Characterising HIV acquisition risk, treatment gaps and populations reached through venue-based outreach and clinical services in Blantyre, Malawi: findings from a district-wide CLOVE Study.

BACKGROUND: In 2017, Blantyre district had the highest adult HIV prevalence in Malawi (17.7%) and lowest viral suppression (60%). In response, the Ministry of Health expanded prevention and treatment services. We assessed whether outreach to social venues could identify individuals with increased HIV acquisition risk or with unsuppressed HIV not currently reached by clinic-based services. METHODS: We conducted a cross-sectional bio-behavioral survey in Blantyre, Malawi, from January to March 2022. We visited social venues where people meet new sexual partners and government clinics providing HIV testing or STI screening. Participants aged > 15 years were interviewed, and tested for HIV infection if not on ART. HIV recency tests were performed on those testing positive, and dried blood spots (DBS) was collected to quantify viral load and also to identify acute infection in those with HIV- results. RESULTS: HIV prevalence (18.5% vs 8.3%) and unsuppressed HIV infection (3.9% vs 1.7%) were higher among venue-recruited (n=1802) compared with clinic-recruited participants(n=2313). Among PLHIV at both clinics (n=199) and venues (n=289), 79% were virally suppressed. Few had acute(n=1) or recent infection(n=8). Among women, HIV prevalence was four times higher (38.9% venue vs 8.9% clinic). At clinics, PLHIV reporting visiting venues were less likely to be suppressed (54.6 vs 82.6%). More men at venues than at clinics reported paying for sex (49% vs 30%) or having multiple sex partners in the past 4 weeks (32% vs 16%). CONCLUSIONS: Enhanced venue-based prevention and testing for men and women could reduce treatment lapses, HIV treatment outcomes and reduce onward transmission.

AICAR promotes endothelium-independent vasorelaxation by activating AMP-activated protein kinase via increased ZMP and decreased ATP/ADP ratio in aortic smooth muscle.

OBJECTIVES: AICAR, an adenosine analog, has been shown to exhibit vascular protective effects through activation of AMP-activated protein kinase (AMPK). However, it remains unclear as to whether adenosine kinase-mediated ZMP formation or adenosine receptor activation contributes to AICAR-mediated AMPK activation and/or vasorelaxant response in vascular smooth muscle. METHODS AND RESULTS: In the present study using endothelium-denuded rat aortic ring preparations, isometric tension measurements revealed that exposure to 1 mM AICAR for 30 min resulted in inhibition of phenylephrine (1 µM)-induced smooth muscle contractility by ∼35%. Importantly, this vasorelaxant response by AICAR was prevented after pretreatment of aortic rings with an AMPK inhibitor (compound C, 40 µM) and adenosine kinase inhibitor (5-iodotubercidin, 1 µM), but not with an adenosine receptor blocker (8-sulfophenyltheophylline, 100 µM). Immunoblot analysis of respective aortic tissues showed that AMPK activation seen during vasorelaxant response by AICAR was abolished by compound C and 5-iodotubercidin, but not by 8-sulfophenyltheophylline, suggesting ZMP involvement in AMPK activation. Furthermore, LC-MS/MS MRM analysis revealed that exposure of aortic smooth muscle cells to 1 mM AICAR for 30 min enhanced ZMP level to 2014.9 ± 179.4 picomoles/mg protein (vs. control value of 8.5 ± 0.6; p<0.01), which was accompanied by a significant decrease in ATP/ADP ratio (1.08 ± 0.02 vs. 2.08 ± 0.06; p<0.01). CONCLUSIONS: Together, the present findings demonstrate that AICAR-mediated ZMP elevation and the resultant AMPK activation in vascular smooth muscle contribute to vasorelaxation.

Imatinib improves insulin resistance and inhibits injury-induced neointimal hyperplasia in high fat diet-fed mice.

Imatinib, a PDGF receptor tyrosine kinase inhibitor, has been shown to suppress intimal hyperplasia in different animal models under normal metabolic milieu, diabetic, and/or hypercholesterolemic conditions. However, the impact of imatinib treatment on injury-induced neointimal hyperplasia has not yet been investigated in the setting of insulin resistance without frank diabetes. Using a mouse model of high fat diet (HFD)-induced insulin resistance and guidewire-induced arterial injury, the present study demonstrates that intraperitoneal administration of imatinib (25 mg/kg/day) for ~3 weeks resulted in a marked attenuation of neointimal hyperplasia (intima/media ratio) by ~78% (n = 6-9 per group; P < 0.05). Imatinib treatment also led to significant improvements in key metabolic parameters. In particular, imatinib improved insulin resistance and glucose tolerance, as revealed by complete inhibition of HFD-induced increase in HOMA-IR index and AUCIPGTT, respectively. In addition, imatinib treatment led to diminutions in HFD-induced increases in plasma total cholesterol and triglycerides by ~73% and ~59%, respectively. Furthermore, imatinib decreased HFD-induced increase in visceral fat accumulation by ~51% (as determined by epididymal white adipose tissue weight). Importantly, imatinib treatment in HFD-fed mice enhanced plasma levels of high-molecular-weight adiponectin by ~2-fold without affecting total adiponectin. However, there were no significant changes in mean arterial pressure in insulin-resistant state or after imatinib exposure, as measured by tail-cuff method. Together, the present findings suggest that targeting PDGF receptor tyrosine kinase using imatinib may provide a realistic treatment option to prevent injury-induced neointimal hyperplasia and diet-induced insulin resistance in obesity.

Autocrine IL6-Mediated Activation of the STAT3-DNMT Axis Silences the TNFα-RIP1 Necroptosis Pathway to Sustain Survival and Accumulation of Myeloid-Derived Suppressor Cells.

Although accumulation of myeloid-derived suppressor cells (MDSC) is a hallmark of cancer, the underlying mechanism of this accumulation within the tumor microenvironment remains incompletely understood. We report here that TNFα-RIP1-mediated necroptosis regulates accumulation of MDSCs. In tumor-bearing mice, pharmacologic inhibition of DNMT with the DNA methyltransferease inhibitor decitabine (DAC) decreased MDSC accumulation and increased activation of antigen-specific cytotoxic T lymphocytes. DAC-induced decreases in MDSC accumulation correlated with increased expression of the myeloid cell lineage-specific transcription factor IRF8 in MDSCs. However, DAC also suppressed MDSC-like cell accumulation in IRF8-deficient mice, indicating that DNA methylation may regulate MDSC survival through an IRF8-independent mechanism. Instead, DAC decreased MDSC accumulation by increasing cell death via disrupting DNA methylation of RIP1-dependent targets of necroptosis. Genome-wide DNA bisulfite sequencing revealed that the Tnf promoter was hypermethylated in tumor-induced MDSCs in vivo. DAC treatment dramatically increased TNFα levels in MDSC in vitro, and neutralizing TNFα significantly increased MDSC accumulation and tumor growth in tumor-bearing mice in vivo. Recombinant TNFα induced MDSC cell death in a dose- and RIP1-dependent manner. IL6 was abundantly expressed in MDSCs in tumor-bearing mice and patients with human colorectal cancer. In vitro, IL6 treatment of MDSC-like cells activated STAT3, increased expression of DNMT1 and DNMT3b, and enhanced survival. Overall, our findings reveal that MDSCs establish a STAT3-DNMT epigenetic axis, regulated by autocrine IL6, to silence TNFα expression. This results in decreased TNFα-induced and RIP1-dependent necroptosis to sustain survival and accumulation. SIGNIFICANCE: These findings demonstrate that targeting IL6 expression or function represent potentially effective approaches to suppress MDSC survival and accumulation in the tumor microenvironment.

Qualitative impact assessment of an educational workshop on primary care practitioner attitudes to NICE HIV testing guidelines.

BACKGROUND: In 2013, Public Health England piloted the '3Cs (chlamydia, contraception, condoms) and HIV (human immunodeficiency virus)' educational intervention in 460 GP surgeries. The educational HIV workshop aimed to improve the ability and confidence of staff to offer HIV testing in line with national guidelines. AIM: To qualitatively assess the impact of an educational workshop on GP staff's attitudes to NICE HIV testing guidelines. DESIGN & SETTING: Qualitative interviews with GP staff across England before and after an educational HIV workshop. METHOD: Thirty-two GP staff (15 before and 17 after educational HIV workshop) participated in interviews exploring their views and current practice of HIV testing. Interview transcripts were thematically analysed and examined, using the components of the theory of planned behaviour (TPB) and normalisation process theory (NPT) as a framework. RESULTS: GPs reported that the educational HIV workshop resulted in increased knowledge of, and confidence to offer, HIV tests based on indicator conditions. However, overall participants felt they needed additional HIV training around clinical care pathways for offering tests, giving positive HIV results, and current treatments and outcomes. Participants did not see a place for point-of-care testing in general practice. CONCLUSION: Implementation of national HIV guidelines will require multiple educational sessions, especially to implement testing guidelines for indicator conditions in areas of low HIV prevalence. Additional role-play or discussions around scripts suggesting how to offer an HIV test may improve participants' confidence and facilitate increased testing. Healthcare assistants (HCAs) may need specific training to ensure that they are skilled in offering HIV testing within new patient checks.

Application of the COM-B model to barriers and facilitators to chlamydia testing in general practice for young people and primary care practitioners: a systematic review.

BACKGROUND: Chlamydia is a major public health concern, with high economic and social costs. In 2016, there were over 200,000 chlamydia diagnoses made in England. The highest prevalence rates are found among young people. Although annual testing for sexually active young people is recommended, many do not receive testing. General practice is one ideal setting for testing, yet attempts to increase testing in this setting have been disappointing. The Capability, Opportunity, and Motivation Model of Behaviour (COM-B model) may help improve understanding of the underpinnings of chlamydia testing. The aim of this systematic review was to (1) identify barriers and facilitators to chlamydia testing for young people and primary care practitioners in general practice and (2) map facilitators and barriers onto the COM-B model. METHODS: Qualitative, quantitative, and mixed methods studies published after 2000 were included. Seven databases were searched to identify peer-reviewed publications which examined barriers and facilitators to chlamydia testing in general practice. The quality of included studies was assessed using the Critical Appraisal Skills Programme. Data (i.e., participant quotations, theme descriptions, and survey results) regarding study design and key findings were extracted. The data was first analysed using thematic analysis, following this, the resultant factors were mapped onto the COM-B model components. All findings are reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Four hundred eleven papers were identified; 39 met the inclusion criteria. Barriers and facilitators were identified at the patient (e.g., knowledge), provider (e.g., time constraints), and service level (e.g., practice nurses). Factors were categorised into the subcomponents of the model: physical capability (e.g., practice nurse involvement), psychological capability (e.g.: lack of knowledge), reflective motivation (e.g., beliefs regarding perceived risk), automatic motivation (e.g., embarrassment and shame), physical opportunity (e.g., time constraints), social opportunity (e.g., stigma). CONCLUSIONS: This systematic review provides a synthesis of the literature which acknowledges factors across multiple levels and components. The COM-B model provided the framework for understanding the complexity of chlamydia testing behaviour. While we cannot at this juncture state which component represents the most salient influence on chlamydia testing, across all three levels, multiple barriers and facilitators were identified relating psychological capability and physical and social opportunity. Implementation should focus on (1) normalisation, (2) communication, (3) infection-specific information, and (4) mode of testing. In order to increase chlamydia testing in general practice, a multifaceted theory- and evidence-based approach is needed. TRIAL REGISTRATION: PROSPERO CRD42016041786.

Self-sampling kits to increase HIV testing among black Africans in the UK: the HAUS mixed-methods study.

BACKGROUND: Timely diagnosis of human immunodeficiency virus (HIV) enables access to antiretroviral treatment, which reduces mortality, morbidity and further transmission in people living with HIV. In the UK, late diagnosis among black African people persists. Novel methods to enhance HIV testing in this population are needed. OBJECTIVES: To develop a self-sampling kit (SSK) intervention to increase HIV testing among black Africans, using existing community and health-care settings (stage 1) and to assess the feasibility for a Phase III evaluation (stage 2). DESIGN: A two-stage, mixed-methods design. Stage 1 involved a systematic literature review, focus groups and interviews with key stakeholders and black Africans. Data obtained provided the theoretical base for intervention development and operationalisation. Stage 2 was a prospective, non-randomised study of a provider-initiated, HIV SSK distribution intervention targeted at black Africans. The intervention was assessed for cost-effectiveness. A process evaluation explored feasibility, acceptability and fidelity. SETTING: Twelve general practices and three community settings in London. MAIN OUTCOME MEASURE: HIV SSK return rate. RESULTS: Stage 1 - the systematic review revealed support for HIV SSKs, but with scant evidence on their use and clinical effectiveness among black Africans. Although the qualitative findings supported SSK distribution in settings already used by black Africans, concerns were raised about the complexity of the SSK and the acceptability of targeting. These findings were used to develop a theoretically informed intervention. Stage 2 - of the 349 eligible people approached, 125 (35.8%) agreed to participate. Data from 119 were included in the analysis; 54.5% (65/119) of those who took a kit returned a sample; 83.1% of tests returned were HIV negative; and 16.9% were not processed, because of insufficient samples. Process evaluation showed the time pressures of the research process to be a significant barrier to feasibility. Other major barriers were difficulties with the SSK itself and ethnic targeting in general practice settings. The convenience and privacy associated with the SSK were described as beneficial aspects, and those who used the kit mostly found the intervention to be acceptable. Research governance delays prevented implementation in Glasgow. LIMITATIONS: Owing to the study failing to recruit adequate numbers (the intended sample was 1200 participants), we were unable to evaluate the clinical effectiveness of SSKs in increasing HIV testing in black African people. No samples were reactive, so we were unable to assess pathways to confirmatory testing and linkage to care. CONCLUSIONS: Our findings indicate that, although aspects of the intervention were acceptable, ethnic targeting and the SSK itself were problematic, and scale-up of the intervention to a Phase III trial was not feasible. The preliminary economic model suggests that, for the acceptance rate and test return seen in the trial, the SSK is potentially a cost-effective way to identify new infections of HIV. FUTURE WORK: Sexual and public health services are increasingly utilising self-sampling technologies. However, alternative, user-friendly SSKs that meet user and provider preferences and UK regulatory requirements are needed, and additional research is required to understand clinical effectiveness and cost-effectiveness for black African communities. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014010698 and Integrated Research Application System project identification 184223. FUNDING: The National Institute for Health Research Health Technology Assessment programme and the BHA for Equality in Health and Social Care.

Chlamydia and HIV testing, contraception advice, and free condoms offered in general practice: a qualitative interview study of young adults' perceptions of this initiative.

BACKGROUND: Opportunistic chlamydia screening is actively encouraged in English general practices. Based on recent policy changes, Public Health England piloted 3Cs and HIV in 2013-2014, integrating the offer of chlamydia testing with providing condoms, contraceptive information, and HIV testing (referred to as 3Cs and HIV) according to national guidelines. AIM: To determine young adults' opinions of receiving a broader sexual health offer of 3Cs and HIV at their GP practice. DESIGN AND SETTING: Qualitative interviews were conducted in a general practice setting in England between March and June 2013. METHOD: Thirty interviews were conducted with nine male and 21 female patients aged 16-24 years, immediately before or after a routine practice attendance. Data were transcribed verbatim and analysed using a thematic framework. RESULTS: Participants indicated that the method of testing, timing, and the way the staff member approached the topic were important aspects to patients being offered 3Cs and HIV. Participants displayed a clear preference for 3Cs and HIV to be offered at the GP practice over other sexual health service providers. Participants highlighted convenience of the practice, assurance of confidentiality, and that the sexual health discussion was appropriate and routine. Barriers identified for patients were embarrassment, unease, lack of time, religion, and patients believing that certain patients could take offence. Suggested facilitators include raising awareness, reassuring confidentiality, and ensuring the offer is made in a professional and non-judgemental way at the end of the consultation. CONCLUSION: General practice staff should facilitate patients' preferences by ensuring that 3Cs and HIV testing services are made available at their surgery and offered to appropriate patients in a non-judgemental way.

Facilitators and barriers to chlamydia testing in general practice for young people using a theoretical model (COM-B): a systematic review protocol.

INTRODUCTION: Chlamydia is a key health concern with high economic and social costs. There were over 200 000 chlamydia diagnoses made in England in 2015. The burden of chlamydia is greatest among young people where the highest prevalence rates are found. Annual testing for sexually active young people is recommended; however, many of those at risk do not receive testing. General practice has been identified as an ideal setting for testing, yet efforts to increase testing in this setting have not been effective. One theoretical model which may provide insight into the underpinnings of chlamydia testing is the Capability, Opportunity and Motivation Model of Behaviour (COM-B model). The aim of this systematic review is to: (1) identify barriers and facilitators to chlamydia testing for young people in general practice and (2) use a theoretical model to conduct a behavioural analysis of chlamydia testing behaviour. METHODS AND ANALYSIS: Qualitative, quantitative and mixed methods studies published after 2000 will be included. Seven databases (MEDLINE, PubMed, EMBASE, Informit, PsycInfo, Scopus, Web of Science) will be searched to identify peer-reviewed publications which examined barriers and facilitators to chlamydia testing in general practice. Risk of bias will be assessed using the Critical Appraisal Skills Programme. Data regarding study design and key findings will be extracted. The data will be analysed using thematic analysis and the resultant factors will be mapped onto the COM-B model components. All findings will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. ETHICS AND DISSEMINATION: Ethical approval is not required. The results will be disseminated via submission for publication to a peer-review journal when complete and for presentation at national and international conferences. The review findings will be used to inform the development of interventions to facilitate effective and efficient chlamydia testing in general practice.

Service evaluation of an educational intervention to improve sexual health services in primary care implemented using a step-wedge design: analysis of chlamydia testing and diagnosis rate changes.

BACKGROUND: Providing sexual health services in primary care is an essential step towards universal provision. However they are not offered consistently. We conducted a national pilot of an educational intervention to improve staff's skills and confidence to increase chlamydia testing rates and provide condoms with contraceptive information plus HIV testing according to national guidelines, known as 3Cs&HIV. The effectiveness of the pilot on chlamydia testing and diagnosis rates in general practice was evaluated. METHODS: The pilot was implemented using a step-wedge design over three phases during 2013 and 2014 in England. The intervention combined educational workshops with posters, testing performance feedback and continuous support. Chlamydia testing and diagnosis rates in participating general practices during the control and intervention periods were compared adjusting for seasonal trends in chlamydia testing and differences in practice size. Intervention effect modification was assessed for the following general practice characteristics: chlamydia testing rate compared to national median, number of general practice staff employed, payment for chlamydia screening, practice urban/rurality classification, and proximity to sexual health clinics. RESULTS: The 460 participating practices conducted 26,021 tests in the control period and 18,797 tests during the intervention period. Intention-to-treat analysis showed no change in the unadjusted median tests and diagnoses per month per practice after receiving training: 2.7 vs 2.7; 0.1 vs 0.1. Multivariable negative binomial regression analysis found no significant change in overall testing or diagnoses post-intervention (incidence rate ratio (IRR) 1.01, 95 % confidence interval (CI) 0.96-1.07, P = 0.72; 0.98 CI 0.84-1.15, P = 0.84, respectively). Stratified analysis showed testing increased significantly in practices where payments were in place prior to the intervention (IRR 2.12 CI 1.41-3.18, P < 0.001) and in practices with 6-15 staff (6-10 GPs IRR 1.35 (1.07-1.71), P = 0.012; 11-15 GPs IRR 1.37 (1.09-1.73), P = 0.007). CONCLUSION: This national pilot of short educational training sessions found no overall effect on chlamydia testing in primary care. However, in certain sub-groups chlamydia testing rates increased due to the intervention. This demonstrates the importance of piloting and evaluating any service improvement intervention to assess the impact before widespread implementation, and the need for detailed understanding of local services in order to select effective interventions.

Self-Reported Impact of Chlamydia Testing on Subsequent Behavior: Results of an Online Survey of Young Adults in England.

BACKGROUND: The National Chlamydia Screening Programme performs 1.7 million tests annually among young adults in England. The effect of chlamydia screening on subsequent behavior is unknown. This study examined the self-reported impact of testing on young adults' subsequent health care-seeking and sexual behavior. METHODS: We conducted a cross-sectional Web-based anonymous survey using an online panel to recruit 1521 young adults aged 16 to 24 years and resident in England. Survey questions were developed using the theory of planned behavior. Multivariate log-binomial regression was used to identify the variables associated with an impact on subsequent behavior after testing. RESULTS: Most respondents reported that being tested for chlamydia had a positive effect on their subsequent sexual behavior (68.6%; 422/615) or health care-seeking behavior (80.0%; 492/615). In multivariate analysis, being female and having a high level of engagement at last test were both associated with positive impacts on sexual behavior (72.7% [adjusted prevalence ratio {aPR}, 1.19; 95% confidence interval {CI}, 1.07-1.33] and 82.7% [aPR, 1.55; 95% CI, 1.27-1.89], respectively), and health care-seeking behavior (84.4% [aPR, 1.13; 95% Cl, 1.04-1.24] and 86.3% [aPR, 1.23; 95% CI, 1.07-1.41], respectively). Among respondents with minimum level of engagement, 72.4% (76/105) reported an increase in subsequent health care-seeking behavior. CONCLUSIONS: Chlamydia testing had a positive impact on young adults' self-reported health care-seeking and sexual behavior. This suggests that chlamydia screening has a wider effect on young adults' sexual health beyond that of treatment alone.

Intervention to improve care at life's end in inpatient settings: the BEACON trial.

BACKGROUND: Widespread implementation of palliative care treatment plans could reduce suffering in the last days of life by adopting best practices of traditionally home-based hospice care in inpatient settings. OBJECTIVE: To evaluate the effectiveness of a multi-modal intervention strategy to improve processes of end-of-life care in inpatient settings. DESIGN: Implementation trial with an intervention staggered across hospitals using a multiple-baseline, stepped wedge design. PARTICIPANTS: Six Veterans Affairs Medical Centers (VAMCs). INTERVENTION: Staff training was targeted to all hospital providers and focused on identifying actively dying patients and implementing best practices from home-based hospice care, supported with an electronic order set and paper-based educational tools. MAIN MEASURES: Several processes of care were identified as quality endpoints for end-of-life care (last 7 days) and abstracted from electronic medical records of veterans who died before or after intervention (n = 6,066). Primary endpoints were proportion with an order for opioid pain medication at time of death, do-not-resuscitate order, location of death, nasogastric tube, intravenous line infusing, and physical restraints. Secondary endpoints were administration of opioids, order/administration of antipsychotics, benzodiazepines, and scopolamine (for death rattle); sublingual administration; advance directives; palliative care consultations; and pastoral care services. Generalized estimating equations were conducted adjusting for longitudinal trends. KEY RESULTS: Significant intervention effects were observed for orders for opioid pain medication (OR: 1.39), antipsychotic medications (OR: 1.98), benzodiazepines (OR: 1.39), death rattle medications (OR: 2.77), sublingual administration (OR: 4.12), nasogastric tubes (OR: 0.71), and advance directives (OR: 1.47). Intervention effects were not significant for location of death, do-not-resuscitate orders, intravenous lines, or restraints. CONCLUSIONS: This broadly targeted intervention strategy led to modest but statistically significant changes in several processes of care, indicating its potential for widespread dissemination to improve end-of-life care for thousands of patients who die each year in inpatient settings.

Long-term follow-up of moderately hypercholesterolemic hypertensive patients following randomization to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT).

The authors conducted a randomized, controlled, multicenter trial, in which they assigned well-controlled hypertensive participants aged 55 years and older with moderate hypercholesterolemia to receive pravastatin (n=5170) or usual care (n=5185) for 4 to 8 years, when trial therapy was discontinued. Passive surveillance using national databases to ascertain deaths and hospitalizations continued for a total follow-up of 8 to 13 years to assess whether mortality and morbidity differences persisted or new differences developed. During the post-trial period, fatal and nonfatal outcomes were available for 98% and 64% of participants, respectively. The primary outcome was all-cause mortality and the secondary outcomes included cardiovascular mortality, coronary heart disease (CHD), stroke, heart failure, cardiovascular disease, and end-stage renal disease. No significant differences appeared in mortality for pravastatin vs usual care (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.89-1.03) or other secondary outcomes. Similar to the previously reported in-trial result, there was a significant treatment effect for CHD in black patients (HR, 0.79; 95% CI, 0.64-0.98). However, the in-trial result showing a significant treatment by race effect did not remain significant during the entire follow-up (P=.08). These findings are consistent with evidence from other large trials that show statins prevent CHD and add evidence that they are effective for CHD prevention in black patients.

Methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage in residents of Veterans Affairs long-term care facilities: role of antimicrobial exposure and MRSA acquisition.

OBJECTIVE: To identify risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) acquisition in long-term care facility (LTCF) residents. DESIGN: Multicenter, prospective cohort followed over 6 months. SETTING: Three Veterans Affairs (VA) LTCFs. PARTICIPANTS: All current and new residents except those with short stay (<2 weeks). METHODS: MRSA carriage was assessed by serial nares cultures and classified into 3 groups: persistent (all cultures positive), intermittent (at least 1 but not all cultures positive), and noncarrier (no cultures positive). MRSA acquisition was defined by an initial negative culture followed by more than 2 positive cultures with no subsequent negative cultures. Epidemiologic data were collected to identify risk factors, and MRSA isolates were typed by pulsed-field gel electrophoresis (PFGE). RESULTS: Among 412 residents at 3 LTCFs, overall MRSA prevalence was 58%, with similar distributions of carriage at all 3 facilities: 20% persistent, 39% intermittent, 41% noncarriers. Of 254 residents with an initial negative swab, 25 (10%) acquired MRSA over the 6 months; rates were similar at all 3 LTCFs, with no clusters evident. Multivariable analysis demonstrated that receipt of systemic antimicrobials during the study was the only significant risk factor for MRSA acquisition (odds ratio, 7.8 [95% confidence interval, 2.1-28.6]; P = .002). MRSA strains from acquisitions were related by PFGE to those from a roommate in 9/25 (36%) cases; 6 of these 9 roommate sources were persistent carriers. CONCLUSIONS: MRSA colonization prevalence was high at 3 separate VA LTCFs. MRSA acquisition was strongly associated with antimicrobial exposure. Roommate sources were often persistent carriers, but transmission from roommates accounted for only approximately one-third of MRSA acquisitions.

Characteristics and lipid distribution of a large, high-risk, hypertensive population: the lipid-lowering component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) consisted of 42,418 participants randomized to one of four antihypertensive treatment groups: chlorthalidone, amlodipine, lisinopril, or doxazosin. A subset of these participants with fasting low-density lipoprotein cholesterol levels 100-189 mg/dL were randomized into a lipid-lowering component: 5170 to receive pravastatin (40 mg daily) and 5185 to receive usual care. This report describes the characteristics and lipid distribution of these participants. There were no important differences between the randomized treatment groups. Women had higher total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol than men. There was a similar finding for black participants compared with whites, except blacks had lower triglycerides. Diabetics had lower high-density lipoprotein cholesterol and higher triglycerides than nondiabetics, and patients with body mass index <25 kg/m(2) had higher high-density lipoprotein cholesterol but lower low-density lipoprotein cholesterol and triglycerides than patients with higher body mass index. The success of the randomization of this large, diverse population and the differences in the lipid distributions among its subgroups will allow further understanding of optimal lipid-lowering treatment.