenszel). However, when the preintervention and intervention periods were combined and compared with the postintervention period, differences in diagnoses were noted (P < .001, Cochran-Mantel-Haenszel).TABLE: 3. Distributions of Diagnoses Between 3 Time PeriodsIn an effort to account for differences in diagnoses, a statistical compromise had to be achieved between not using primary diagnoses as a covariant and using them with a large number of categories. Therefore, 3 categories were established on the basis of the diagnosis frequency: cardiovascular disease (32 deaths), brain contusion (6 deaths), and other (15 deaths). After diagnosis differences (3 categories) were accounted for with logistic regression, no differences in mortality rate were found between the postintervention period and either the intervention (P = .08) or preintervention (P = .15) period. No significant differences between preintervention and postinterventional periods for SOI (P = .29) or ROM (P = .48) were present when differences in diagnoses were accounted for (cumulative logit model). DISCUSSION Overall, we expected SOI to be lower during the preintervention period and the ROM modified by SOI to be lower during the intervention and postintervention periods. However, despite interventions such as educational in-service, progress note template, and reminders about the possibility of addending progress notes, no differences in SOI or ROM were present during active intervention or in the period after intervention. The lack of impact of intervention on SOI and ROM was not affected by the differences in age or diagnoses present among the 3 time periods. Other studies have shown success with progress note templates. Grogan et al15 focused on improvements to physician documentation and evaluated the effectiveness in terms of ICD-9 coding, APR-DRG, DRG weight, and University Healthcare Consortium-predicted mortality. A progress note template included a section developed by coding specialists with 40 of the most common general surgery comorbidities and complications (in check-box format). A significant increase was found in total ICD-9 codes, template-specific ICD-9 codes, APR-DRG, DRG weight, and University Healthcare Consortium-predicted mortality. Sprtel and Zlabek16 also showed success with the implementation of a progress note template in conjunction with a brief documentation lecture. Their results showed an absolute increase in the highest code by 14.5%, increased billable income by $10 385, and improved resident awareness of documentation. A number of interventions for improvement in documentation and assessment end points have been suggested. Marco and Buchman17 noted that simply asking for private commitment to change can yield measurable results. They obtained in writing acknowledgement that improvement in documentation was necessary and noticed that the acknowledging physicians showed improvement in the percentage of cases with the required documentation over time. As-Sanie et al18 had success with obstetrics/gynecology residents after providing individual instructional sessions with faculty on coding and documentation, whereas Lemen19 also showed success within the same specialty with the assistance of an online module. At the other end of the spectrum, Tinsley20 described the use of a whole multidisciplinary team to improve documentation among psychiatry residents. The team met regularly to clarify resident charting responsibilities, to make the inpatient record a better communication tool, and to consider the various causes of charting deficiencies. Improvement in charting 4 of 5 items (admission note, an off-service note, descriptions of medication changes, daily progress notes, and the name and discipline of the individual recording these items) improved significantly after 1 month of intervention and was maintained at 6 months. Table 4 summarizes these intervention results.TABLE: 4. Summary of Literature ReviewaTime is likely necessary to establish educational interventions that generate long-lasting habits in physicians and improve documentation. Relationships are present between repetition and automaticity of such habits. For instance, in 1 study,33 82 mostly postgraduate students were asked to choose a healthy eating, drinking, or exercise behavior to convert into a daily habit. A self-report habit index34 was used to quantify habit strength. During 12 weeks of active study, 48% of participants reached levels thought to be consistent with habit formation. Further analysis concluded that the time needed for participants to reach 95% of their automaticity ranged from 18 to 254 days (mean, 64 days). The 8 weeks of active intervention in this study may not have been sufficient to allow documentation habits to form fully. Furthermore, educators must also question whether the amount of time required to learn simple habits differs from more complex habits requiring additional planning. Verplanken35 showed that when repetitions are limited, a simple behavior had a higher habit score than a complex behavior. Physician documentation in the setting of demanding schedules and the intricacies of medical coding likely falls into the category of a complex habit. Therefore, physicians' documentation habits promoting better documentation may be on the longer end of the to The effect the number of daily repetitions on the time to automaticity is also This study other that may improvement in documentation. did not to of queries with documentation The physicians would not be to their e-mail in the day or and progress note were not Additionally, physicians may have that an or new note in the medical record for the purpose of to a query was given their other A more of review and physician feedback have to an increase in in the medical record. and medical for diagnoses that were and not appropriately documented is a Over the 8 weeks of the intervention period, 99 reviews on 53 charts were Therefore, of the total neurosurgical admissions during the 8-week period, only of them were reviewed at during their For review and more nurse-reviewer might be required to review a of inpatient charts before significant results can be in improving documentation be that the progress note template was progress note was from Grogan et was modified by a multidisciplinary the of neurosurgical and the assistant manager of medical to include complications and comorbidities typical of neurosurgical patients. No studies were to the of the template in accurate diagnoses. the educational interventions improved medical record documentation, SOI and ROM may not have differed between the 3 time periods for other This study did not assess the level and of the medical Medical coders are by to them on can and codes However, a is required to review and to the clinical between various and common complications with specific for the to documentation to look Documentation of comorbidities and complications on a progress note template might provide more documentation but not more accurate must also consider whether ICD-9 codes are appropriate for SOI and ROM. have found of in codes, on the diagnoses and being After a review of medical from et concluded that coding of diagnosis had an rate of compared with medical record et the of codes for cardiovascular and risk Overall, in Medicare the of codes was whereas the ranged from only to the ICD-9 data to illness, other studies have shown that these can is in disease and For instance, et and the of Health found that an illness of ICD-9 data from a in the with from and ICD-9 codes have been found in of disease to be for is not known whether the same can be for using ICD-9 codes to calculate of SOI and ROM. Interventions to improve documentation by physicians to change SOI or ROM in patients on a neurosurgical these interventions were to make a or coders a amount of and to at documentation to look to improve their quality in to SOI and ROM must be to time and to the of the of these physicians should play an active role in the development and of educational such as physician feedback and chart review all patients on the inpatient service may lead to a more medical record documentation. for this project was by the Division of Neurological Surgery Research The authors have no financial or in any of the or described in this This was based in part on the 2007 master's thesis project by for the University of Missouri Health and are Interventions for Physician Documentation of Severity of Illness and Risk of We to of University of Missouri for assistance with the statistical analysis. We also to for

Neurosurgery · 11 citationsread the source →

Behavioural and cognitive-behavioural interventions for outwardly directed aggressive behaviour in people with intellectual disabilities.

Background: Outwardly directed aggressive behaviour in people with intellectual disabilities is a significant issue that may lead to poor quality of life, social exclusion and inpatient psychiatric admissions. Cognitive and behavioural approaches have been developed to manage aggressive behaviour but the effectiveness of these interventions on reducing aggressive behaviour and other outcomes are unclear. This is the third update of this review and adds nine new studies, resulting in a total of 15 studies in this review. Objectives: To evaluate the efficacy of behavioural and cognitive-behavioural interventions on outwardly directed aggressive behaviour compared to usual care, wait-list controls or no treatment in people with intellectual disability. We also evaluated enhanced interventions compared to non-enhanced interventions. Search methods: We used standard, extensive Cochrane search methods. The latest search date was March 2022. We revised the search terms to include positive behaviour support (PBS). Selection criteria: We included randomised and quasi-randomised trials of children and adults with intellectual disability of any duration, setting and any eligible comparator. Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were change in 1. aggressive behaviour, 2. ability to control anger, and 3. adaptive functioning, and 4. Adverse effects: Our secondary outcomes were change in 5. mental state, 6. medication, 7. care needs and 8. quality of life, and 9. frequency of service utilisation and 10. user satisfaction data. We used GRADE to assess certainty of evidence for each outcome. We expressed treatment effects as mean differences (MD) or odds ratios (OR), with 95% confidence intervals (CI). Where possible, we pooled data using a fixed-effect model. Main results: This updated version comprises nine new studies giving 15 included studies and 921 participants. The update also adds new interventions including parent training (two studies), mindfulness-based positive behaviour support (MBPBS) (two studies), reciprocal imitation training (RIT; one study) and dialectical behavioural therapy (DBT; one study). It also adds two new studies on PBS. Most studies were based in the community (14 studies), and one was in an inpatient forensic service. Eleven studies involved adults only. The remaining studies involved children (one study), children and adolescents (one study), adolescents (one study), and adolescents and adults (one study). One study included boys with fragile X syndrome. Six studies were conducted in the UK, seven in the USA, one in Canada and one in Germany. Only five studies described sources of funding. Four studies compared anger management based on cognitive behaviour therapy to a wait-list or no treatment control group (n = 263); two studies compared PBS with treatment as usual (TAU) (n = 308); two studies compared carer training on mindfulness and PBS with PBS only (n = 128); two studies involving parent training on behavioural approaches compared to wait-list control or TAU (n = 99); one study of mindfulness to a wait-list control (n = 34); one study of adapted dialectal behavioural therapy compared to wait-list control (n = 21); one study of RIT compared to an active control (n = 20) and one study of modified relaxation compared to an active control group (n = 12). There was moderate-certainty evidence that anger management may improve severity of aggressive behaviour post-treatment (MD -3.50, 95% CI -6.21 to -0.79; P = 0.01; 1 study, 158 participants); very low-certainty evidence that it might improve self-reported ability to control anger (MD -8.38, 95% CI -14.05 to -2.71; P = 0.004, I2 = 2%; 3 studies, 212 participants), adaptive functioning (MD -21.73, 95% CI -36.44 to -7.02; P = 0.004; 1 study, 28 participants) and psychiatric symptoms (MD -0.48, 95% CI -0.79 to -0.17; P = 0.002; 1 study, 28 participants) post-treatment; and very low-certainty evidence that it does not improve quality of life post-treatment (MD -5.60, 95% CI -18.11 to 6.91; P = 0.38; 1 study, 129 participants) or reduce service utilisation and costs at 10 months (MD 102.99 British pounds, 95% CI -117.16 to 323.14; P = 0.36; 1 study, 133 participants). There was moderate-certainty evidence that PBS may reduce aggressive behaviour post-treatment (MD -7.78, 95% CI -15.23 to -0.32; P = 0.04, I2 = 0%; 2 studies, 275 participants) and low-certainty evidence that it probably does not reduce aggressive behaviour at 12 months (MD -5.20, 95% CI -13.27 to 2.87; P = 0.21; 1 study, 225 participants). There was low-certainty evidence that PBS does not improve mental state post-treatment (OR 1.44, 95% CI 0.83 to 2.49; P = 1.21; 1 study, 214 participants) and very low-certainty evidence that it might not reduce service utilisation at 12 months (MD -448.00 British pounds, 95% CI -1660.83 to 764.83; P = 0.47; 1 study, 225 participants). There was very low-certainty evidence that mindfulness may reduce incidents of physical aggression (MD -2.80, 95% CI -4.37 to -1.23; P < 0.001; 1 study; 34 participants) and low-certainty evidence that MBPBS may reduce incidents of aggression post-treatment (MD -10.27, 95% CI -14.86 to -5.67; P < 0.001, I2 = 87%; 2 studies, 128 participants). Reasons for downgrading the certainty of evidence were risk of bias (particularly selection and performance bias); imprecision (results from single, often small studies, wide CIs, and CIs crossing the null effect); and inconsistency (statistical heterogeneity). Authors' conclusions: There is moderate-certainty evidence that cognitive-behavioural approaches such as anger management and PBS may reduce outwardly directed aggressive behaviour in the short term but there is less certainty about the evidence in the medium and long term, particularly in relation to other outcomes such as quality of life. There is some evidence to suggest that combining more than one intervention may have cumulative benefits. Most studies were small and there is a need for larger, robust randomised controlled trials, particularly for interventions where the certainty of evidence is very low. More trials are needed that focus on children and whether psychological interventions lead to reductions in the use of psychotropic medications.

The Cochrane database of systematic reviews · systematic review · 6 citationsread the source →

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 →

Dialectical behavior therapy for high suicide risk in individuals with borderline personality disorder: a randomized clinical trial and component analysis.

Importance: Dialectical behavior therapy (DBT) is an empirically supported treatment for suicidal individuals. However, DBT consists of multiple components, including individual therapy, skills training, telephone coaching, and a therapist consultation team, and little is known about which components are needed to achieve positive outcomes. Objective: To evaluate the importance of the skills training component of DBT by comparing skills training plus case management (DBT-S), DBT individual therapy plus activities group (DBT-I), and standard DBT which includes skills training and individual therapy. Design, setting, and participants: We performed a single-blind randomized clinical trial from April 24, 2004, through January 26, 2010, involving 1 year of treatment and 1 year of follow-up. Participants included 99 women (mean age, 30.3 years; 69 [71%] white) with borderline personality disorder who had at least 2 suicide attempts and/or nonsuicidal self-injury (NSSI) acts in the last 5 years, an NSSI act or suicide attempt in the 8 weeks before screening, and a suicide attempt in the past year. We used an adaptive randomization procedure to assign participants to each condition. Treatment was delivered from June 3, 2004, through September 29, 2008, in a university-affiliated clinic and community settings by therapists or case managers. Outcomes were evaluated quarterly by blinded assessors. We hypothesized that standard DBT would outperform DBT-S and DBT-I. Interventions: The study compared standard DBT, DBT-S, and DBT-I. Treatment dose was controlled across conditions, and all treatment providers used the DBT suicide risk assessment and management protocol. Main outcomes and measures: Frequency and severity of suicide attempts and NSSI episodes. Results: All treatment conditions resulted in similar improvements in the frequency and severity of suicide attempts, suicide ideation, use of crisis services due to suicidality, and reasons for living. Compared with the DBT-I group, interventions that included skills training resulted in greater improvements in the frequency of NSSI acts (F1,85 = 59.1 [P < .001] for standard DBT and F1,85 = 56.3 [P < .001] for DBT-S) and depression (t399 = 1.8 [P = .03] for standard DBT and t399 = 2.9 [P = .004] for DBT-S) during the treatment year. In addition, anxiety significantly improved during the treatment year in standard DBT (t94 = -3.5 [P < .001]) and DBT-S (t94 = -2.6 [P = .01]), but not in DBT-I. Compared with the DBT-I group, the standard DBT group had lower dropout rates from treatment (8 patients [24%] vs 16 patients [48%] [P = .04]), and patients were less likely to use crisis services in follow-up (ED visits, 1 [3%] vs 3 [13%] [P = .02]; psychiatric hospitalizations, 1 [3%] vs 3 [13%] [P = .03]). Conclusions and relevance: A variety of DBT interventions with therapists trained in the DBT suicide risk assessment and management protocol are effective for reducing suicide attempts and NSSI episodes. Interventions that include DBT skills training are more effective than DBT without skills training, and standard DBT may be superior in some areas. Trial registration: clinicaltrials.gov Identifier: NCT00183651.

JAMA psychiatry · randomised controlled trial · 325 citationsread the source →

Comparison of behavioural activation with guided self-help for treatment of depression in adults with intellectual disabilities: a randomised controlled trial.

Background: Psychological therapies are first-line interventions for depression, but existing provision is not accessible for many adults with intellectual disabilities. We investigated the clinical and cost-effectiveness of a behavioural activation intervention (BeatIt) for people with intellectual disabilities and depression. BeatIt was compared with a guided self-help intervention (StepUp). Methods: We did a multicentre, single-blind, randomised, controlled trial with follow-up at 4 months and 12 months after randomisation. Participants aged 18 years or older, with mild to moderate intellectual disabilities and clinically significant depression were recruited from health and social care services in the UK. The primary outcome was the Glasgow Depression Scale for people with a Learning Disability (GDS-LD) score at 12 months. Analyses were done on an intention-to-treat basis. This trial is registered with ISCRTN, number ISRCTN09753005. Findings: Between Aug 8, 2013, and Sept 1, 2015, 161 participants were randomly assigned (84 to BeatIt; 77 to StepUp); 141 (88%) participants completed the trial. No group differences were found in the effects of BeatIt and StepUp based on GDS-LD scores at 12 months (12·03 [SD 7·99] GDS-LD points for BeatIt vs 12·43 [SD 7·64] GDS-LD points for StepUp; mean difference 0·26 GDS-LD points [95% CI -2·18 to 2·70]; p=0·833). Within-group improvements in GDS-LD scores occurred in both groups at 12 months (BeatIt, mean change -4·2 GDS-LD points [95% CI -6·0 to -2·4], p<0·0001; StepUp, mean change -4·5 GDS-LD points [-6·2 to -2·7], p<0·0001), with large effect sizes (BeatIt, 0·590 [95% CI 0·337-0·844]; StepUp, 0·627 [0·380-0·873]). BeatIt was not cost-effective when compared with StepUp, although the economic analyses indicated substantial uncertainty. Treatment costs were only approximately 3·6-6·8% of participants' total support costs. No treatment-related or trial-related adverse events were reported. Interpretation: This study is, to our knowledge, the first large randomised controlled trial assessing individual psychological interventions for people with intellectual disabilities and mental health problems. These findings show that there is no evidence that BeatIt is more effective than StepUp; both are active and potentially effective interventions. Funding: National Institute for Health Research.

The lancet. Psychiatry · randomised controlled trial · 49 citationsread the source →

Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study.

Background: Bivalent oral poliovirus vaccine (bOPV; types 1 and 3) is expected to replace trivalent OPV (tOPV) globally by April, 2016, preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus. Because data are needed on sequential IPV-bOPV schedules, we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants. Methods: We did a randomised, controlled, open-label, non-inferiority trial with healthy, full-term (>2·5 kg birthweight) infants aged 8 weeks (± 7 days) at six well-child clinics in Santiago, Chile. We used supplied lists to randomly assign infants (1:1:1) to receive three polio vaccinations (IPV by injection or bOPV as oral drops) at age 8, 16, and 24 weeks in one of three sequential schedules: IPV-bOPV-bOPV, IPV-IPV-bOPV, or IPV-IPV-IPV. We did the randomisation with blocks of 12 stratified by study site. All analyses were done in a masked manner. Co-primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion (within a 10% margin) and antibody titres (within two-thirds log2 titres) to poliovirus serotypes 1 and 3 at age 28 weeks, analysed in the per-protocol population. Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks. Safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01841671, and is closed to new participants. Findings: Between April 25 and August 1, 2013, we assigned 570 infants to treatment: 190 to IPV-bOPV-bOPV, 192 to IPV-IPV-bOPV, and 188 to IPV-IPV-IPV. 564 (99%) were vaccinated and included in the intention-to-treat cohort, and 537 (94%) in the per-protocol analyses. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroconversion to type 1 poliovirus were 166 (98·8%) of 168, 95% CI 95·8-99·7; 178 (100%), 97·9-100·0; and 175 (100%), 97·9-100·0. Proportions with seroconvsion to type 3 poliovirus were 163 (98·2%) of 166, 94·8-99·4; 177 (100%), 97·9-100·0, and 172 (98·9%) of 174, 95·9-99·7. Non-inferiority was thus shown for the bOPV-containing schedules compared with the all-IPV schedule, with no significant differences between groups. In the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, the proportions of children with seroprotective antibody titres to type 1 poliovirus were 168 (98·8%) of 170, 95% CI 95·8-99·7; 181 (100%), 97·9-100·0; and 177 (100%), 97·9-100·0. Proportions to type 3 poliovirus were 166 (98·2%) of 169, 94·9-99·4; 180 (100%), 97·9-100·0; and 174 (98·9%) of 176, 96·0-99·7. Non-inferiority comparisons could not be done for this outcome because median titres for the groups receiving OPV were greater than the assay's upper limit of detection (log2 titres >10·5). The proportions of children seroconverting to type 2 poliovirus in the IPV-bOPV-bOPV, IPV-IPV-bOPV, and IPV-IPV-IPV groups, respectively, were 130 (77·4%) of 168, 95% CI 70·5-83·0; 169 (96·0%) of 176, 92·0-98·0; and 175 (100%), 97·8-100. IPV-bOPV schedules resulted in almost a 0·3 log reduction of type 2 faecal shedding compared with the IPV-only schedule. No participants died during the trial; 81 serious adverse events were reported, of which one was thought to be possibly vaccine-related (intestinal intussusception). Interpretation: Seroconversion rates against polioviruses types 1 and 3 were non-inferior in sequential schedules containing IPV and bOPV, compared with an all-IPV schedule, and proportions of infants with protective antibodies were high after all three schedules. One or two doses of bOPV after IPV boosted intestinal immunity for poliovirus type 2, suggesting possible cross protection. Additionally, there was evidence of humoral priming for type 2 from one dose of IPV. Our findings could give policy makers flexibility when choosing a vaccination schedule, especially when trying to eliminate vaccine-associated and vaccine-derived poliomyelitis. Funding: Bill & Melinda Gates Foundation.

The Lancet. Infectious diseases · randomised controlled trial · 60 citationsread the source →

Sustained effectiveness and cost-effectiveness of Counselling for Alcohol Problems, a brief psychological treatment for harmful drinking in men, delivered by lay counsellors in primary care: 12-month follow-up of a randomised controlled trial.

Background: Counselling for Alcohol Problems (CAP), a brief intervention delivered by lay counsellors, enhanced remission and abstinence over 3 months among male primary care attendees with harmful drinking in a setting in India. We evaluated the sustainability of the effects after treatment termination, the cost-effectiveness of CAP over 12 months, and the effects of the hypothesized mediator 'readiness to change' on clinical outcomes. Methods and findings: Male primary care attendees aged 18-65 years screening with harmful drinking on the Alcohol Use Disorders Identification Test (AUDIT) were randomised to either CAP plus enhanced usual care (EUC) (n = 188) or EUC alone (n = 189), of whom 89% completed assessments at 3 months, and 84% at 12 months. Primary outcomes were remission and mean standard ethanol consumed in the past 14 days, and the proposed mediating variable was readiness to change at 3 months. CAP participants maintained the gains they showed at the end of treatment through the 12-month follow-up, with the proportion with remission (AUDIT score < 8: 54.3% versus 31.9%; adjusted prevalence ratio [aPR] 1.71 [95% CI 1.32, 2.22]; p < 0.001) and abstinence in the past 14 days (45.1% versus 26.4%; adjusted odds ratio 1.92 [95% CI 1.19, 3.10]; p = 0.008) being significantly higher in the CAP plus EUC arm than in the EUC alone arm. CAP participants also fared better on secondary outcomes including recovery (AUDIT score < 8 at 3 and 12 months: 27.4% versus 15.1%; aPR 1.90 [95% CI 1.21, 3.00]; p = 0.006) and percent of days abstinent (mean percent [SD] 71.0% [38.2] versus 55.0% [39.8]; adjusted mean difference 16.1 [95% CI 7.1, 25.0]; p = 0.001). The intervention effect for remission was higher at 12 months than at 3 months (aPR 1.50 [95% CI 1.09, 2.07]). There was no evidence of an intervention effect on Patient Health Questionnaire 9 score, suicidal behaviour, percentage of days of heavy drinking, Short Inventory of Problems score, WHO Disability Assessment Schedule 2.0 score, days unable to work, or perpetration of intimate partner violence. Economic analyses indicated that CAP plus EUC was dominant over EUC alone, with lower costs and better outcomes; uncertainty analysis showed a 99% chance of CAP being cost-effective per remission achieved from a health system perspective, using a willingness to pay threshold equivalent to 1 month's wages for an unskilled manual worker in Goa. Readiness to change level at 3 months mediated the effect of CAP on mean standard ethanol consumption at 12 months (indirect effect -6.014 [95% CI -13.99, -0.046]). Serious adverse events were infrequent, and prevalence was similar by arm. The methodological limitations of this trial are the susceptibility of self-reported drinking to social desirability bias, the modest participation rates of eligible patients, and the examination of mediation effects of only 1 mediator and in only half of our sample. Conclusions: CAP's superiority over EUC at the end of treatment was largely stable over time and was mediated by readiness to change. CAP provides better outcomes at lower costs from a societal perspective. Trial registration: ISRCTN registry ISRCTN76465238.

PLoS medicine · randomised controlled trial · 56 citationsread the source →

Effects of ParentCorps in Prekindergarten on Child Mental Health and Academic Performance: Follow-up of a Randomized Clinical Trial Through 8 Years of Age.

Importance: Low-income minority children living in urban neighborhoods are at high risk for mental health problems and underachievement. ParentCorps, a family-centered, school-based intervention in prekindergarten, improves parenting and school readiness (ie, self-regulation and preacademic skills) in 2 randomized clinical trials. The longer-term effect on child mental health and academic performance is not known. Objective: To examine whether ParentCorps delivered as an enhancement to prekindergarten programs in high-poverty urban schools leads to fewer mental health problems and increased academic performance in the early elementary school years. Design, setting, and participants: This is a 3-year follow-up study of a cluster randomized clinical trial of ParentCorps in public schools with prekindergarten programs in New York City. Ten elementary schools serving a primarily low-income, black student population were randomized in 2005, and 4 consecutive cohorts of prekindergarten students were enrolled from September 12, 2005, through December 31, 2008. We report follow-up for the 3 cohorts enrolled after the initial year of implementation. Data analysis was performed from September 1, 2014, to December 31, 2015. Interventions: ParentCorps included professional development for prekindergarten and kindergarten teachers and a program for parents and prekindergarten students (13 two-hour group sessions delivered after school by teachers and mental health professionals). Main outcomes and measures: Annual teacher ratings of mental health problems and academic performance and standardized tests of academic achievement in kindergarten and second grade by testers masked to the intervention or control group randomization. Results: A total of 1050 children (4 years old; 518 boys [49.3%] and 532 girls [50.7%]) in 99 prekindergarten classrooms participated in the trial (88.1% of the prekindergarten population), with 792 students enrolled from 2006 to 2008. Most families in the follow-up study (421 [69.6%]) were low income; 680 (85.9%) identified as non-Latino black, 78 (9.8%) as Latino, and 34 (4.3%) as other. Relative to their peers in prekindergarten programs, children in ParentCorps-enhanced prekindergarten programs had lower levels of mental health problems (Cohen d = 0.44; 95% CI, 0.08-0.81) and higher teacher-rated academic performance (Cohen d = 0.21; 95% CI, 0.02-0.39) in second grade. Conclusions and relevance: Intervention in prekindergarten led to better mental health and academic performance 3 years later. Family-centered early intervention has the potential to prevent problems and reduce disparities for low-income minority children. Trial registration: clinicaltrials.gov Identifier: NCT01670227.

JAMA pediatrics · randomised controlled trial · 52 citationsread the source →

Promoting school climate and health outcomes with the SEHER multi-component secondary school intervention in Bihar, India: a cluster-randomised controlled trial.

Background: School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing. Methods: We did a cluster-randomised trial to assess the effectiveness of a multi-component whole-school health promotion intervention (SEHER) with integrated economic and process evaluations in grade 9 students (aged 13-14 years) at government-run secondary schools in the Nalanda district of Bihar state, India. Schools were randomly assigned (1:1:1) to three groups: the SEHER intervention delivered by a lay counsellor (the SEHER Mitra [SM] group), the SEHER intervention delivered by a teacher (teacher as SEHER Mitra [TSM] group), and a control group in which only the standard government-run classroom-based life-skills Adolescence Education Program was implemented. The primary outcome was school climate measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Students were assessed at the start of the academic year (June, 2015) and again 8 months later at the end of the academic year (March, 2016) via self-completed questionnaires. This study is registered with ClinicalTrials.gov, number NCT02484014. Findings: Of the 112 eligible schools in the Nalanda district, 75 were randomly selected to participate in the trial. We randomly assigned 25 schools to each of the three groups. One school subsequently dropped out of the TSM group, leaving 24 schools in this group. The baseline survey included a total of 13 035 participants, and the endpoint survey included 14 414 participants. Participants in the SM-delivered intervention schools had substantially higher school climate scores at endpoint survey than those in the control group (BBSCQ baseline-adjusted mean difference [aMD] 7·57 [95% CI 6·11-9·03]; effect size 1·88 [95% CI 1·44-2·32], p<0·0001) and the TSM-delivered intervention (aMD 7·57 [95% CI 6·06-9·08]; effect size 1·88 [95% CI 1·43-2·34], p<0·0001). There was no effect of the TSM-delivered intervention compared with control (aMD -0·009 [95% CI -1·53 to 1·51], effect size 0·00 [95% CI -0·45 to 0·44], p=0·99). Compared with the control group, participants in the SM-delivered intervention schools had moderate to large improvements in the secondary outcomes of depression (aMD -1·23 [95% CI -1·89 to -0·57]), bullying (aMD -0·91 [95% CI -1·15 to -0·66]), violence victimisation (odds ratio [OR] 0·62 [95% CI 0·46-0·84]), violence perpetration (OR 0·68 [95% CI 0·48-0·96]), attitude towards gender equity (aMD 0·41 [95% CI 0·21-0·61]), and knowledge of reproductive and sexual health (aMD 0·29 [95% CI 0·06-0·53]). Similar results for these secondary outcomes were noted for the comparison between SM-delivered intervention schools and TSM-delivered intervention schools (depression: aMD -1·23 [95% CI -1·91 to -0·55]; bullying: aMD -0·83 [95% CI -1·08 to -0·57]; violence victimisation: OR 0·49 [95% CI 0·35-0·67]; violence perpetration: OR 0·49 [95% CI 0·34-0·71]; attitude towards gender equity: aMD 0·23 [95% CI 0·02-0·44]; and knowledge of reproductive and sexual health: aMD 0·22 [95% CI -0·02 to 0·47]). However, no effects on these secondary outcomes were observed for the TSM-delivered intervention schools compared with the control group (depression: aMD -0·03 [95% CI -0·70 to 0·65]; bullying: aMD -0·08 [95% CI -0·34 to 0·18]; violence victimisation: OR 1·27 [95% CI 0·93-1·73]; violence perpetration: OR 1·37 [95% CI 0·95-1·95]; attitude towards gender equity: aMD 0·17 [95% CI -0·09 to 0·38]; and knowledge of reproductive and sexual health: aMD 0·06 [95% CI -0·18 to 0·32]). Interpretation: The multi-component whole-school SEHER health promotion intervention had substantial beneficial effects on school climate and health-related outcomes when delivered by lay counsellors, but no effects when delivered by teachers. Future research should focus on the evaluation of the scaling up of the SEHER intervention in diverse contexts and delivery agents. Funding: John D. and Catherine T. MacArthur Foundation, USA and the United Nations Population Fund India Office.

Lancet (London, England) · randomised controlled trial · 121 citationsread the source →

Effect of an Internet-Delivered Stepped-Care Program vs In-Person Cognitive Behavioral Therapy on Obsessive-Compulsive Disorder Symptoms in Children and Adolescents: A Randomized Clinical Trial.

Importance: In most countries, young people with obsessive-compulsive disorder have limited access to specialist cognitive behavioral therapy (CBT), a first-line treatment. Objective: To investigate whether internet-delivered CBT implemented in a stepped-care model is noninferior to in-person CBT for pediatric obsessive-compulsive disorder. Design, setting and participants: A randomized clinical noninferiority trial conducted at 2 specialist child and adolescent mental health clinics in Sweden. Participants included 152 individuals aged 8 to 17 years with obsessive-compulsive disorder. Enrollment began in October 2017 and ended in May 2019. Follow-up ended in April 2020. Interventions: Participants randomized to the stepped-care group (n = 74) received internet-delivered CBT for 16 weeks. Nonresponders at the 3-month follow-up were then offered a course of traditional face-to-face treatment. Participants randomized to the control group (n = 78) immediately received in-person CBT for 16 weeks. Nonresponders at the 3-month follow-up received additional face-to-face treatment. Main outcomes and measures: The primary outcome was the masked assessor-rated Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score at the 6-month follow-up. The scale includes 10 items rated from 0 (no symptoms) to 4 (extreme symptoms), yielding a total score range of 0 to 40, with higher scores indicating greater severity. Assessors were masked to treatment allocation at pretreatment, posttreatment, 3-month follow-up, and 6-month follow-up assessments. The predefined noninferiority margin was 4 points on the CY-BOCS. Results: Among the 152 randomized participants (mean age, 13.4 years; 94 [62%] females), 151 (99%) completed the trial. At the 3-month follow-up, 34 participants (46%) in the stepped-care group and 23 (30%) in the in-person CBT group were nonresponders. At the 6-month follow-up, the CY-BOCS score was 11.57 points in the stepped-care group vs 10.57 points in the face-to-face treatment group, corresponding to an estimated mean difference of 0.91 points ([1-sided 97.5% CI, -∞ to 3.28]; P for noninferiority = .02). Increased anxiety (30%-36%) and depressive symptoms (20%-28%) were the most frequently reported adverse events in both groups. There were 2 unrelated serious adverse events (1 in each group). Conclusions and relevance: Among children and adolescents with obsessive-compulsive disorder, treatment with an internet-delivered CBT program followed by in-person CBT if necessary compared with in-person CBT alone resulted in a noninferior difference in symptoms at the 6-month follow-up. Further research is needed to understand the durability and generalizability of these findings. Trial registration: ClinicalTrials.gov Identifier: NCT03263546.

JAMA · randomised controlled trial · 42 citationsread the source →

Effects of controlled school-based multi-component model of nutrition and lifestyle interventions on behavior modification, anthropometry and metabolic risk profile of urban Asian Indian adolescents in North India.

Background/objectives: To study the effectiveness of a multi-component intervention model of nutrition and lifestyle education on behavior modification, anthropometry and metabolic risk profile of urban Asian-Indian adolescents in North India. Subjects/methods: Two schools matched for student strength and middle socioeconomic strata were randomly allocated to intervention and control group. Changes in nutrition-related knowledge, attitude, lifestyle practices, food frequency and body image of eleventh-grade students (15-17 years) in both schools were tested using a validated questionnaire. Anthropometric and biochemical measurements were made using standard methods. Segmental body composition analysis was carried out using an 8-electrode multifrequency bioelectrical impedance method of body fat estimation. Results: At 6 months follow-up, significant improvement in several domains of knowledge was observed in intervention children (n=99; males=60; females=39) as compared with control school children (n=102; males=61; females=41). In the intervention group, significantly lower proportion of children consumed aerated drinks (15.1%; P<0.001) and energy-dense unhealthy foods (8.9%; P=0.03), whereas significantly higher proportion brought tiffin (packed lunch) to school (14.9%; P=0.004) and brought a fruit in their tiffin (30.7%; P<0.001) as compared with the control group. Significant decrease in mean waist circumference (P=0.02, 95% confidence interval (CI)=-2.43,-0.17), sagittal abdominal diameter (P<0.001, 95% CI=-0.82,-0.09), waist-to-hip ratio (P=0.02, 95% CI=-0.03,-0.004) and fasting blood glucose (P=0.05, 95% CI=-0.09, 5.00) was seen in intervention as compared with control school children. Conclusions: Multi-component model of nutrition and lifestyle education was successful in improving the nutrition-related knowledge, eating habits and lifestyle practices, and resulted in beneficial changes in anthropometric and biochemical profiles of the Asian Indian adolescents. This model should be applied on countrywide basis to prevent obesity and diabetes.

European journal of clinical nutrition · randomised controlled trial · 114 citationsread the source →

Stress management interventions in the workplace improve stress reactivity: a randomised controlled trial.

Objective: To examine the long-term effects of a stress management intervention (SMI) based on the effort-reward imbalance (ERI) model, on psychological and biological reactions to work stress. Methods: 174 lower or middle management employees (99% male) were randomly assigned to an intervention or a waiting control group. The programme comprised 24 × 45 min group sessions (2 full days followed by two 4 × 45 min sessions within the next 8 months) on individual work stress situations. The primary endpoint was perceived stress reactivity (Stress Reactivity Scale, SRS), while secondary endpoints were salivary cortisol and α-amylase, anxiety and depression, and ERI. Assessments were repeated in 154 participants 1 year later. Results: SRS score decreased in both groups. A two-factor ANOVA with repeated measures showed a significant time × group effect (F=5.932; p=0.016) with the greater reduction in the intervention group. For SRS, the effect size (Cohen's d) after 1 year was d=0.416 in the intervention and d=0.166 in the control group. α-Amylase as a measure of sympathetic nervous system activation, decreased more strongly in the intervention group (area under the daytime curve and daytime slope: time × group effect p=0.076 and p=0.075). No difference was observed for cortisol. For depression, anxiety and ERI, improvements were higher in the intervention group but did not reach statistical significance. Conclusions: SMI based on work stress theory, is effective in reducing perceived stress reactivity and sympathetic activation in lower and middle management employees. Other mental health parameters and ERI show a tendency towards improvement. These beneficial effects are present 1 year later.

Occupational and environmental medicine · randomised controlled trial · 66 citationsread the source →

Internet-based intervention for smoking cessation (StopAdvisor) in people with low and high socioeconomic status: a randomised controlled trial.

Background: Internet-based interventions for smoking cessation could help millions of people stop smoking at very low unit costs; however, long-term biochemically verified evidence is scarce and such interventions might be less effective for smokers with low socioeconomic status than for those with high status because of lower online literacy to engage with websites. We aimed to assess a new interactive internet-based intervention (StopAdvisor) for smoking cessation that was designed with particular attention directed to people with low socioeconomic status. Methods: We did this online randomised controlled trial between Dec 6, 2011, and Oct 11, 2013, in the UK. Participants aged 18 years and older who smoked every day were randomly assigned (1:1) to receive treatment with StopAdvisor or an information-only website. Randomisation was automated with an unseen random number function embedded in the website to establish which treatment was revealed after the online baseline assessment. Recruitment continued until the required sample size had been achieved from both high and low socioeconomic status subpopulations. Participants, and researchers who obtained data and did laboratory analyses, were masked to treatment allocation. The primary outcome was 6 month sustained, biochemically verified abstinence. The main secondary outcome was 6 month, 7 day biochemically verified point prevalence. Analysis was by intention to treat. Homogeneity of intervention effect across the socioeconomic subsamples was first assessed to establish whether overall or separate subsample analyses were appropriate. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN99820519. Findings: We randomly assigned 4613 participants to the StopAdvisor group (n=2321) or the control group (n=2292); 2142 participants were of low socioeconomic status and 2471 participants were of high status. The overall rate of smoking cessation was similar between participants in the StopAdvisor and control groups for the primary (237 [10%] vs 220 [10%] participants; relative risk [RR] 1·06, 95% CI 0·89-1·27; p=0·49) and the secondary (358 [15%] vs 332 [15%] participants; 1·06, 0·93-1·22; p=0·37) outcomes; however, the intervention effect differed across socioeconomic status subsamples (1·44, 0·99-2·09; p=0·0562 and 1·37, 1·02-1·84; p=0·0360, respectively). StopAdvisor helped participants with low socioeconomic status stop smoking compared with the information-only website (primary outcome: 90 [8%] of 1088 vs 64 [6%] of 1054 participants; RR 1·36, 95% CI 1·00-1·86; p=0·0499; secondary outcome: 136 [13%] vs 100 [10%] participants; 1·32, 1·03-1·68, p=0·0267), but did not improve cessation rates in those with high socioeconomic status (147 [12%] of 1233 vs 156 [13%] of 1238 participants; 0·95, 0·77-1·17; p=0·61 and 222 [18%] vs 232 [19%] participants; 0·96, 0·81-1·13, p=0·64, respectively). Interpretation: StopAdvisor was more effective than an information-only website in smokers of low, but not high, socioeconomic status. StopAdvisor could be implemented easily and made freely available, which would probably improve the success rates of smokers with low socioeconomic status who are seeking online support. Funding: National Prevention Research Initiative.

The Lancet. Respiratory medicine · randomised controlled trial · 99 citationsread the source →

Mindfulness-based cognitive therapy for preventing relapse in recurrent depression: a randomized dismantling trial.

Objective: We compared mindfulness-based cognitive therapy (MBCT) with both cognitive psychological education (CPE) and treatment as usual (TAU) in preventing relapse to major depressive disorder (MDD) in people currently in remission following at least 3 previous episodes. Method: A randomized controlled trial in which 274 participants were allocated in the ratio 2:2:1 to MBCT plus TAU, CPE plus TAU, and TAU alone, and data were analyzed for the 255 (93%; MBCT = 99, CPE = 103, TAU = 53) retained to follow-up. MBCT was delivered in accordance with its published manual, modified to address suicidal cognitions; CPE was modeled on MBCT, but without training in meditation. Both treatments were delivered through 8 weekly classes. Results: Allocated treatment had no significant effect on risk of relapse to MDD over 12 months follow-up, hazard ratio for MBCT vs. CPE = 0.88, 95% CI [0.58, 1.35]; for MBCT vs. TAU = 0.69, 95% CI [0.42, 1.12]. However, severity of childhood trauma affected relapse, hazard ratio for increase of 1 standard deviation = 1.26 (95% CI [1.05, 1.50]), and significantly interacted with allocated treatment. Among participants above median severity, the hazard ratio was 0.61, 95% CI [0.34, 1.09], for MBCT vs. CPE, and 0.43, 95% CI [0.22, 0.87], for MBCT vs. TAU. For those below median severity, there were no such differences between treatment groups. Conclusion: MBCT provided significant protection against relapse for participants with increased vulnerability due to history of childhood trauma, but showed no significant advantage in comparison to an active control treatment and usual care over the whole group of patients with recurrent depression.

Journal of consulting and clinical psychology · randomised controlled trial · 215 citationsread the source →

Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial.

Background: Obesity is associated with a reduction in life expectancy and an increase in mortality from cardiovascular diseases, cancer, and other causes. We therefore assessed the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss and metabolic risk reduction in individuals who were overweight and obese, with two or more risk factors. Methods: In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged 18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities (hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo, once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0 mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered orally. Patients were randomly assigned by use of a computer-generated algorithm that was implemented through an interactive voice response system, and were stratified by sex and diabetic status. Investigators, patients, and study sponsors were masked to treatment. Primary endpoints were the percentage change in bodyweight and the proportion of patients achieving at least 5% weight loss. Analysis was by intention to treat. This study is registered with Clinical Trials.gov, number NCT00553787. Findings: Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate 46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981 patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4 kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1; p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine 7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine 15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were 72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001). The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and 204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively), insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%], 99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively). 38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate 46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related adverse events. Interpretation: The combination of phentermine and topiramate, with office-based lifestyle interventions, might be a valuable treatment for obesity that can be provided by family doctors. Funding: Vivus.

Lancet (London, England) · randomised controlled trial · 667 citationsread the source →

Anxiety diagnoses in smokers seeking cessation treatment: relations with tobacco dependence, withdrawal, outcome and response to treatment.

Aims: To understand the relations among anxiety disorders and tobacco dependence, withdrawal symptoms, response to smoking cessation pharmacotherapy and ability to quit smoking. Design: Randomized placebo-controlled clinical trial. Participants received six 10-minute individual counseling sessions and either: placebo, bupropion SR, nicotine patch, nicotine lozenge, bupropion SR + nicotine lozenge or nicotine patch + nicotine lozenge. Setting: Two urban research sites. Participants: Data were collected from 1504 daily smokers (>9 cigarettes per day) who were motivated to quit smoking and did not report current diagnoses of schizophrenia or psychosis or bupropion use. Measurements: Participants completed baseline assessments, the Composite International Diagnostic Interview and ecological momentary assessments for 2 weeks. Findings: A structured clinical interview identified participants who ever met criteria for a panic attack (n = 455), social anxiety (n = 199) or generalized anxiety disorder (n = 99), and those who qualified for no anxiety diagnosis (n = 891). Smokers with anxiety disorders reported higher levels of nicotine dependence and pre-quit withdrawal symptoms. Those ever meeting criteria for panic attacks or social anxiety disorder showed greater quit-day negative affect. Smokers ever meeting criteria for anxiety disorders were less likely to be abstinent at 8 weeks and 6 months post-quit and showed no benefit from single-agent or combination-agent pharmacotherapies. Conclusions: Anxiety diagnoses were common among treatment-seeking smokers and were related to increased motivation to smoke, elevated withdrawal, lack of response to pharmacotherapy and impaired ability to quit smoking. These findings could guide treatment assignment algorithms and treatment development for smokers with anxiety diagnoses.

Addiction (Abingdon, England) · randomised controlled trial · 141 citationsread the source →

Cognitive Reactivity to Sad Mood Provocation and the Prediction of Depressive Relapse

CONTEXT: Episode remission in unipolar major depression, while distinguished by minimal symptom burden, can also be a period of marked sensitivity to emotional stress as well as an increased risk of relapse. OBJECTIVE: To examine whether mood-linked changes in dysfunctional thinking predict relapse in recovered patients who were depressed. DESIGN: In phase 1 of this study, patients with major depressive disorder were randomly assigned to receive either antidepressant medication or cognitive behavior therapy. In phase 2, patients who achieved clinical remission underwent sad mood provocation and were then observed with regular clinical assessments for 18 months. SETTING: Outpatient psychiatric clinics at the Centre for Addiction and Mental Health, Toronto, Ontario. PARTICIPANTS: A total of 301 outpatients with major depressive disorder, aged 18 to 65 years, participated in phase 1 of this study and 99 outpatients with major depressive disorder in remission, aged 18 to 65 years, participated in phase 2. MAIN OUTCOME MEASURE: Occurrence of a relapse meeting DSM-IV criteria for a major depressive episode as assessed by the longitudinal interval follow-up evaluation and a Hamilton Depression Rating Scale score of 16 or greater. RESULTS: Patients who recovered through antidepressant medication showed greater cognitive reactivity following the mood provocation than those who received cognitive behavior therapy. Regardless of type of prior treatment, the magnitude of mood-linked cognitive reactivity was a significant predictor of relapse over the subsequent 18 months. Patients whose mood-linked endorsement of dysfunctional attitudes increased by a minimum of 8 points had a significantly shorter time to relapse than those whose scores were not as elevated. CONCLUSIONS: The vulnerability of remitted depressed patients for illness relapse may be related to the (re)activation of depressive thinking styles triggered by temporary dysphoric states. This is the first study to link such differences to prognosis following successful treatment for depression. Further understanding of factors predisposing to relapse/recurrence in recovered patients may help to shorten the potentially lifelong course of depression.

Archives of General Psychiatry · randomised controlled trial · 469 citationsread the source →

Cancer mortality in India: a nationally representative survey.

Background: The age-specific mortality rates and total deaths from specific cancers have not been documented for the various regions and subpopulations of India. We therefore assessed the cause of death in 2001-03 in homes in small areas that were chosen to be representative of all the parts of India. Methods: At least 130 trained physicians independently assigned causes to 122,429 deaths, which occurred in 1·1 million homes in 6671 small areas that were randomly selected to be representative of all of India, based on a structured non-medical surveyor's field report. Findings: 7137 of 122,429 study deaths were due to cancer, corresponding to 556,400 national cancer deaths in India in 2010. 395,400 (71%) cancer deaths occurred in people aged 30-69 years (200,100 men and 195,300 women). At 30-69 years, the three most common fatal cancers were oral (including lip and pharynx, 45,800 [22·9%]), stomach (25,200 [12·6%]), and lung (including trachea and larynx, 22,900 [11·4%]) in men, and cervical (33,400 [17·1%]), stomach (27,500 [14·1%]), and breast (19,900 [10·2%]) in women. Tobacco-related cancers represented 42·0% (84,000) of male and 18·3% (35,700) of female cancer deaths and there were twice as many deaths from oral cancers as lung cancers. Age-standardised cancer mortality rates per 100,000 were similar in rural (men 95·6 [99% CI 89·6-101·7] and women 96·6 [90·7-102·6]) and urban areas (men 102·4 [92·7-112·1] and women 91·2 [81·9-100·5]), but varied greatly between the states, and were two times higher in the least educated than in the most educated adults (men, illiterate 106·6 [97·4-115·7] vs most educated 45·7 [37·8-53·6]; women, illiterate 106·7 [99·9-113·6] vs most educated 43·4 [30·7-56·1]). Cervical cancer was far less common in Muslim than in Hindu women (study deaths 24, age-standardised mortality ratio 0·68 [0·64-0·71] vs 340, 1·06 [1·05-1·08]). Interpretation: Prevention of tobacco-related and cervical cancers and earlier detection of treatable cancers would reduce cancer deaths in India, particularly in the rural areas that are underserved by cancer services. The substantial variation in cancer rates in India suggests other risk factors or causative agents that remain to be discovered. Funding: Bill & Melinda Gates Foundation and US National Institutes of Health.

Lancet (London, England) · 296 citationsread the source →

International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

Background: In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses. Methods: The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. Findings: We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and -2·69 mm (3·2) for head circumference; 0·83 mm (0·9), -0·05 mm (0·8), and -0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and -1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and -4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and -0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. Interpretation: We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. Funding: Bill & Melinda Gates Foundation.

Lancet (London, England) · cohort or longitudinal · 589 citationsread the source →

Digital Technologies for Health Promotion and Disease Prevention in Older People: Scoping Review.

Background: Digital technologies have the potential to contribute to health promotion and disease prevention in the aging world. Objective: This study aims to identify digital technologies for health promotion and disease prevention that could be used independently by older people in nonclinical settings using a scoping review. Methods: Through database (MEDLINE, PsycINFO, CINAHL, and SCOPUS; to March 3, 2022) and manual searches (to June 14, 2022), 90 primary studies and 8 systematic reviews were included in this scoping review. The eligibility was based on the PCC (Population, Concept, and Context) criteria: (1) people aged 50 years or older (population), (2) any digital (health) technology (eg, smartphone apps, websites, virtual reality; concept), and (3) health promotion and disease prevention in daily life in nonclinical and noninstitutional settings (context). Data items included study characteristics, PCC criteria, opportunities versus challenges, and evidence gaps. Data were synthesized using descriptive statistics or narratively described by identifying common themes. Results: The studies were published in 2005-2022 and originated predominantly from North America and Europe. Most primary studies were nonrandomized, reported quantitative data, and investigated effectiveness or feasibility (eg, acceptance or usability) of digital technologies in older people. The participants were aged 50 years to 99 years, predominantly female, affluent (ie, with high income, education, and digital competence), and intended to use or used digital technologies for a median of 3 months independently at home or in community settings. The digital technologies included mobile or nonmobile technologies or virtual reality. The studies used "modern devices" (eg, smartphones, wearables, or gaming consoles) or modern and "older devices" (eg, computers or mobile phones). The users interacted with digital technologies via websites, emails, text messages, apps, or virtual reality. Health targets of digital technologies were mobility, mental health, nutrition, or cognition. The opportunities versus challenges of digital technologies were (1) potential health benefits versus unclear or no benefits for some outcomes, (2) monitoring of health versus ethical issues with data collection and management, (3) implications for functioning in daily life (ie, potential to prolong independent living) versus unclear application for clinical management or care, (4) tailoring of technical properties and content toward older users versus general use, (5) importance of human support for feasibility versus other factors required to improve feasibility, (6) reduction of social isolation versus access to digital technologies, and (7) improvement in digital competence versus digital divide. Conclusions: Various digital technologies were independently used by people aged 50 years or older for health promotion and disease prevention. Future studies should focus on (1) more diverse populations of older people, (2) new digital technologies, (3) other (clinical and care) settings, and (4) outcome evaluation to identify factors that could enhance any health benefits of digital technologies. International registered report identifier (irrid): RR2-10.2196/37729.

Journal of medical Internet research · review · 79 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

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How Do Corticosteroids Work in Asthma?

Reviews2 September 2003How Do Corticosteroids Work in Asthma?Peter J. Barnes, DM, DSc and Ian M. Adcock, PhDPeter J. Barnes, DM, DScFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this author and Ian M. Adcock, PhDFrom National Heart and Lung Institute, Imperial College, London, United Kingdom. Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-5_Part_1-200309020-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesAsthma is the most common chronic disease in westernized countries. Patients with asthma have an underlying chronic inflammation of the airways characterized by activated mast cells, eosinophils, and T-helper 2 lymphocytes. This results in increased responsiveness of the airways to such triggers as exercise, allergens, and air pollutants. This chronic inflammation underlies the typical symptoms of asthma, which include intermittent wheezing, coughing, shortness of breath, and chest tightness. Corticosteroids are the most effective treatment for asthma, and inhaled corticosteroids have become first-line treatment for children and adults with persistent symptoms. Corticosteroids suppress the chronic airway inflammation in patients with asthma, and the molecular ...References1. Busse WW, Lemanske RF. Asthma. N Engl J Med. 2001;344:350-62. [PMID: 11172168] CrossrefMedlineGoogle Scholar2. Barnes PJ, Chung KF, Page CP. Inflammatory mediators of asthma: an update. Pharmacol Rev. 1998;50:515-96. [PMID: 9860804] MedlineGoogle Scholar3. Barnes PJ, Adcock IM. Transcription factors and asthma. Eur Respir J. 1998;12:221-34. [PMID: 9701442] CrossrefMedlineGoogle Scholar4. Hart LA, Krishnan VL, Adcock IM, Barnes PJ, Chung KF. Activation and localization of transcription factor, nuclear factor-B, in asthma. 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Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol. 2000;20:6891-903. [PMID: 10958685] CrossrefMedlineGoogle Scholar10. Gao L, Cueto MA, Asselbergs F, Atadja P. Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem. 2002;277:25748-55. [PMID: 11948178] CrossrefMedlineGoogle Scholar11. Ito K, Caramori G, Lim S, Oates T, Chung KF, Barnes PJ, . Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med. 2002;166:392-6. [PMID: 12153977] CrossrefMedlineGoogle Scholar12. Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms [Editorial]. Clin Sci (Lond). 1998;94:557-72. [PMID: 9854452] CrossrefMedlineGoogle Scholar13. Barnes PJ. Molecular mechanisms of corticosteroids in allergic diseases. Allergy. 2001;56:928-36. [PMID: 11576070] CrossrefMedlineGoogle Scholar14. 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Molecular regulation of granulocyte macrophage colony-stimulating factor in human lung epithelial cells by interleukin (IL)-1, IL-4, and IL-13 involves both transcriptional and post-transcriptional mechanisms. Am J Respir Cell Mol Biol. 2000;22:582-9. [PMID: 10783130] CrossrefMedlineGoogle Scholar37. Caelles C, Gonzalez-Sancho JM, Munoz A. Nuclear hormone receptor antagonism with AP-1 by inhibition of the JNK pathway. Genes Dev. 1997;11:3351-64. [PMID: 9407028] CrossrefMedlineGoogle Scholar38. Vanden Berghe W, Vermeulen L, De Wilde G, De Bosscher K, Boone E, Haegeman G. Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6. Biochem Pharmacol. 2000;60:1185-95. [PMID: 11007957] CrossrefMedlineGoogle Scholar39. Lasa M, Brook M, Saklatvala J, Clark AR. Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38. Mol Cell Biol. 2001;21:771-80. [PMID: 11154265] CrossrefMedlineGoogle Scholar40. Lasa M, Abraham SM, Boucheron C, Saklatvala J, Clark AR. Dexamethasone causes sustained expression of mitogen-activated protein kinase (MAPK) phosphatase 1 and phosphatase-mediated inhibition of MAPK p38. Mol Cell Biol. 2002;22:7802-11. [PMID: 12391149] CrossrefMedlineGoogle Scholar41. Barnes PJ. Scientific rationale for inhaled combination therapy with long-acting 2-agonists and corticosteroids. Eur Respir J. 2002;19:182-91. [PMID: 11843317] CrossrefMedlineGoogle Scholar42. Adcock IM, Stevens DA, Barnes PJ. Interactions of glucocorticoids and 2-agonists. Eur Respir J. 1996;9:160-8. [PMID: 8834349] CrossrefMedlineGoogle Scholar43. Mak JC, Nishikawa M, Shirasaki H, Miyayasu K, Barnes PJ. Protective effects of a glucocorticoid on downregulation of pulmonary 2-adrenergic receptors in vivo. J Clin Invest. 1995;96:99-106. [PMID: 7615841] CrossrefMedlineGoogle Scholar44. Mak JC, Hisada T, Salmon M, Barnes PJ, Chung KF. Glucocorticoids reverse IL-1-induced impairment of -adrenoceptor-mediated relaxation and up-regulation of G-protein-coupled receptor kinases. Br J Pharmacol. 2002;135:987-96. [PMID: 11861327] CrossrefMedlineGoogle Scholar45. Eickelberg O, Roth M, Lorx R, Bruce V, Rudiger J, Johnson M, . Ligand-independent activation of the glucocorticoid receptor by 2-adrenergic receptor agonists in primary human lung fibroblasts and vascular smooth muscle cells. J Biol Chem. 1999;274:1005-10. [PMID: 9873044] CrossrefMedlineGoogle Scholar46. Pang L, Knox AJ. Regulation of TNF--induced eotaxin release from cultured human airway smooth muscle cells by 2-agonists and corticosteroids. FASEB J. 2001;15:261-269. [PMID: 11149914] CrossrefMedlineGoogle Scholar47. Korn SH, Wouters EF, Wesseling G, Arends JW, Thunnissen FB. Interaction between glucocorticoids and 2-agonists: and glucocorticoid-receptor mRNA expression in human bronchial epithelial cells. Biochem Pharmacol. 1998;56:1561-9. [PMID: 9973176] CrossrefMedlineGoogle Scholar48. Usmani OS, Maneechotesuwan K, Adcock IM, Barnes PJ. Glucocorticoid receptor activation following inhaled fluticasone and salmeterol [Abstract]. Am J Respir Crit Care Med. 2002;165:A616. Google Scholar49. Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med. 2003;167:813-8. [PMID: 12623857] CrossrefMedlineGoogle Scholar50. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, . A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci U S A. 2002;99:8921-6. [PMID: 12070353] CrossrefMedlineGoogle Scholar51. Evans DJ, Taylor DA, Zetterstrom O, Chung KF, O'Connor BJ, Barnes PJ. A comparison of low-dose inhaled budesonide plus theophylline and high-dose inhaled budesonide for moderate asthma. N Engl J Med. 1997;337:1412-8. [PMID: 9358138] CrossrefMedlineGoogle Scholar52. Ukena D, Harnest U, Sakalauskas R, Magyar P, Vetter N, Steffen H, . Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma. Eur Respir J. 1997;10:2754-60. [PMID: 9493656] CrossrefMedlineGoogle Scholar53. Lim S, Jatakanon A, Gordon D, Macdonald C, Chung KF, Barnes PJ. Comparison of high dose inhaled steroids, low dose inhaled steroids plus low dose theophylline, and low dose inhaled steroids alone in chronic asthma in general practice. Thorax. 2000;55:837-41. [PMID: 10992535] CrossrefMedlineGoogle Scholar54. Szefler SJ, Leung DY. Glucocorticoid-resistant asthma: pathogenesis and clinical implications for management. Eur Respir J. 1997;10:1640-7. [PMID: 9230260] CrossrefMedlineGoogle Scholar55. Barnes PJ. Steroid-resistant asthma. Eur Resp Rev. 2000;10:74-8. Google Scholar56. Spahn JD, Szefler SJ, Surs W, Doherty DE, Nimmagadda SR, Leung DY. A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity. J Immunol. 1996;157:2654-9. [PMID: 8805670] MedlineGoogle Scholar57. Irusen E, Matthews JG, Takahashi A, Barnes PJ, Chung KF, Adcock IM. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity: role in steroid-insensitive asthma. J Allergy Clin Immunol. 2002;109:649-57. [PMID: 11941315] CrossrefMedlineGoogle Scholar58. Hamid QA, Wenzel SE, Hauk PJ, Tsicopoulos A, Wallaert B, Lafitte JJ, . Increased glucocorticoid receptor in airway cells of glucocorticoid-insensitive asthma. Am J Respir Crit Care Med. 1999;159:1600-4. [PMID: 10228133] CrossrefMedlineGoogle Scholar59. Gagliardo R, Chanez P, Vignola AM, Bousquet J, Vachier I, Godard P, . Glucocorticoid receptor and in glucocorticoid dependent asthma. Am J Respir Crit Care Med. 2000;162:7-13. [PMID: 10903212] CrossrefMedlineGoogle Scholar60. Corrigan CJ, Brown PH, Barnes NC, Szefler SJ, Tsai JJ, Frew AJ, . Glucocorticoid resistance in chronic asthma. Glucocorticoid pharmacokinetics, glucocorticoid receptor characteristics, and inhibition of peripheral blood T cell proliferation by glucocorticoids in vitro. Am Rev Respir Dis. 1991;144:1016-25. [PMID: 1952426] CrossrefMedlineGoogle Scholar61. Adcock IM, Lane SJ, Brown CR, Lee TH, Barnes PJ. Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma. J Exp Med. 1995;182:1951-8. [PMID: 7500041] CrossrefMedlineGoogle Scholar62. Matthews JG, Ito K, Barnes PJ, Adcock IM. Corticosteroid-resistant and corticosteroid-dependent asthma: two clinical phenotypes can be associated with the same in vitro defects in nuclear translocation and acetylation of histone 4 [Abstract]. Am J Respir Crit Care Med. 2000;161:A189. Google Scholar63. Keatings VM, Jatakanon A, Worsdell YM, Barnes PJ. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997;155:542-8. [PMID: 9032192] CrossrefMedlineGoogle Scholar64. Culpitt SV, Maziak W, Loukidis S, Nightingale JA, Matthews JL, Barnes PJ. Effect of high dose inhaled steroid on cells, cytokines, and proteases in induced sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;160:1635-9. [PMID: 10556133] CrossrefMedlineGoogle Scholar65. Nightingale JA, Rogers DF, Fan Chung K, Barnes PJ. No effect of inhaled budesonide on the response to inhaled ozone in normal subjects. Am J Respir Crit Care Med. 2000;161:479-86. [PMID: 10673189] CrossrefMedlineGoogle Scholar66. Culpitt SV, Rogers DF, Shah P, De Matos C, Russell RE, Donnelly LE, . Impaired inhibition by dexamethasone of cytokine release by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;167:24-31. [PMID: 12406856] CrossrefMedlineGoogle Scholar67. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J. 2001;15:1110-2. [PMID: 11292684] CrossrefMedlineGoogle Scholar68. Ito K, Watanabe S, Kharitonov S, Hanazawa T, Adcock IM, Barnes PJ. Histone deacetylase activity and gene expression in COPD patients [Abstract]. Eur Respir J. 2001;18:316S. MedlineGoogle Scholar69. Montuschi P, Collins JV, Ciabattoni G, Lazzeri N, Corradi M, Kharitonov SA, . Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000;162:1175-7. [PMID: 10988150] CrossrefMedlineGoogle Scholar70. Barnes PJ, Pedersen S, Busse WW. Efficacy and safety of inhaled corticosteroids. New developments. Am J Respir Crit Care Med. 1998;157:S1-53. [PMID: 9520807] CrossrefMedlineGoogle Scholar71. Heck S, Kullmann M, Gast A, Ponta H, Rahmsdorf HJ, Herrlich P, . A distinct modulating domain in glucocorticoid receptor monomers in the repression of activity of the transcription factor AP-1. EMBO J. 1994;13:4087-95. [PMID: 8076604] CrossrefMedlineGoogle Scholar72. Adcock IM, Nasuhara Y, Stevens DA, Barnes PJ. Ligand-induced differentiation of glucocorticoid receptor (GR) trans-repression and transactivation: preferential targetting of NF-B and lack of I-B involvement. Br J Pharmacol. 1999;127:1003-11. [PMID: 10433509] CrossrefMedlineGoogle Scholar73. Vayssiere BM, Dupont S, Choquart A, Petit F, Garcia T, Marchandeau C, . Synthetic glucocorticoids that dissociate transactivation and AP-1 transrepression exhibit antiinflammatory activity in vivo. Mol Endocrinol. 1997;11:1245-55. [PMID: 9259316] CrossrefMedlineGoogle Scholar74. Belvisi MG, Wicks SL, Battram CH, Bottoms SE, Redford JE, Woodman P, . Therapeutic benefit of a dissociated glucocorticoid and the relevance of in vitro separation of transrepression from transactivation activity. J Immunol. 2001;166:1975-82. [PMID: 11160246] CrossrefMedlineGoogle Scholar75. Bledsoe RK, Montana VG, Stanley TB, Delves CJ, Apolito CJ, McKee DD, . Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell. 2002;110:93-105. [PMID: 12151000] CrossrefMedlineGoogle Scholar76. Barnes PJ. New treatments for COPD. Nat Rev Drug Discov. 2002;1:437-46. [PMID: 12119745] CrossrefMedlineGoogle Scholar77. Ito K, Lim S, Chung KF, Barnes PJ, Adcock IM. Theophylline enhances histone deacetylase activity and restores glucocorticoid function during oxidative stress [Abstract]. Am J Respir Crit Care Med. 2002;165:A625. Google Scholar Author, Article, and Disclosure InformationAffiliations: From National Heart and Lung Institute, Imperial College, London, United Kingdom. Disclosures:Grants received: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca); Grants pending: P.J. Barnes, I.M. Adcock (GlaxoSmithKline and AstraZeneca).Corresponding Author: P.J. Barnes, DM, DSc, Department of Thoracic Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom; e-mail, p.j.[email protected]ac.uk. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNanotechnology based advanced therapeutic strategies for targeting interleukins in chronic respiratory diseasesLipopolysaccharide Regulates Pro- and Anti-Inflammatory Cytokines, Corticosterone, and Melatonin in ToadsThe central role of IL-33/IL-1RL1 pathway in asthma: From pathogenesis to interventionAsthma and COVID-19: Emphasis on Adequate of as of and as a Effect of the resistance in asthma: and molecular effects of on a of allergic between and and gene expression of glucocorticoid and receptors from the for of human respiratory with glucocorticoids in the treatment of asthma: of the oral corticosteroids and persistent in from the asthma to bronchial asthma as for A of of Melatonin and Glucocorticoid with in the a between Melatonin and of in Steroid Drug by of proteins during the Efficacy of to in a of corticosteroids in asthma: the between and the novel mode of action of the Association and 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Annals of Internal Medicine · review · 370 citationsread the source →

Policy Actions to Address Weight-Based Bullying and Eating Disorders in Schools: Views of Teachers and School Administrators.

Background: Weight-related bullying is prevalent among youth and associated with adverse health consequences, including increased risk for body dissatisfaction and disordered eating behaviors, which are risk factors for eating disorders. Although concerns about these problems have stimulated calls for broader intervention efforts in schools, actions thus far have been limited. This study examined educators' perspectives about potential policy actions to address these issues in schools. Methods: Educators (N = 240) completed an online questionnaire assessing their support for 11 potential school-based policy actions to address weight-related bullying and eating disorders. Participants also rated policies according to their feasibility and potential for positive impact. Results: Forty-eight percent of participants observed weight-related bullying in their school and 99% expressed the importance of intervening in such incidents. A large majority (75%-94%) supported 8 of the 11 policies, especially actions requiring school-based health curriculum to include content on eating disorder prevention (94%), and addressing weight-bullying through antibullying policies (92%), staff training (89%), and school curriculum (89%). Strongly supported policies were viewed by participants as being the most impactful and feasible to implement. Conclusions: Educators recognize weight-related bullying and eating disorders as problems in their schools that warrant improved prevention and intervention efforts at the policy level.

The Journal of school health · 21 citationsread the source →

A Protocol to Assess Adult Outcomes at 30 Years Following Preterm Birth.

Background: Among the most intense adversity experiences for infants is premature birth. Early birth marks the beginning of a life course that broadly affects families, healthcare, education, social systems, and the survivors themselves. For many, the transition to adulthood is challenging and often hampered by cognitive, physical and mental health, and motor and independence difficulties. Objectives: The aim of this study was to share a comprehensive protocol of a 10th follow-up study of premature infants in their 30s. The protocol accounts for stress during the neonatal period, the cumulative context (risk and protection) of development, biological and epigenetic mechanisms, and individual resilience. Methods: The prospective, five-group longitudinal design includes 215 term-born and preterm-born individuals with various neonatal morbidities at ages 30-35 years. Adult outcomes include health, adaptive, executive function, work, and social competence. Novel measures are four system indicators of allostatic load (AL) and epigenetics. Contextual measures include socioeconomic risk and individual resilience. All measures were selected based on coherence with constructs of the scientific aims, strong psychometrics, continuity for repeated measures, and minimal subject burden. Objective assessments include body composition imaging, exercise testing, blood and saliva collection, and actigraphy. The two-phase protocol takes approximately 8 hours. Discussion: After an 11-month COVID-19 pause, participant response has been strong. As of May 2022, 75 participants have completed the full protocol, and 99 have consented to participate. When socioeconomic risk is controlled, we hypothesize that life course trajectories in physical and psychological health, adaptive function, and executive function will differ between term and preterm neonatal morbidity groups. AL will vary across groups and contribute to outcomes. We expect proximal protection and resilience to mediate the cumulative medical and socioeconomic risk and AL. Epigenome-wide DNA methylation, with estimates of age acceleration, will be examined across groups and explored in longitudinal associations with medical risk, socioeconomic status, and protection. To our knowledge, this is the only U.S. study of premature infants aged 30-35 years. With millions of preterm-born individuals reaching adulthood, the protocol incorporates molecular and genetic biomarkers in a life course developmental examination to inform the timing and content of interventions.

Nursing research · 1 citationsread the source →

Vulnerability to extreme heat by socio-demographic characteristics and area green space among the elderly in Michigan, 1990-2007.

Objectives: We examined how individual and area socio-demographic characteristics independently modified the extreme heat (EH)-mortality association among elderly residents of 8 Michigan cities, May-September, 1990-2007. Methods: In a time-stratified case-crossover design, we regressed cause-specific mortality against EH (indicator for 4-day mean, minimum, maximum or apparent temperature above 97th or 99 th percentiles). We examined effect modification with interactions between EH and personal marital status, age, race, sex and education and ZIP-code percent "non-green space" (National Land Cover Dataset), age, race, income, education, living alone, and housing age (U.S. Census). Results: In models including multiple effect modifiers, the odds of cardiovascular mortality during EH (99 th percentile threshold) vs. non-EH were higher among non-married individuals (1.21, 95% CI=1.14-1.28 vs. 0.98, 95% CI=0.90-1.07 among married individuals) and individuals in ZIP codes with high (91%) non-green space (1.17, 95% CI=1.06-1.29 vs. 0.98, 95% CI=0.89-1.07 among individuals in ZIP codes with low (39%) non-green space). Results suggested that housing age may also be an effect modifier. For the EH-respiratory mortality association, the results were inconsistent between temperature metrics and percentile thresholds of EH but largely insignificant. Conclusions: Green space, housing and social isolation may independently enhance elderly peoples' heat-related cardiovascular mortality vulnerability. Local adaptation efforts should target areas and populations at greater risk.

Environmental research · 84 citationsread the source →

Psychological mechanisms associated with food security status and BMI in adults: a mixed methods study.

Objective: This study examined psychological constructs (delay discounting, grit, future time perspective and subjective social status) in relation to food security status and body weight. Design: A simultaneous triangulation mixed methods design was used to collect quantitative and qualitative data. Quantitative data were collected in fifty-six adults. Independent variables included food security status (food secure or food insecure) and BMI category (normal weight or overweight/obese). Participants, matched on race (African American and White), were categorised into four food security status by BMI category groups. Psychological constructs were measured via validated questionnaires. Qualitative data were collected in a subsample of twelve participants via in-depth interviews. Setting: This study was conducted in Baton Rouge, Louisiana. Participants: The sample was 66 % female and 48 % African American with a mean age of 32·3 (sd 9·2) years and BMI of 28·8 (sd 7·7) kg/m2. Results: Quantitative results showed that food-insecure participants with overweight/obesity had greater delay discounting (-3·78 v. -6·16, P = 0·01; -3·78 v. -5·75, P = 0·02) and poorer grit (3·37 v. 3·99, P = 0·02; 3·37 v. 4·02, P = 0·02 ) than their food-secure counterparts and food-insecure participants with normal weight. Food-insecure participants with overweight/obesity also had a shorter time period for financial planning (0·72 v. 4·14, P = 0·02) than food-secure participants with normal weight. Qualitative data largely supported quantitative findings with participants discussing varied perceptions of psychological constructs. Conclusions: This study found differences in delaying gratification, grit and financial planning between food security status and body weight groups.

Public health nutrition · 11 citationsread the source →

Mind-Body Skills Training for Resident Wellness: A Pilot Study of a Brief Mindfulness Intervention.

Background: Interventions to address burnout include mind-body skills training (MBST), but few studies have evaluated the feasibility of MBST for busy pediatric residents. Objective: In this pilot study, we tested the feasibility of a brief MBST intervention, using in-person peer-led training supported by online modules, to decrease stress and burnout in pediatric resident physicians. Methods: Of 99 (10%) residents, 10 residents at Nationwide Children's Hospital in Ohio participated in up to four 90-minute MBST sessions more than 1 month, led by a co-resident with 5 years of informal training in mind-body skills. Participants were offered 8 assigned online modules through OSU Center for Integrative Health and Wellness. Measures including Maslach Burnout Inventory (MBI), Cohen's Perceived Stress, Smith's Brief Resilience, Cognitive and Affective Mindfulness Scale-Revised, and Neff's Self-Compassion Scale (NSS) were administered before (T1) and after (T2) the course. Participants were offered optional monthly "maintenance" sessions for 6 months and completed a third set of measures at this follow-up (T3). Results: The residents completed an average of 4.3/8 online modules and attended an average of 2.8/4 in-person sessions. There was significant improvement in positive attitude, perceived stress, and resilience post intervention (T2). Follow-up evaluation (T3) also demonstrated significant improvement in burnout (depersonalization) and mindfulness. More than 75% of participants found the course worthwhile. Conclusions: A short mixed-method mindfulness-based skills course may be a practical way to offer resilience and stress management training to busy resident physicians.

Journal of medical education and curricular development · 30 citationsread the source →

Depressive symptoms and objectively measured physical activity and sedentary behaviour throughout adolescence: a prospective cohort study.

Background: Identifying modifiable risk factors is essential to reduce the prevalence adolescent depression. Self-report data suggest that physical activity and sedentary behaviour might be associated with depressive symptoms in adolescents. We examined associations between depressive symptoms and objectively measured physical activity and sedentary behaviour in adolescents. Methods: From a population-based cohort of adolescents whose mothers were invited to participate in the Avon Longitudinal Study of Parents and Children (ALSPAC) study, we included participants with at least one accelerometer recording and a Clinical Interview Schedule-Revised (CIS-R) depression score at age 17·8 years (reported as age 18 years hereafter). Amounts of time spent in sedentary behaviour and physical activity (light or moderate-to-vigorous) were measured with accelerometers at around 12 years, 14 years, and 16 years of age. Total physical activity was also recorded as count per minute (CPM), with raw accelerometer counts averaged over 60 s epochs. Associations between the physical activity and sedentary behaviour variables and depression (CIS-R) scores at age 18 years were analysed with regression and group-based trajectory modelling. Findings: 4257 adolescents from the 14 901 enrolled in the ALSPAC study had a CIS-R depression score at age 18 years. Longitudinal analyses included 2486 participants at age 12 years, 1938 at age 14 years, and 1220 at age 16 years. Total follow-up time was 6 years. Total physical activity decreased between 12 years and 16 years of age, driven by decreasing durations of light activity (mean 325·66 min/day [SD 58·09] at 12 years; 244·94 min/day [55·08] at 16 years) and increasing sedentary behaviour (430·99 min/day [65·80]; 523·02 min/day [65·25]). Higher depression scores at 18 years were associated with a 60 min/day increase in sedentary behaviour at 12 years (incidence rate ratio [IRR] 1·111 [95% CI 1·051-1·176]), 14 years (1·080 [1·012-1·152]), and 16 years of age (1·107 [1·015-1·208]). Depression scores at 18 years were lower for every additional 60 min/day of light activity at 12 years (0·904 [0·850-0·961]), 14 years (0·922 [0·857-0·992]), and 16 years of age (0·889 [0·809-0·974]). Group-based trajectory modelling across 12-16 years of age identified three latent subgroups of sedentary behaviour and activity levels. Depression scores were higher in those with persistently high (IRR 1·282 [95% CI 1·061-1·548]) and persistently average (1·249 [1·078-1·446]) sedentary behaviour compared with those with persistently low sedentary behaviour, and were lower in those with persistently high levels of light activity (0·804 [0·652-0·990]) compared with those with persistently low levels of light activity. Moderate-to-vigorous physical activity (per 15 min/day increase) at age 12 years (0·910 [0·857-0·966]) and total physical activity (per 100 CPM increase) at ages 12 years (0·941 [0·910-0·972]) and 14 years (0·965 [0·932-0·999]), were negatively associated with depressive symptoms. Interpretation: Sedentary behaviour displaces light activity throughout adolescence, and is associated with a greater risk of depressive symptoms at 18 years of age. Increasing light activity and decreasing sedentary behaviour during adolescence could be an important target for public health interventions aimed at reducing the prevalence of depression. Funding: Details of funding are provided in the Acknowledgments.

The lancet. Psychiatry · 211 citationsread the source →

Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians.

To determine the most important drivers of successful ageing at extreme old age, we combined community-based prospective cohorts: Tokyo Oldest Old Survey on Total Health (TOOTH), Tokyo Centenarians Study (TCS) and Japanese Semi-Supercentenarians Study (JSS) comprising 1554 individuals including 684 centenarians and (semi-)supercentenarians, 167 pairs of centenarian offspring and spouses, and 536 community-living very old (85 to 99 years). We combined z scores from multiple biomarkers to describe haematopoiesis, inflammation, lipid and glucose metabolism, liver function, renal function, and cellular senescence domains. In Cox proportional hazard models, inflammation predicted all-cause mortality with hazard ratios (95% CI) 1.89 (1.21 to 2.95) and 1.36 (1.05 to 1.78) in the very old and (semi-)supercentenarians, respectively. In linear forward stepwise models, inflammation predicted capability (10.8% variance explained) and cognition (8(.)6% variance explained) in (semi-)supercentenarians better than chronologic age or gender. The inflammation score was also lower in centenarian offspring compared to age-matched controls with Δ (95% CI) = - 0.795 (- 1.436 to - 0.154). Centenarians and their offspring were able to maintain long telomeres, but telomere length was not a predictor of successful ageing in centenarians and semi-supercentenarians. We conclude that inflammation is an important malleable driver of ageing up to extreme old age in humans.

EBioMedicine · 227 citationsread the source →

Contribution of risk factors to excess mortality in isolated and lonely individuals: an analysis of data from the UK Biobank cohort study.

Background: The associations of social isolation and loneliness with premature mortality are well known, but the risk factors linking them remain unclear. We sought to identify risk factors that might explain the increased mortality in socially isolated and lonely individuals. Methods: We used prospective follow-up data from the UK Biobank cohort study to assess self-reported isolation (a three-item scale) and loneliness (two questions). The main outcomes were all-cause and cause-specific mortality. We calculated the percentage of excess risk mediated by risk factors to assess the extent to which the associations of social isolation and loneliness with mortality were attributable to differences between isolated and lonely individuals and others in biological (body-mass index, systolic and diastolic blood pressure, and handgrip strength), behavioural (smoking, alcohol consumption, and physical activity), socioeconomic (education, neighbourhood deprivation, and household income), and psychological (depressive symptoms and cognitive capacity) risk factors. Findings: 466 901 men and women (mean age at baseline 56·5 years [SD 8·1]) were included in the analyses, with a mean follow-up of 6·5 years (SD 0·8). The hazard ratio for all-cause mortality for social isolation compared with no social isolation was 1·73 (95% CI 1·65-1·82) after adjustment for age, sex, ethnic origin, and chronic disease (ie, minimally adjusted), and was 1·26 (95% CI 1·20-1·33) after further adjustment for socioeconomic factors, health-related behaviours, depressive symptoms, biological factors, cognitive performance, and self-rated health (ie, fully adjusted). The minimally adjusted hazard ratio for mortality risk related to loneliness was 1·38 (95% CI 1·30-1·47), which reduced to 0·99 (95% CI 0·93-1·06) after full adjustment for baseline risks. Interpretation: Isolated and lonely people are at increased risk of death. Health policies addressing risk factors such as adverse socioeconomic conditions, unhealthy lifestyle, and lower mental wellbeing might reduce excess mortality among the isolated and the lonely. Funding: Academy of Finland, NordForsk, and the UK Medical Research Council.

The Lancet. Public health · 295 citationsread the source →

Use and Effect of Embodied Conversational Agents for Improving Eating Behavior and Decreasing Loneliness Among Community-Dwelling Older Adults: Randomized Controlled Trial.

Background: Embodied conversational agents (ECAs) have been proposed as a promising interaction modality for the delivery of programs focused on promoting lifestyle changes. However, it is not understood what factors influence the health effects of ECAs or their use. Objective: We aimed to (1) identify whether ECAs could persuade community-dwelling older adults to change their dietary behavior and whether ECA use could decrease loneliness, (2) test the pathways to these effects, and (3) understand factors influencing the use of ECAs. Methods: A randomized controlled trial was conducted. The intervention group received access to the PACO service for 8 weeks. The waitlist group started PACO use after waiting for 4 weeks. Two primary outcomes (eating behavior and loneliness) were assessed via online questionnaires at intake, upon joining the waitlist, after 4 weeks, and after 8 weeks. The third primary outcome (use) was assessed via data logs. Secondary outcomes were measured at the same time points, via questionnaires or an optional interview. Results: In total, 32 participants completed the intervention. We found a significant correlation between use in minutes on the one hand, and perceived usefulness (r=0.39, P=.03) and enjoyment on the other (r=0.38, P=.03). However, these did not predict use in the full regression model (F2,29=1.98, P=.16, R2=0.12). Additionally, PACO use did not lead to improvement in eating behavior (χ22=0.34, P=.85) or a decrease in loneliness (χ22=0.02, P=.99). Conclusions: Our study did not provide any concluding evidence about factors that are linked to the use or health effects of ECAs. Future service design could benefit from either creating a functional design catering to the predominant stage in the precaution adoption process model of the targeted population, or by personalizing the service based on an intake in which the end user's stage is determined. Trial registration: ClinicalTrials.gov NCT04510883; https://clinicaltrials.gov/ct2/show/NCT04510883. International registered report identifier (irrid): RR2-10.2196/22186.

JMIR formative research · 15 citationsread the source →

Roles of cyberbullying, sleep, and physical activity in mediating the effects of social media use on mental health and wellbeing among young people in England: a secondary analysis of longitudinal data.

Background: There is growing concern about the potential associations between social media use and mental health and wellbeing in young people. We explored associations between the frequency of social media use and later mental health and wellbeing in adolescents, and how these effects might be mediated. Methods: We did secondary analyses of publicly available data from the Our Futures study, a nationally representative, longitudinal study of 12 866 young people from age 13 years to 16 years in England. The exposure considered was the frequency of social media use (from weekly or less to very frequent [multiple times daily]) at wave 1 (participants aged 13-14 years) through wave 3 of the study (participants aged 15-16 years). Outcomes were mental health at wave 2 (with high 12-item General Health Questionnaire [GHQ12] scores [≥3] indicating psychological distress), and wellbeing at wave 3 (life satisfaction, feeling life is worthwhile, happiness, and anxiety, rated from 1 to 10 by participants). Analyses were adjusted for a minimal sufficient confounding structure, and were done separately for boys and girls. Cyberbullying, sleep adequacy, and physical activity were assessed as potential mediators of the effects. Findings: Very frequent use of social media increased from wave 1 to wave 3: from 34·4% (95% CI 32·4-36·4) to 61·9% (60·3-63·6) in boys, and 51·4% (49·5-53·3) to 75·4% (73·8-76·9) in girls. Very frequent social media use in wave 1 predicted a high GHQ12 score at wave 2 among girls (adjusted odds ratio [OR] 1·31 [95% CI 1·06-1·63], p=0·014; N=4429) and boys (1·67 [1·24-2·26], p=0·0009; N=4379). Persistent very frequent social media use across waves 1 and 2 predicted lower wellbeing among girls only (adjusted ORs 0·86 [0·74-0·99], N=3753, p=0·039 for life satisfaction; 0·80 [0·70-0·92], N=3831, p=0·0013 for happiness; 1·28 [1·11-1·48], N=3745, p=0·0007 for anxiety). Adjustment for cyberbullying, sleep, and physical activity attenuated the associations of social media use with GHQ12 high score (proportion mediated 58·2%), life satisfaction (80·1%), happiness (47·7%), and anxiety (32·4%) in girls, such that these associations (except for anxiety) were no longer significant; however, the association with GHQ12 high score among boys remained significant, being mediated only 12·1% by these factors. Interpretation: Mental health harms related to very frequent social media use in girls might be due to a combination of exposure to cyberbullying or displacement of sleep or physical activity, whereas other mechanisms appear to be operative in boys. Interventions to promote mental health should include efforts to prevent or increase resilience to cyberbullying and ensure adequate sleep and physical activity in young people. Funding: None.

The Lancet. Child & adolescent health · 131 citationsread the source →

Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines.

Background: We hypothesize that left-sided low-level vagus nerve stimulation (LL-VNS) can suppress sympathetic outflow and reduce atrial tachyarrhythmias in ambulatory dogs. Methods and results: We implanted a neurostimulator in 12 dogs to stimulate the left cervical vagus nerve and a radiotransmitter for continuous recording of left stellate ganglion nerve activity, vagal nerve activities, and ECGs. Group 1 dogs (N=6) underwent 1 week of continuous LL-VNS. Group 2 dogs (N=6) underwent intermittent rapid atrial pacing followed by active or sham LL-VNS on alternate weeks. Integrated stellate ganglion nerve activity was significantly reduced during LL-VNS (7.8 mV/s; 95% confidence interval [CI] 6.94 to 8.66 versus 9.4 mV/s [95% CI, 8.5 to 10.3] at baseline; P=0.033) in group 1. The reduction was most apparent at 8 am, along with a significantly reduced heart rate (P=0.008). Left-sided low-level vagus nerve stimulation did not change vagal nerve activity. The density of tyrosine hydroxylase-positive nerves in the left stellate ganglion 1 week after cessation of LL-VNS were 99 684 μm(2)/mm(2) (95% CI, 28 850 to 170 517) in LL-VNS dogs and 186 561 μm(2)/mm(2) (95% CI, 154 956 to 218 166; P=0.008) in normal dogs. In group 2, the frequencies of paroxysmal atrial fibrillation and tachycardia during active LL-VNS were 1.4/d (95% CI, 0.5 to 5.1) and 8.0/d (95% CI, 5.3 to 12.0), respectively, significantly lower than during sham stimulation (9.2/d [95% CI, 5.3 to 13.1]; P=0.001 and 22.0/d [95% CI, 19.1 to 25.5], P<0.001, respectively). Conclusions: Left-sided low-level vagus nerve stimulation suppresses stellate ganglion nerve activities and reduces the incidences of paroxysmal atrial tachyarrhythmias in ambulatory dogs. Significant neural remodeling of the left stellate ganglion is evident 1 week after cessation of continuous LL-VNS.

Circulation · 180 citationsread the source →

Socio-demographic characteristics of children infested with scabies in densely populated communities of residential madrashas (Islamic education institutes) in Dhaka, Bangladesh.

Background: Outbreaks of scabies in institutions and the socio-economic consequences have not been reported from overpopulated countries such as Bangladesh. Study design: A community-based study among children from six residential Islamic education institutes (madrashas) in Dhaka. Multistage random sampling was used. Objectives: To study the socio-economic profile, water-sanitation facilities, personal hygiene and living conditions of these children. Methodology: Direct interviews were used to collect the data and clinical check up was performed in all children. Results: In total, 492 children received clinical check-ups; 92.5% were boys (mean age: 11.2+/-2.4 years). 63.4% of fathers and 98.5% of mothers were either illiterate or had only received primary education, 55.1% of fathers were in low-paid labouring jobs, and 99% of mothers were housewives. Of the 98% of children who had scabies, 71% had been re-infected (96% during the winter). Randomly assigned anti-scabies drugs revealed an average cure rate of 85.5%. Seventy-four percent of children were living in poorly ventilated buildings with overcrowded sleeping arrangements. They had poor personal hygiene: 21% shared towels; 8% shared undergarments; 30% shared bed linen; and 81% kept their used clothes on a communal line or shelf. Sanitation was also poor: 39% bathed infrequently, although 97% carried out mandatory ablution. Most children (61%) washed their clothes (including undergarments) two or three times a fortnight, 35% did so every 2-3 days, and 3.7% washed their clothes on alternative days. Disease severity and re-infection were associated with infrequent washing of clothes (P<0.001) and bed linen (P<0.001), overcrowded sleeping arrangements (P<0.001) and infrequent bathing (P<0.001) with soap (P<0.001). This was further related to household income (P<0.001 for both). Conclusion: The study findings have potentially dangerous implications for public health. Immediate attention should be given to developing a sustainable long-term intervention programme to combat scabies hyperendemicity, and to save thousands of children from impending complications.

Public health · 23 citationsread the source →

Direct and indirect effects of religiosity on valuation of life through forgiveness and social provisions among older incarcerated males.

Purpose of the study: Few studies have investigated the influence of religiosity (REL), forgiveness, and social resources on incarcerated individuals' attachment to their lives, or valuation of life (VOL). We tested a model linking REL to VOL through 3 subscales of the Heartland Forgiveness Scale (Self, Others, and Situations) and social provisions (SPS). Design and methods: Cross-sectional data were collected from 261 male prison inmates, aged 45-82, incarcerated in 8 state-managed correctional facilities. Participants were sampled from the prison census database (Oklahoma Department of Corrections or DOC). Exclusion criteria, per the Oklahoma DOC, were those housed in medical or psychiatric units, currently in solitary confinement, or sentenced to death row. Results: To account for possible violations of multivariate normality, we used the Satorra-Bentler chi-square statistic. The final model fit the data well, explaining 57% of the variance in VOL: χ(2) (N = 261; df = 3) = 7.40; p = .06; Comparative Fit Index = .99; root mean squared error of approximation = .08; standardized root mean squared residual = .02. Significant indirect effects of REL on VOL were present through Forgiveness of Others and SPS, and of REL on SPS through Forgiveness of Others. Analyses controlled for age, race, education, perceived physical health, and depressive symptoms. Implications: Implications of the findings for those involved with prisoner care are discussed, particularly therapeutic interventions including process models of forgiveness.

The Gerontologist · 16 citationsread the source →

Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study.

Objectives: To provide a global, up-to-date picture of the prevalence, treatment, and outcomes of Candida bloodstream infections in intensive care unit patients and compare Candida with bacterial bloodstream infection. Design: A retrospective analysis of the Extended Prevalence of Infection in the ICU Study (EPIC II). Demographic, physiological, infection-related and therapeutic data were collected. Patients were grouped as having Candida, Gram-positive, Gram-negative, and combined Candida/bacterial bloodstream infection. Outcome data were assessed at intensive care unit and hospital discharge. Setting: EPIC II included 1265 intensive care units in 76 countries. Patients: Patients in participating intensive care units on study day. Interventions: None. Measurement and main results: Of the 14,414 patients in EPIC II, 99 patients had Candida bloodstream infections for a prevalence of 6.9 per 1000 patients. Sixty-one patients had candidemia alone and 38 patients had combined bloodstream infections. Candida albicans (n = 70) was the predominant species. Primary therapy included monotherapy with fluconazole (n = 39), caspofungin (n = 16), and a polyene-based product (n = 12). Combination therapy was infrequently used (n = 10). Compared with patients with Gram-positive (n = 420) and Gram-negative (n = 264) bloodstream infections, patients with candidemia were more likely to have solid tumors (p < .05) and appeared to have been in an intensive care unit longer (14 days [range, 5-25 days], 8 days [range, 3-20 days], and 10 days [range, 2-23 days], respectively), but this difference was not statistically significant. Severity of illness and organ dysfunction scores were similar between groups. Patients with Candida bloodstream infections, compared with patients with Gram-positive and Gram-negative bloodstream infections, had the greatest crude intensive care unit mortality rates (42.6%, 25.3%, and 29.1%, respectively) and longer intensive care unit lengths of stay (median [interquartile range]) (33 days [18-44], 20 days [9-43], and 21 days [8-46], respectively); however, these differences were not statistically significant. Conclusion: Candidemia remains a significant problem in intensive care units patients. In the EPIC II population, Candida albicans was the most common organism and fluconazole remained the predominant antifungal agent used. Candida bloodstream infections are associated with high intensive care unit and hospital mortality rates and resource use.

Critical care medicine · 276 citationsread the source →

Taking a Spiritual History Allows Clinicians to Understand Patients More Fully

Journal of Palliative MedicineVol. 3, No. 1 Innovations in End-of-Life CareTaking a Spiritual History Allows Clinicians to Understand Patients More FullyDr. Christina Puchalski and Anna L. RomerDr. Christina Puchalski and Anna L. RomerPublished Online:19 Apr 2005https://doi.org/10.1089/jpm.2000.3.129AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byVerbalizing spiritual needs in palliative care: a qualitative interview study on verbal and non-verbal communication in two Danish hospices4 January 2022 | BMC Palliative Care, Vol. 21, No. 1Implementation of an Educational Toolkit to Increase Nurse Competence in Spirituality and Spiritual Care of Oncology Patients8 November 2022 | Journal of Holistic Nursing, Vol. 5Posicionamento sobre a Saúde Cardiovascular nas Mulheres – 2022Arquivos Brasileiros de Cardiologia, Vol. 119, No. 5Experiences of German health care professionals with spiritual history taking in primary care: a mixed-methods process evaluation of the HoPES3 intervention15 October 2022 | Family Practice, Vol. 29Religious and spiritual journeys of LGBT older adults in rural Southern Appalachia25 October 2021 | Journal of Religion, Spirituality & Aging, Vol. 34, No. 4The CASH assessment tool: A window into existential suffering19 May 2021 | Journal of Health Care Chaplaincy, Vol. 28, No. 4Integrating religion/spirituality into professional social work practice27 July 2022 | Journal of Religion & Spirituality in Social Work: Social Thought, Vol. 41, No. 4The Concept of Spirituality in the Health Sector: Contributions from the Study of Religion27 September 2022 | International Journal of Latin American Religions, Vol. 12Systematic review: The relationship between religion, spirituality and mental health in adolescents who identify as transgender13 September 2022 | Journal of Gay & Lesbian Mental Health, Vol. 26„Des Lebens Ruf an uns wird niemals enden“ – Sinnzentrierte Interventionen im Überblick30 August 2022 | Zeitschrift für Palliativmedizin, Vol. 23, No. 05Case discussion: The critically ill older adult in spiritual distressGeriatric Nursing, Vol. 47Australian Patient Preferences for the Introduction of Spirituality into their Healthcare Journey: A Mixed Methods Study3 August 2022 | Journal of Religion and Health, Vol. 27Religion, Spirituality, and Ethics in Psychiatric Practice30 March 2022 | Journal of Nervous & Mental Disease, Vol. 210, No. 8Spiritual distress in dialysis: A case report21 July 2022 | Progress in Palliative Care, Vol. 211Interprofessional communication training to address spiritual aspects of cancer care19 July 2022 | Journal of Health Care Chaplaincy, Vol. 29Spirituality in Serious Illness and HealthJAMA, Vol. 328, No. 2What is the role of spiritual care specialists in teaching generalist spiritual care? 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Psikoterapilerdeki Dini İzler15 December 2018 | Cumhuriyet İlahiyat Dergisi, Vol. 22, No. 3Women's Perceptions of Using Short Films to Integrate Spirituality in TherapyJournal of Systemic Therapies, Vol. 37, No. 4Content Validation of Advanced Illness Criteria of a Palliative Care Screening Tool Lauren C. DiLello, Karen Mulvihill, Jennifer Delli Carpini, Riddhi Shah, Julia Hermanowski, and Damanjeet Chaubey29 October 2018 | Journal of Palliative Medicine, Vol. 21, No. 11Understanding, assessing, and in the spiritual of medical and October 2018 | Theology, Vol. 11, No. and of in Living with October 2018 | Journal of & Social Services, Vol. No. for the spirituality as October 2018 | Revista de Vol. 71, No. An of an aged psychiatry March 2018 | Psychiatry, Vol. 26, No. de de vida de de Vol. 25, No. support and with in Care in the Care A Narrative June | Journal of Care Medicine, Vol. No. Care in Cancer: in the of of Clinical Oncology Educational Vol. 3, No. religion/spirituality in clinical practice: A among social and and October | Journal of Clinical Psychology, Vol. 74, No. Spirituality in Care December | Journal of Religion and Health, Vol. 57, No. of to spiritual care at the of a phenomenological exploration from the of palliative care February 2018 | Journal for the Study of Spirituality, Vol. 8, No. Existential Distress in Pediatric Cancer December and Patient Spiritual in the through October of Spirituality in November Psychological/Psychiatric, Social, and Spiritual Problems and July and End-of-Life Care in Cancer in Oncology Nursing, Vol. No. Care in Hospice and Palliative Journal of Hospice and Palliative Care, Vol. 20, No. and Spirituality: Literature review and Journal of Counseling, Vol. 18, No. of the tool existential communication between and cancer August | European Journal of General Practice, Vol. 23, No. Education and of Christian Nursing, Vol. 34, No. Care Interventions in to and Therapy C. and D. September | Journal of Palliative Medicine, Vol. 20, No. in Patients with A Qualitative September | Journal of Research in Nursing and Vol. 14, No. theory on the and in an exploratory case study September | Vol. 69, No. of the of Spirituality and Palliative Care Research and of Pain and Symptom Management, Vol. No. of a spiritual care training program for staff on November | Palliative and Supportive Care, Vol. 15, No. 4Spiritual distress and spiritual care in advanced heart July | Reviews, Vol. and Spiritual Patient Simulation in Nursing, Vol. No. Vol. 42, No. 4The impact of a spiritual in patients with and and their support December | Vol. 26, No. 3The Importance of a Spiritual History in Healthcare Vol. No. About Substance Use DisordersJournal of Psychosocial Nursing and Mental Health Services, Vol. No. and Spiritual Beliefs of April | Journal of Religion and Health, Vol. No. Care Perceptions of and With of Hospice & Palliative Nursing, Vol. 19, No. in Substance Use What to Know to Practice30 November | in Mental Health Nursing, Vol. 38, No. End-of-Life Care to Religious and Vol. No. of Social Education, Vol. 53, No. Nursing Care and of Christian Nursing, Vol. 34, No. 1The of taking a religious and spiritual July | Psychiatry, Vol. 24, No. religion and spirituality in Vol. No. the role of religious in the at the of of Vol. No. care spiritual March | Supportive Care in Cancer, Vol. 24, No. Spiritual Care and the Role of An Review of Literature and April | Journal of Religion and Health, Vol. No. of the Spiritual Needs of of with Is in the June | Journal of Palliative Medicine, Vol. 19, No. Impact of a Tool for Comprehensive Assessment of Palliative Care on Assessment at and of Pain and Symptom Management, Vol. No. from Healthcare Students to Understand Spiritual Assessment in Clinical Practice29 October | Journal of Religion and Health, Vol. No. Spirituality in January | Journal of Religion and Health, Vol. No. 3Development and of to Assess Nurse Provision of Spiritual August 2014 | Journal of Holistic Nursing, Vol. 34, No. and Validation of the Practice Assessment September 2014 | Research on Social Practice, Vol. 26, No. and the Medical A of July | Journal of Health Care Chaplaincy, Vol. 22, No. history taking in palliative care: A controlled September | Palliative Medicine, Vol. 30, No. Is Is Using A and the Life With American in Spiritual March | Journal of in Mental Health, Vol. 11, No. and spiritual in September | International Journal of and Mental Health, Vol. No. 1The of Hospital to and Patients’ Spiritual A May | Journal for the Study of Spirituality, Vol. No. 1The and to March End-of-Life Spiritual March in Holistic Patient Journal of Nursing, Vol. No. of spiritual assessment for older September 2014 | and Vol. No. und der der Care, Vol. No. Spirituality and A for Holistic January | Journal of Religion and Health, Vol. No. and Belief, in Care spiritual history tool by C. M. Puchalski as an for an interdisciplinary in January | Journal for of and Social Vol. 21, No. the of Spiritual A Pain and Palliative Care Service Quality of Pain and Symptom Management, Vol. No. of Spiritual Assessment in September | Vol. No. the of Christian Nursing, Vol. 32, No. 4Spiritual care: is the assessment tool for palliative Journal of Palliative Nursing, Vol. 21, No. und Spiritualität in der September | Vol. 60, No. of September of spirituality assessment in palliative care patients in November 2014 | Progress in Palliative Care, Vol. 23, No. 4The for Spiritual A Mixed-Methods July | Oncology Nursing Vol. 42, No. 4The Integration of Religion and Spirituality in Social Practice: A May | Social Vol. 60, No. 3The and Educational of a Spiritual Life Review for Patients with and June 2014 | Journal of Cancer Education, Vol. 30, No. in Geriatric Palliative in Geriatric Medicine, Vol. No. An for Spiritual Well-Being May | Journal of Religion & Spirituality in Social Work: Social Thought, Vol. 34, No. Spiritual Assessment March | Journal of Health Care Chaplaincy, Vol. 21, No. American on Mental Health, and Help April | and Vol. 60, No. of Christian Nursing, Vol. 32, No. the Spiritual Needs and of Oncology Patients in Nursing Practice, Vol. 29, No. Care Training to Healthcare Professionals: A Systematic April | Journal of Pastoral Care & Counseling: Advancing theory and professional practice through scholarly and reflective publications, Vol. 69, No. analysis of spiritual

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