Objective:The primary aim of this study was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first-episode psychosis designed for ...implementation in the U.S. health care system, with community care on quality of life.Method:Thirty-four clinics in 21 states were randomly assigned to NAVIGATE or community care. Diagnosis, duration of untreated psychosis, and clinical outcomes were assessed via live, two-way video by remote, centralized raters masked to study design and treatment. Participants (mean age, 23) with schizophrenia and related disorders and ≤6 months of antipsychotic treatment (N=404) were enrolled and followed for ≥2 years. The primary outcome was the total score of the Heinrichs-Carpenter Quality of Life Scale, a measure that includes sense of purpose, motivation, emotional and social interactions, role functioning, and engagement in regular activities.Results:The 223 recipients of NAVIGATE remained in treatment longer, experienced greater improvement in quality of life and psychopathology, and experienced greater involvement in work and school compared with 181 participants in community care. The median duration of untreated psychosis was 74 weeks. NAVIGATE participants with duration of untreated psychosis of <74 weeks had greater improvement in quality of life and psychopathology compared with those with longer duration of untreated psychosis and those in community care. Rates of hospitalization were relatively low compared with other first-episode psychosis clinical trials and did not differ between groups.Conclusions:Comprehensive care for first-episode psychosis can be implemented in U.S. community clinics and improves functional and clinical outcomes. Effects are more pronounced for those with shorter duration of untreated psychosis.
Comprehensive coordinated specialty care programs for first-episode psychosis have been widely implemented in other countries but not in the United States. The National Institute of Mental Health’s ...Recovery After an Initial Schizophrenia Episode (RAISE) initiative focused on the development and evaluation of first-episode treatment programs designed for the U.S. health care system. This article describes the background, rationale, and nature of the intervention developed by the RAISE Early Treatment Program project—known as the NAVIGATE program—with a particular focus on its psychosocial components. NAVIGATE is a team-based, multicomponent treatment program designed to be implemented in routine mental health treatment settings and aimed at guiding people with a first episode of psychosis (and their families) toward psychological and functional health. The core services provided in the NAVIGATE program include the family education program (FEP), individual resiliency training (IRT), supported employment and education (SEE), and individualized medication treatment. NAVIGATE embraces a shared decision-making approach with a focus on strengths and resiliency and on collaboration with clients and family members in treatment planning and reviews. The NAVIGATE program has the potential to fill an important gap in the U.S. health care system by providing a comprehensive intervention specially designed to meet the unique treatment needs of persons recovering from a first episode of psychosis. A cluster-randomized controlled trial comparing NAVIGATE with usual community care has recently been completed.
HIV risk remains unacceptably high among adolescent girls and young women (AGYW) in southern and eastern Africa, reflecting structural and social inequities that drive new infections. In 2015, PEPFAR ...(the United States President's Emergency Plan for AIDS Relief) with private-sector partners launched the DREAMS Partnership, an ambitious package of interventions in 10 sub-Saharan African countries. DREAMS aims to reduce HIV incidence by 40% among AGYW over two years by addressing multiple causes of AGYW vulnerability. This protocol outlines an impact evaluation of DREAMS in four settings.
To achieve an impact evaluation that is credible and timely, we describe a mix of methods that build on longitudinal data available in existing surveillance sites prior to DREAMS roll-out. In three long-running surveillance sites (in rural and urban Kenya and rural South Africa), the evaluation will measure: (1) population-level changes over time in HIV incidence and socio-economic, behavioural and health outcomes among AGYW and young men (before, during, after DREAMS); and (2) causal pathways linking uptake of DREAMS interventions to 'mediators' of change such as empowerment, through to behavioural and health outcomes, using nested cohort studies with samples of ~ 1000-1500 AGYW selected randomly from the general population and followed for two years. In Zimbabwe, where DREAMS includes an offer of pre-exposure HIV prophylaxis (PrEP), cohorts of young women who sell sex will be followed for two years to measure the impact of 'DREAMS+PrEP' on HIV incidence among young women at highest risk of HIV. In all four settings, process evaluation and qualitative studies will monitor the delivery and context of DREAMS implementation. The primary evaluation outcome is HIV incidence, and secondary outcomes include indicators of sexual behavior change, and social and biological protection.
DREAMS is, to date, the most ambitious effort to scale-up combinations or 'packages' of multi-sectoral interventions for HIV prevention. Evidence of its effectiveness in reducing HIV incidence among AGYW, and demonstrating which aspects of the lives of AGYW were changed, will offer valuable lessons for replication.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Patients with high blood pressure (hypertension) in the community frequently fail to meet treatment goals ‐ a condition labelled as "uncontrolled" hypertension. The optimal way to organize ...and deliver care to hypertensive patients has not been clearly identified.
Objectives
To determine the effectiveness of interventions to improve control of blood pressure in patients with hypertension. To evaluate the effectiveness of reminders on improving the follow‐up of patients with hypertension.
Search methods
All‐language search of all articles (any year) in the Cochrane Controlled Trials Register (CCTR) and Medline; and Embase from January 1980.
Selection criteria
Randomized controlled trials (RCTs) of patients with hypertension that evaluated the following interventions:
(1) self‐monitoring
(2) educational interventions directed to the patient
(3) educational interventions directed to the health professional
(4) health professional (nurse or pharmacist) led care
(5) organisational interventions that aimed to improve the delivery of care
(6) appointment reminder systems
Outcomes assessed were:
(1) mean systolic and diastolic blood pressure
(2) control of blood pressure
(3) proportion of patients followed up at clinic
Data collection and analysis
Two authors extracted data independently and in duplicate and assessed each study according to the criteria outlined by the Cochrane Handbook.
Main results
72 RCTs met our inclusion criteria. The methodological quality of included studies varied. An organized system of regular review allied to vigorous antihypertensive drug therapy was shown to reduce systolic blood pressure (weighted mean difference (WMD) ‐8.0 mmHg, 95% CI: ‐8.8 to ‐7.2 mmHg) and diastolic blood pressure (WMD ‐4.3 mmHg, 95% CI: ‐4.7 to ‐3.9 mmHg) for three strata of entry blood pressure, and all‐cause mortality at five years follow‐up (6.4% versus 7.8%, difference 1.4%) in a single large RCT‐ the Hypertension Detection and Follow‐Up study. Other interventions had variable effects. Self‐monitoring was associated with moderate net reduction in systolic blood pressure (WMD ‐2.5 mmHg, 95% CI: ‐3.7 to ‐1.3 mmHg) and diastolic blood pressure (WMD ‐1.8 mmHg, 95% CI: ‐2.4 to ‐1.2 mmHg). RCTs of educational interventions directed at patients or health professionals were heterogeneous but appeared unlikely to be associated with large net reductions in blood pressure by themselves. Nurse or pharmacist led care may be a promising way forward, with the majority of RCTs being associated with improved blood pressure control and mean SBP and DBP but these interventions require further evaluation. Appointment reminder systems also require further evaluation due to heterogeneity and small trial numbers, but the majority of trials increased the proportion of individuals who attended for follow‐up (odds ratio 0.41, 95% CI 0.32 to 0.51) and in two small trials also led to improved blood pressure control, odds ratio favouring intervention 0.54 (95% CI 0.41 to 0.73).
Authors' conclusions
Family practices and community‐based clinics need to have an organized system of regular follow‐up and review of their hypertensive patients. Antihypertensive drug therapy should be implemented by means of a vigorous stepped care approach when patients do not reach target blood pressure levels. Self‐monitoring and appointment reminders may be useful adjuncts to the above strategies to improve blood pressure control but require further evaluation.
Omentin Plasma Levels and Gene Expression Are Decreased in Obesity
Celia M. de Souza Batista 1 2 ,
Rong-Ze Yang 1 ,
Mi-Jeong Lee 1 ,
Nicole M. Glynn 1 ,
Dao-Zhan Yu 1 ,
Jessica Pray 1 ,
Kelechi ...Ndubuizu 3 ,
Susheel Patil 4 ,
Alan Schwartz 4 ,
Mark Kligman 5 ,
Susan K. Fried 1 6 ,
Da-Wei Gong 1 2 ,
Alan R. Shuldiner 1 2 6 ,
Toni I. Pollin 1 and
John C. McLenithan 1 2 6
1 Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore,
Maryland
2 Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland
3 Department of Biology, University of Maryland Baltimore County, Baltimore, Maryland
4 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
5 Division of General Surgery, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland
6 Geriatric Research, Education and Clinical Center, Baltimore Veterans Affairs Medical Center, Baltimore, Maryland
Address correspondence and reprint requests to John C. McLenithan, 660 West Redwood St., Room 490, Baltimore, MD 21201. E-mail:
jmcle001{at}umaryland.edu
Abstract
Central obesity and the accumulation of visceral fat are risk factors for the development of type 2 diabetes and cardiovascular
disease. Omentin is a protein expressed and secreted from visceral but not subcutaneous adipose tissue that increases insulin
sensitivity in human adipocytes. To determine the impact of obesity-dependent insulin resistance on the regulation of two
omentin isoforms, gene expression and plasma levels were measured in lean, overweight, and obese subjects. Omentin 1 was shown
to be the major circulating isoform in human plasma. Lean subjects had significantly higher plasma omentin 1 levels than obese
and overweight subjects. In addition, higher plasma omentin 1 levels were detected in women compared with men. Plasma omentin
1 levels were inversely correlated with BMI, waist circumference, leptin levels, and insulin resistance as measured by homeostasis
model assessment and positively correlated with adiponectin and HDL levels. Both omentin 1 and omentin 2 gene expression were
decreased with obesity and were highly correlated with each other in visceral adipose tissue. In summary, decreased omentin
levels are associated with increasing obesity and insulin resistance. Therefore, omentin levels may be predictive of the metabolic
consequences or co-morbidities associated with obesity.
AFDS, Amish Family Diabetes Study
HOMA, homeostasis model assessment
pI, isoelectric point
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 28 February 2007. DOI: 10.2337/db06-1506.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted February 20, 2007.
Received October 26, 2006.
DIABETES
Few studies have examined multiple risk factors for mortality or formally compared their associations across specific causes of death. The authors used competing risks survival analysis to evaluate ...associations of lifestyle and dietary factors with all-cause and cause-specific mortality among 50,112 participants in the Nurses' Health Study. There were 4,893 deaths between 1986 and 2004: 1,026 from cardiovascular disease, 931 from smoking-related cancers, 1,430 from cancers not related to smoking, and 1,506 from all other causes. Age, body mass index at age 18 years, weight change, height, current smoking and pack-years of smoking, glycemic load, cholesterol intake, systolic blood pressure and use of blood pressure medications, diabetes, parental myocardial infarction before age 60 years, and time since menopause were directly related to all-cause mortality, whereas there were inverse associations for physical activity and intakes of nuts, polyunsaturated fat, and cereal fiber. Moderate alcohol consumption was associated with decreased mortality. A model that incorporated differences in the associations of some risk factors with specific causes of death had a significantly better fit compared with a model in which all risk factors had common associations across all causes. In the future, this new model may be used to identify individuals at increased risk of mortality.
Drug use for or during sex (‘chemsex’) among MSM has caused concern, because of the direct effects of the drugs themselves, and because of an increased risk of transmission of sexually transmitted ...infections (STIs). This study aimed to assess the prevalence of chemsex, associated behaviours and STIs among attendees at Ireland’s only MSM-specific sexual health clinic in Dublin over a six week period in 2016.
The questionnaire collected demographic data, information on sexuality and sexual practice, self-reported history of treatment for STIs, and chemsex use. Key variables independently associated with treatment for STIs over the previous 12 months were identified using multivariable logistic regression.
The response rate was 90% (510/568). One in four (27%) reported engaging in chemsex within the previous 12 months. Half had taken ≥2 drugs on his last chemsex occasion. One in five (23%) reported that they/their partners had lost consciousness as a result of chemsex. Those engaging in chemsex were more likely to have had more sexual partners(p<0.001), more partners for anal intercourse (p<0.001) and to have had condomless anal intercourse(p=0.041). They were also more likely to report having been treated for gonorrhoea over the previous 12 months (adjusted OR 2.03, 95% CI 1.19–3.46, p=0.009). One in four (25%) reported that chemsex was impacting negatively on their lives and almost one third (31%) reported that they would like help or advice about chemsex.
These results support international evidence of a chemsex culture among a subset of MSM. They will be used to develop an effective response which simultaneously addresses addiction and sexual ill-health among MSM who experience harm/seek help as a consequence of engagement in chemsex.
Since 1999, nucleic acid–amplification testing has been used in the United States to identify units of blood from donors with viremia in the window period before seroconversion. This approach ...identifies approximately 1 unit infected with human immunodeficiency virus type 1 (HIV-1) among 3.1 million units screened and 1 infected with hepatitis C virus (HCV) among 230,000 units screened.
Nucleic acid–amplification testing prevents about 5 cases of transfusion-transmitted HIV-1 infection and 56 of HCV infection per year.
Screening of potential blood donors has historically relied on the use of immunoassays to detect viral antibodies or antigens. In 1999, new screening methods involving nucleic acid amplification to detect human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA were implemented in the United States under an investigational new drug protocol approved by the Food and Drug Administration (FDA).
1
–
3
This new technique was used to test multiple samples in small pools, referred to as “minipools.” The decision to implement this technique was based on its ability to identify HIV-1– and HCV-infected donors early in the infectious . . .
A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We ...evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.
This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674.
Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 0·6% of 4440 in the ChAdOx1 nCoV-19 group vs71 1·6% of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three 0·2% of 1367 vs 30 2·2% of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 0·5% of 5807 vs 101 1·7% of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation.
ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.
UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
Purpose Decision models are time-consuming to develop; therefore, adapting previously developed models for new purposes may be advantageous. We provide methods to prioritize efforts to 1) update ...parameter values in existing models and 2) adapt existing models for distributional cost-effectiveness analysis (DCEA). Methods Methods exist to assess the influence of different input parameters on the results of a decision models, including value of information (VOI) and 1-way sensitivity analysis (OWSA). We apply 1) VOI to prioritize searches for additional information to update parameter values and 2) OWSA to prioritize searches for parameters that may vary by socioeconomic characteristics. We highlight the assumptions required and propose metrics that quantify the extent to which parameters in a model have been updated or adapted. We provide R code to quickly carry out the analysis given inputs from a probabilistic sensitivity analysis (PSA) and demonstrate our methods using an oncology case study. Results In our case study, updating 2 of 21 probabilistic model parameters addressed 71.5% of the total VOI and updating 3 addressed approximately 100% of the uncertainty. Our proposed approach suggests that these are the 3 parameters that should be prioritized. For model adaptation for DCEA, 46.3% of the total OWSA variation came from a single parameter, while the top 10 input parameters were found to account for more than 95% of the total variation, suggesting efforts should be aimed toward these. Conclusions These methods offer a systematic approach to guide research efforts in updating models with new data or adapting models to undertake DCEA. The case study demonstrated only very small gains from updating more than 3 parameters or adapting more than 10 parameters. Highlights It can require considerable analyst time to search for evidence to update a model or to adapt a model to take account of equity concerns. In this article, we provide a quantitative method to prioritze parameters to 1) update existing models to reflect potential new evidence and 2) adapt existing models to estimate distributional outcomes. We define metrics that quantify the extent to which the parameters in a model have been updated or adapted. We provide R code that can quickly rank parameter importance and calculate quality metrics using only the results of a standard probabilistic sensitivity analysis.
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