Optimizing Pre-Exposure Antiretroviral Prophylaxis Adherence in Men Who Have Sex with Men: Results of a Pilot Randomized Controlled Trial of “Life-Steps for PrEP”

Antiretroviral pre-exposure prophylaxis (PrEP) has been demonstrated to decrease HIV acquisition in multiple efficacy trials, but medication adherence is critical, and was suboptimal in several studies. Fifty HIV-uninfected at risk men who have sex with men (MSM) were randomized to a cognitive behavioral intervention condition or a time and session-matched comparison counseling intervention. The experimental intervention entailed four nurse-delivered initial and two booster sessions based on Life-Steps, an ART treatment adherence intervention. The comparison condition provided information and supportive counseling. The primary analyses compared adherence (Wisepill and tenofovir plasma levels) at 3 and 6 months. Fifty-eight MSM were screened to enroll 50 participants. Median age was 38.2 years old, 86% were white; 64% had completed college. Wisepill adherence was high in both groups, and not statistically different. Plasma tenofovir levels were significantly higher in the intervention group at 6 months using mean substitution analysis (i.e., computing missing variables) (p = 0.037), however, in the completer analyses (i.e., using only those completing all study visits), there were no statistically significant differences between randomization conditions. Medication adherence was high across a cognitive-behavioral (Life-Steps) and time-matched counseling intervention for PrEP adherence, with some evidence suggesting superiority of Life-Steps in this pilot RCT. Further evaluation in a fully powered efficacy trial is warranted to assess the robustness of this intervention.     

Recent Trends in the Prevalence of Crohn’s Disease and Ulcerative Colitis in a Commercially Insured US Population

Purpose

Most US inflammatory bowel disease (IBD) epidemiology studies conducted to date have sampled small, geographically restricted populations and have not examined time trends. The aim of our study was to determine the prevalence of Crohn’s disease (CD) and ulcerative colitis (UC) in a commercially insured US population and compare prevalences across sociodemographic characteristics and time.

Methods

Using claims data from approximately 12 million Americans, we performed three consecutive 2-year cross-sectional studies. Cases of CD and UC were identified using a previously described algorithm. Prevalence was estimated by dividing cases by individuals in the source population. Logistic regression was used to compare prevalences by region, age, and sex.

Results

In 2009, the prevalences of CD and UC in children were 58 [95 % confidence interval (CI) 55–60] and 34 (95 % CI 32–36), respectively. In adults, the respective prevalences were 241 (95 % CI 238–245) and 263 (95 % CI 260–266). Data analysis revealed that IBD prevalences have slightly increased over time. Based on census data, an estimated 1,171,000 Americans have IBD (565,000 CD and 593,000 UC).

Conclusions

Analysis of the epidemiological data revealed an increasing burden of IBD in recent years, which may be used to inform policy.     

Should Older People in Residential Care Receive Vitamin D to Prevent Falls? Results of a Randomized Trial

OBJECTIVES: To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient. DESIGN: Randomized, placebo-controlled double-blind, trial of 2 years' duration. SETTING: Multicenter study in 60 hostels (assisted living facilities) and 89 nursing homes across Australia. PARTICIPANTS: Six hundred twenty-five residents (mean age 83.4) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L. INTERVENTION: Vitamin D supplementation (ergocalciferol, initially 10,000 IU given once weekly and then 1,000 IU daily) or placebo for 2 years. All subjects received 600 mg of elemental calcium daily as calcium carbonate. MEASUREMENTS: Falls and fractures recorded prospectively in study diaries by care staff. RESULTS: The vitamin D and placebo groups had similar baseline characteristics. In intention-to-treat analysis, the incident rate ratio for falling was 0.73 (95% confidence interval (CI)=0.57-0.95). The odds ratio for ever falling was 0.82 (95% CI=0.59-1.12) and for ever fracturing was 0.69 (95% CI=0.40-1.18). An a priori subgroup analysis of subjects who took at least half the prescribed capsules (n=540), demonstrated an incident rate ratio for falls of 0.63 (95% CI=0.48-0.82), an odds ratio (OR) for ever falling of 0.70 (95% CI=0.50-0.99), and an OR for ever fracturing of 0.68 (95% CI=0.38-1.22). CONCLUSION: Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient.     

Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn’s Disease

Digestive Diseases and Sciences - Increased mucosa-associated E. coli are present in Crohn’s disease, but their role in pathogenesis is uncertain. To assess efficacy and safety of an...     

Comparative Effects of Different Doses of Ribavirin Plus Interferon-α2b for Therapy of Chronic Hepatitis C: Results of a Controlled, Randomized Trial

Compared to either drug alone, therapy with the combination of ribavirin and interferon- leads to improved rates of response in patients with chronic hepatitis C. Side effects often mandate downward dose adjustment or cessation of therapy, and the optimal dose of ribavirin has not been established. The aim of this study was to learn whether 600 mg ribavirin per day would prove as efficacious as 1000–1200 mg/day when combined with interferon (3 million units thrice weekly) for therapy of patients previously treated with standard interferon who had failed to respond or who had relapsed. We enrolled 69 patients with chronic hepatitis C and compensated liver disease: 45 were men, 65 were Caucasian, 48 were infected with genotype 1 hepatitis C virus. By random assignment, 35 received 600 mg ribavirin/day (group A), whereas the other 34 received 1000 mg (75 kg body wt) or 1200 mg/day (>75 kg body wt) (group B). At baseline, the two groups were well matched for demographic and laboratory features. In both groups, mean serum levels of alanine aminotransferase (ALT) and hepatitis C viral (HCV) RNA levels fell promptly and remained significantly lower than baseline throughout 24 weeks of therapy. There was no significant difference in mean levels of ALT or HCV RNA during therapy or at the end of follow-up (24 weeks after cessation of therapy). At the end of 24 weeks of posttherapy follow-up, 12 patients in each group had undetectable HCV RNA in serum, whereas 11 (31%) in group A and 9 (26.5%) in group B had normal serum ALT levels. The lower doses of ribavirin (group A) were tolerated better. %In conclusion, in previous nonresponders or relapsers to interferon done, combination therapy with interferon-_2b (3 MU thrice weekly) + 600 mg ribavirin/day is tolerated better and is as effective as interferon plus higher (standard) doses of ribavirin (1000–1200 mg/day).     

Do Gerontology Nurse Specialists Make a Difference in Hospitalization of Long‐Term Care Residents? Results of a Randomized Comparison Trial

Residents of long‐term care facilities have highly complex care needs and quality of care is of international concern. Maintaining resident wellness through proactive assessment and early intervention is key to decreasing the need for acute hospitalization. The Residential Aged Care Integration Program (RACIP) is a quality improvement intervention to support residential aged care staff and includes on‐site support, education, clinical coaching, and care coordination provided by gerontology nurse specialists (GNSs) employed by a large district health board. The effect of the outreach program was evaluated through a randomized comparison of hospitalization 1 year before and after program implementation. The sample included 29 intervention facilities (1,425 residents) and 25 comparison facilities (1,128 residents) receiving usual care. Acute hospitalization rate unexpectedly increased for both groups after program implementation, although the rate of increase was significantly less for the intervention facilities. The hospitalization rate after the intervention increased 59% for the comparison group and 16% for the intervention group (rate ratio (RR) = 0.73, 95% confidence interval (CI) = 0.61–0.86, P < .001). Subgroup analysis showed a significantly lower rate change for those admitted for medical reasons for the intervention group (13% increase) than the comparison group (69% increase) (RR = 0.67, 95% CI = 0.56–0.82, P < .001). Conversely, there was no significant difference in the RR for surgical admissions between the intervention and comparison groups (RR = 1.0, 95% CI = 0.68–1.46, P = .99). The integration of GNS expertise through the RACIP intervention may be one approach to support staff to provide optimal care and potentially improve resident health.     

Evaluation of the Use of BioGlue® in the Treatment of High Anal Fistulas: Preliminary Results of a Pilot Study

Purpose Treatment of anal fistulas by use of adhesives is an attractive method because of its simplicity and it can be performed on an ambulatory basis. Furthermore, if the treatment is unsuccessful, adhesive use does not subsequently prevent the surgeon from utilizing alternative surgical techniques and/or products. BioGlue? Surgical Adhesive is a two-component surgical adhesive composed of bovine serum albumin and glutaraldehyde. We evaluated the usefulness of BioGlue? for the treatment of high transsphincter anal fistulas. Methods Patients diagnosed with high transsphincter anal fistulas of cryptoglandular origin, whether relapsed or not, were included in this study. A seton was placed before the injection of BioGlue? into the fistula track of high transsphincter anal fistulas in patients with secondary tracts and/or purulent collections. Clinical charts, operative reports, and endoanal echography results obtained for each patient were reviewed. Results Fourteen patients (13 males; mean age, 39.9 (range, 24–66) years) with high transsphincter anal fistulas of cryptoglandular origin were recruited into the study. The average time of symptom evolution was 35.6 (range, 2–96) months. Ten of 14 cases were for relapsed fistulas. Six patients required the placement of a seton 37 (range, 32–42) days before the BioGlue? injection. Patients were followed for a mean length of 13.92 (range, 3–21) months, and the fistula healed completely in only seven patients (50 percent). Conclusions These preliminary results demonstrate that BioGlue? may be useful for treating patients with high transsphincter anal fistulas. Further prospective long-term studies are needed.     

Increased Frequency of Mutations in the Gene Responsible for Familial Mediterranean Fever (MEFV) in a Cohort of Patients with Ulcerative Colitis: Evidence for a Potential Disease-Modifying Effect?

The MEFV gene, responsible for familial Mediterranean fever (FMF), is involved in inflammatory reactions through altered leukocyte apoptosis, secretion of interleukin (IL)-1β, and activation of the NF-κ B pathway. Ulcerative Colitis (UC) and FMF are both characterized by a recurrent pattern of presentation with periods of remission and flares associated with neutrophilic infiltration at the site of injury. The aim of this study was to investigate the possible correlation between UC and MEFV gene alterations. Twenty-five consecutive, first-diagnosed and untreated UC patients, 28 control patients with rheumatoid arthritis, and 65 normal individuals were analyzed. Nonisotopic RNase Cleavage Assay (NIRCA) was applied as a first-step mutational screening method of exons 10 and 2 of MEFV gene; direct sequencing was subsequently performed to confirm the results. MEFVmutations were identified in 7 (3 M694V/0, 2 M680I/0, 1 E148Q/E148Q, and 1 A744S/0) out of 25 UC patients versus 1 (M694V/0) out of 28 rheumatoid arthritis patients (P = .0199) and 1 (M694V/0) out of 65 healthy controls (P = .0004). Four out of 7 patients with MEFVmutations had inflammatory arthritis, a clinical finding that was not observed in the 18 UC patients with unmutated MEFV (P = .0028). Patients with UC almost universally carried the T A C G MEFV exon 2 haplotype in contrast with normal individuals (P < .0001) and FMF patients (P = .0310). In conclusion the increased frequency of mutations of MEFV in UC patients, especially in those with episodic arthritis, suggests a possible modifying effect of MEFV in the disease process and its localization within the joint. The difference in distribution of MEFV exon 2 haplotypes between UC patients and both FMF patients and normal individuals, suggests that UC patients constitute a genetically distinct population. Larger, longitudinal studies are needed to confirm these initial findings.     

Long-Term Results of the Anterior Delorme’s Operation in the Management of Symptomatic Rectocele

PURPOSE Although the results of surgery for symptomatic rectocele seem satisfactory initially, there is a trend toward deterioration with time. This study was designed to assess the long-term outcome of Anterior Delormes operation for rectocele.METHODS Questionnaires were sent to all females who had Anterior Delormes operation performed in Auckland between 1990 and 2000. The questionnaires included obstructed defecation symptoms and a validated fecal incontinence severity index questionnaire and fecal incontinence quality of life questionnaire. Preoperative and postoperative obstructed defecation symptoms and incontinence score were compared.RESULTS A total of 150 females (mean age, 56 (range, 30–83) years) who had an Anterior Delormes operation for a rectocele were identified. One hundred seven patients (71.5 percent; mean age, 56 years) completed the questionnaire. Median follow-up was four (range, 2–11) years. The number of patients with obstructed defecation reduced from 87 preoperatively to 23 postoperatively using Rome II criteria (P < 0.0001). Postoperatively there was a reduction in the number of patients with each of the symptoms of obstructed defecation from 83 to 27 for straining, 87 to 33 for incomplete emptying, 64 to 14 for feeling of blockage, 41 to 10 for digitation (P < 0.0001 for all). The median incontinence score reduced from 20 of 61 preoperatively to 12 of 61 postoperatively (P = 0.0001).CONCLUSIONS In patients with symptomatic rectocele, Anterior Delormes operation provides long-term benefit for patients with obstructed defecation and leads to a significant improvement of incontinence scores.Presented at the scientific meeting of the Surgical Society of New Zealand, Wellington, New Zealand, September 17, 2003.     

Is Bachmann's Bundle the Only Right Site for Single-Site Pacing to Prevent Atrial Fibrillation? Results of a Multicenter Randomized Trial

The site of atrial pacing influences atrial activation patterns. It is believed that disparities in atrial activation and repolarization are contributors to the development and recurrence of atrial arrhythmias. We hypothesized that pacing from Bachmann's Bundle would improve clinical outcomes in patients with paroxysmal atrial fibrillation compared to right atrial appendage pacing. Pacing from Bachmann's Bundle results in a significant reduction in P wave duration and improvement in biatrial activation symmetry compared to right atrial appendage pacing. Compared to right atrial appendage pacing, Bachmann's bundle pacing improves sinus rhythm (75% vs. 47% at two years, p < 0.01) in patients with a history of paroxysmal atrial fibrillation. Recent studies have confirmed the benefits of Bachmann's Bundle pacing on atrial activation and rhythm regulation. Thus, Bachman's Bundle should be considered the preferred site for atrial pacing in patients with a history of paroxysmal atrial fibrillation.     

Increased Risk of Both Ulcerative Colitis and Crohn’s Disease in a Population Suffering from COPD

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways. In the majority of cases, the inflammation is triggered by tobacco smoke. Smoking also affects the pathogenesis of inflammatory bowel disease (IBD), protecting against ulcerative colitis (UC) and promoting development of Crohn's disease (CD). The present study was undertaken to investigate occurrence of IBD among COPD patients, indicating common inflammatory pathways and shared vulnerability on a genetic basis. The study was designed as a population-based cohort study. All individuals discharged with a diagnosis of COPD from 1987 to 2002 were identified in the Swedish Inpatient Register (n=180,239). Controls and first-degree relatives of both cases and controls were identified using the Multi-Generation Register. Finally, all individuals (n=1,174,557) were compared with the Inpatient Register, identifying discharges with a diagnosis of UC or CD. Hazard ratios (HR) for IBD were determined by Cox proportional hazards regression analysis. COPD patients had a significantly higher risk of both UC (HR 1.83; 95% CI 1.61-2.09) and CD (HR 2.72; 95% CI 2.33-3.18). Among first-degree relatives of COPD patients, there was also an overall increased risk of CD (HR 1.25; 95% CI 1.09-1.43) but not of UC (HR 1.09; 95% CI 0.96-1.23). The kinship of first-degree relatives displayed an increased risk of both UC and CD among siblings (HR 1.49; 95% CI 1.15-1.91 and HR 1.46; 95% CI 1.12-1.89, respectively). The results suggest that COPD and IBD may have inflammatory pathways in common, including genetic variants of genes predisposing for disease.     

Sustaining the Control of Schistosoma mansoni in Western C?te d'Ivoire: Baseline Findings before the Implementation of a Randomized Trial

We report baseline findings before the implementation of a 4-year intervention trial designed to assess the impact of three different school-based treatment schedules with praziquantel to sustain the control of intestinal schistosomiasis. The baseline survey was conducted in 75 schools of western Côte d''Ivoire previously identified with moderate Schistosoma mansoni endemicity (prevalence: 10–24% in children aged 13–14 years). Three stool samples collected over consecutive days were subjected to duplicate Kato-Katz thick smears each. A questionnaire was administered to collect village-specific information that is relevant for schistosomiasis transmission. Overall, 4,953 first graders (aged 5–8 years) and 7,011 school children (aged 9–12 years) had complete parasitologic data. The overall prevalence of S. mansoni was 5.4% among first graders and 22.1% in 9- to 12-year-old children. Open defecation was practiced in all villages. The current baseline findings will be important to better understand the dynamics of S. mansoni prevalence and intensity over the course of this trial that might be governed by village characteristics and specific treatment interventions.