Cheryl Denski

Task-shifting of antiretroviral delivery from health care workers to persons living with HIV/AIDS: clinical outcomes of a community-based program in Kenya.

Objectives:To assess whether community-based care delivered by people living with HIV/AIDS (PLWAs) could replace clinic-based HIV care. Design:Prospective cluster randomized controlled clinical trial. Setting:Villages surrounding 1 rural clinic in western Kenya. Subjects:HIV-infected adults clinically stable on antiretroviral therapy (ART). Intervention:The intervention group received monthly Personal Digital Assistant supported home assessments by PLWAs with clinic appointments every 3 months. The control group received standard of care monthly clinic visits. Main Outcomes Measured:Viral load, CD4 count, Karnofsky score, stability of ART regimen, opportunistic infections, pregnancies, and number of clinic visits. Results:After 1 year, there were no significant intervention-control differences with regard to detectable viral load, mean CD4 count, decline in Karnofsky score, change in ART regimen, new opportunistic infection, or pregnancy rate. Intervention patients made half as many clinic visits as did controls (P < 0.001). Conclusions:Community-based care by PLWAs resulted in similar clinical outcomes as usual care but with half the number of clinic visits. This pilot study suggests that task-shifting and mobile technologies can deliver safe and effective community-based care to PLWAs, expediting ART rollout and increasing access to treatment while expanding the capacity of health care institutions in resource-constrained environments.

Effect of Covered Metallic Stents Compared With Plastic Stents on Benign Biliary Stricture Resolution: A Randomized Clinical Trial

IMPORTANCE Endoscopic placement of multiple plastic stents in parallel is the first-line treatment for most benign biliary strictures; it is possible that fully covered, self-expandable metallic stents (cSEMS) may require fewer endoscopic retrograde cholangiopancreatography procedures (ERCPs) to achieve resolution. OBJECTIVE To assess whether use of cSEMS is noninferior to plastic stents with respect to stricture resolution. DESIGN, SETTING, AND PARTICIPANTS Multicenter (8 endoscopic referral centers), open-label, parallel, randomized clinical trial involving patients with treatment-naive, benign biliary strictures (N = 112) due to orthotopic liver transplant (n = 73), chronic pancreatitis (n = 35), or postoperative injury (n = 4), who were enrolled between April 2011 and September 2014 (with follow-up ending October 2015). Patients with a bile duct diameter less than 6 mm and those with an intact gallbladder in whom the cystic duct would be overlapped by a cSEMS were excluded. INTERVENTIONS Patients (N = 112) were randomized to receive multiple plastic stents or a single cSEMS, stratified by stricture etiology and with endoscopic reassessment for resolution every 3 months (plastic stents) or every 6 months (cSEMS). Patients were followed up for 12 months after stricture resolution to assess for recurrence. MAIN OUTCOMES AND MEASURES Primary outcome was stricture resolution after no more than 12 months of endoscopic therapy. The sample size was estimated based on the noninferiority of cSEMS to plastic stents, with a noninferiority margin of -15%. RESULTS There were 55 patients in the plastic stent group (mean [SD] age, 57 [11] years; 17 women [31%]) and 57 patients in the cSEMS group (mean [SD] age, 55 [10] years; 19 women [33%]). Compared with plastic stents (41/48, 85.4%), the cSEMS resolution rate was 50 of 54 patients (92.6%), with a rate difference of 7.2% (1-sided 95% CI, -3.0% to ∞; P < .001). Given the prespecified noninferiority margin of -15%, the null hypothesis that cSEMS is less effective than plastic stents was rejected. The mean number of ERCPs to achieve resolution was lower for cSEMS (2.14) vs plastic (3.24; mean difference, 1.10; 95% CI, 0.74 to 1.46; P < .001). CONCLUSIONS AND RELEVANCE Among patients with benign biliary strictures and a bile duct diameter 6 mm or more in whom the covered metallic stent would not overlap the cystic duct, cSEMS were not inferior to multiple plastic stents after 12 months in achieving stricture resolution. Metallic stents should be considered an appropriate option in patients such as these. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01221311.

Inverse relationship between long-chain n-3 fatty acids and risk of sudden cardiac death in patients starting hemodialysis

Experimental and clinical evidence suggests that long chain n-3 fatty acids may protect against sudden cardiac death, the leading cause of mortality in hemodialysis patients. Here we investigated whether long chain n-3 fatty acids have a protective relationship with sudden cardiac death in 100 patients who died of sudden cardiac death during the first year of starting hemodialysis and 300 patients who survived. Individuals were selected from a nationally representative cohort of over 1000 U.S. hemodialysis units in 2004–2005. The odds of sudden cardiac death were calculated by quartile of long chain n-3 fatty acids levels over the first year. There was a significant inverse relationship between long chain n-3 fatty acids and the risk of sudden cardiac death even after adjusting for relevant co-morbid conditions, biochemical values, and dietary fats. The odds of sudden cardiac death at 1 year for the second, third, and fourth quartile groups of long chain n-3 fatty acids were 0.37, 0.22, and 0.20, respectively, compared to the lowest quartile. This significant inverse relationship was maintained even during the highest-risk first few months on hemodialysis. Thus, long chain n-3 fatty acids are strongly and independently associated with a lower risk of sudden cardiac death in hemodialysis patients throughout the first year of hemodialysis.

Low blood levels of long-chain n-3 polyunsaturated fatty acids in US hemodialysis patients: Clinical implications

Background: Cardioprotective and other clinical benefits of long-chain n–3 polyunsaturated fatty acids (PUFA) are inversely related to dietary intake and hence blood content. We therefore investigated, in the first study of its kind, the blood content and distribution of these fatty acids in a large representative population of US hemodialysis patients. Methods: Frozen sera were obtained from 400 individuals who were part of a large, contemporary, representative cohort of US incident hemodialysis patients. Long-chain n–3 PUFA were measured in total serum lipids and in the neutral and polar serum fractions using gas chromatography and solid phase extraction techniques. Mean long-chain n–3 PUFA levels were compared to levels in other dialysis and nondialysis populations from published reports. Results: The study population was qualitatively similar to the overall US hemodialysis population in terms of major clinical characteristics. Long-chain n–3 PUFA were present in the serum polar fraction, with essentially none being detected in the neutral fraction (p < 0.0001 for polar vs. neutral fractions for all three long-chain n–3 PUFA). Mean serum long-chain n–3 PUFA levels (weight percent (±SD): total 1.55 ± 0.95, polar 3.99 ± 1.45) were low compared to nondialysis and most other non-US hemodialysis cohorts. Conclusions: While US hemodialysis patients have a blood distribution of long-chain n–3 PUFA that is similar to that in the general population, blood content is among the lowest recorded in the medical literature. This has implications for renal dietary recommendations and makes US patients an ideal group for testing the clinical effects of long-chain n–3 PUFA supplementation.

Association of Chlamydia trachomatis Infection With Redetection of Human Papillomavirus After Apparent Clearance

BACKGROUND Persistent infection with oncogenic human papillomavirus (HPV) is associated with an increased risk of cervical malignancy. Redetection of type-specific HPV after a period of nondetection may be caused by reactivation of a low-level persistent infection. Little is known about factors associated with type-specific HPV redetection. METHODS For a longitudinal cohort of adolescent women with frequent behavioral and sexually transmitted infection (STI) information (every 3 months), Cox proportional hazard models were used to assess the influence of sexual behaviors and STIs on the redetection of oncogenic or high-risk HPV infections. RESULTS A total of 210 type-specific high-risk HPV detection episode periods were identified in this longitudinal cohort; 71 (33.8%) were characterized by a period of nondetection followed by redetection. Chlamydia trachomatis (hazard ratio [HR], 3.14; 95% confidence interval [CI], 1.44-6.86) was associated with redetection; redetection was >2 times more likely with each additional self-reported sex partner in the past 3 months (HR, 2.26; 95% CI, 1.35-3.78). CONCLUSIONS This study demonstrates the role of C. trachomatis and number of recent sexual partners in type-specific HPV redetection. Given that persistent oncogenic HPV infections are associated with cancer-related outcomes, understanding the potential role of such factors in the pathogenesis of HPV-related outcomes is important.

Natural History of Multiple Human Papillomavirus Infections in Female Adolescents With Prolonged Follow-up

PURPOSE The aim of the study was to better characterize the natural history of human papillomavirus (HPV) infections in female adolescents. METHODS Female adolescents were enrolled in a longitudinal study. Self-vaginal samples were obtained every 3 months and tested for HPV. No participants received HPV vaccination. The findings for 40 female adolescents with the longest follow-up are reported in this study. RESULTS Average age at the time of enrollment was 15.2 years (range: 14-17; SD: .97). Mean duration of follow-up was 6.7 years (range: 4.4-9.2; SD: 1.2). In all, 32 participants (80%) reported being involved in sexual activity before their enrollment in the study; all reported being involved in sexual activity before enrollment; all reported being involved in sexual activity during follow-up. Baseline and cumulative prevalence of HPV among participants was 55% and 100%, respectively. During the study, each participant tested positive for a mean of 14 HPV types. Cumulatively, HPV 16 was detected in 29 of 40 participants (72.5%). Mean duration of high- and low-risk infections was 655.9 (median: 433) and 524.1 days (median: 334), respectively. CONCLUSION With prolonged follow-up, HPV infections with multiple types were found in all participants. Most had infection with HPV-16 or HPV-18, the oncogenic types represented in current vaccines, as well as infection with other oncogenic types. These data reinforce the importance of vaccine and non-vaccine strategies for prevention of HPV infections.

Low-level persistence of human papillomavirus 16 DNA in a cohort of closely followed adolescent women†

Most human papillomavirus (HPV) infections in young women become undetectable by standard assays after a few months. It is possible that many HPV infections do not actually clear, but persist at very low levels for years, becoming detected again later in life. The purpose of this study is to describe HPV 16 clearance, reappearance, and low‐level persistence in a cohort of adolescent women. Adolescent women (N = 66), not vaccinated against HPV, were recruited from 1998 to 2008 into a longitudinal study. Self‐collected vaginal samples were obtained quarterly and tested for HPV by Linear Array HPV Genotyping Test (LA‐HPV). To explore low‐level persistence, a type‐specific nested PCR for HPV 16 (TSN‐PCR‐16) was developed. Women with HPV 16 detected by LA‐HPV had their negative swabs retested with TSN‐PCR‐16. Forty‐two participants with HPV 16, followed for a mean of 6.3 years, were analyzed. Using LA‐HPV, the median duration of HPV 16 detection was 428 days (SD 852.5 days). TSN‐PCR‐16 detected HPV 16 during periods of LA‐HPV non‐detection in samples from many women. Using a combination of LA‐HPV and TSN‐PCR‐16 results, the median duration of HPV 16 detection was 1,022.5 days (SD 943.7 days). The durations of detection differed significantly between the two methods (P = 0.0042) with a mean difference of 434.5 days. In adolescent females, duration of HPV 16 detection was significantly longer when TSN‐PCR‐16 was combined with LA‐HPV. Some apparently cleared HPV 16 could be shown to persist at low levels using nested PCR. J. Med. Virol. 83:1362–1369, 2011.

FATTY ACIDS AND OTHER RISK FACTORS FOR SUDDEN CARDIAC DEATH IN PATIENTS STARTING HEMODIALYSIS

Background: Little is known about risk factors for sudden cardiac death in hemodialysis patients during the high-risk first year of dialysis. We therefore undertook to identify such risk factors in a nationally representative cohort and were able to include baseline levels of blood fatty acids, some of which influence arrhythmogenicity and sudden cardiac death risk. Design: The study cohort included 100 patients who died of sudden cardiac death during the first year of hemodialysis and 300 frequency-matched controls. Using the elastic net statistical method, numerous demographic and clinical characteristics were included with baseline total serum levels for 11 major fatty acids (model 1) and with serum phospholipid fractions of these same fatty acids (model 2). Final models included only covariates that had a non-zero coefficient. Results: In model 1, serum albumin [odds ratio (95% CI): 0.55 (0.33-0.93); p = 0.03] and total serum long-chain n-3 docosapentaenoic acid [0.70 (0.51-0.97); p = 0.03] were inversely associated with the odds of sudden cardiac death, while the total serum saturated fatty acid level had a direct association [1.01 (1.00-1.02); p = 0.03]. In model 2, serum albumin and docosapentaenoic acid remained inversely associated with sudden cardiac death in a similar manner as in model 1. Pulse pressure also had an inverse association [0.96 (0.93-1.00); p < 0.05]. Conclusions: Several factors, including blood content of docosapentaenoic acid and saturated fatty acids, were associated with the odds of sudden cardiac death during year one of hemodialysis. These results raise the possibility that dietary modification may reduce sudden death risk.

DNA detection and seroprevalence of human papillomavirus in a cohort of adolescent women.

Objectives Human papillomavirus (HPV) infections are common in adolescent women, while the rare cancerous sequelae of HPV infections do not generally occur until the 4th or 5th decades of life. This prospective study of a cohort of adolescent women was performed to further our knowledge of the natural history of incident and prevalent HPV infections. Methods Self-vaginal swabs collected from high-risk, unvaccinated adolescent women in a longitudinal study were analysed for HPV DNA. Sera were collected at enrolment and later tested for HPV antibodies. Statistical analysis was performed to determine the HPV genotype distribution and duration of detection, and to determine rates of seropositivity and seroconversion for HPV types represented in the assays. Results 146 subjects (mean enrolment age=15.4 years; mean duration of follow-up=5.8 years) had samples adequate for analysis of HPV detection, and 95 of these subjects had paired sera available. The cumulative prevalence for high-risk and low-risk HPV types was 95.9% and 91.1%, respectively. HPV types 6, 11, 16 and 18 (HPV types represented in the quadrivalent vaccine) were found at some point in 40.4%, 6.2%, 48% and 24% of participants, respectively. Serological data confirmed exposure to these vaccine-covered types, as well as to other high-risk HPV types. Conclusions In this cohort of adolescent women, high- and low-risk HPV types were frequently detected, and serological data confirmed exposure in most subjects. The high-prevalence HPV types represented in the quadrivalent HPV vaccine further support vaccination of women at an age well before sexual debut.