Publications

AIMS

Right ventricular pacing for left ventricular outflow tract gradient reduction in hypertrophic obstructive cardiomyopathy remains controversial. We undertook a meta-analysis for echocardiographic and functional outcomes.

METHODS AND RESULTS

Thirty-four studies comprising 1135 patients met eligibility criteria. In the four blinded randomized controlled trials (RCTs), pacing reduced gradient by 35% [95% confidence interval (CI) 23.2-46.9, P < 0.0001], but there was only a trend towards improved New York Heart Association (NYHA) class [odds ratio (OR) 1.82, CI 0.96-3.44; P = 0.066]. The unblinded observational studies reported a 54.3% (CI 44.1-64.6, P < 0.0001) reduction in gradient, which was a 18.6% greater reduction than the RCTs (P = 0.0351 for difference between study designs). Observational studies reported an effect on unblinded NYHA class at an OR of 8.39 (CI 4.39-16.04, P < 0.0001), 450% larger than the OR in RCTs (P = 0.0042 for difference between study designs). Across all studies, the gradient progressively decreased at longer follow durations, by 5.2% per month (CI 2.5-7.9, P = 0.0001).

CONCLUSION

Right ventricular pacing reduces gradient in blinded RCTs. There is a non-significant trend to reduction in NYHA class. The bias in assessment of NYHA class in observational studies appears to be more than twice as large as any genuine treatment effect.

BACKGROUND

Multiple antiretroviral (ARV) regimens are effective at achieving HIV viral suppression, but differ in pill burden, side effects, barriers to resistance, and impact on comorbidities. Current guidelines advocate for an individualized approach to ARV regimen selection, but synthesizing these modifying factors is complex and time-consuming.

METHODS

We describe the development of HIV-ASSIST (https://www.hivassist.com), a free, online decision support tool for ARV selection and HIV education. HIV-ASSIST ranks potential ARV options for any given patient scenario using a composite objective of achieving viral suppression while maximizing tolerability and adherence. We used a multiple-criteria decision analysis framework to construct mathematical algorithms and synthesize various patient-specific (eg, comorbidities and treatment history) and virus-specific (eg, HIV mutations) attributes. We then conducted a validation study to evaluate HIV-ASSIST with prescribing practices of experienced HIV providers at 4 large academic centers. We report on concordance of provider ARV selections with the 5 top-ranked HIV-ASSIST regimens for 10 diverse hypothetical patient-case scenarios.

RESULTS

In the validation cohort of 17 experienced HIV providers, we found 99% concordance between HIV-ASSIST recommendations and provider ARV selections for 4 case-scenarios of ARV-naive patients. Among 6 cases of ARV-experienced patients (3 with and 3 without viremia), there was 84% and 88% concordance, respectively. Among 3 cases of ARV-experienced patients with viremia, providers reported 20 different ARV selections, suggesting substantial heterogeneity in ARV preferences in clinical practice.

CONCLUSIONS

HIV-ASSIST is a novel patient-centric educational decision support tool that provides ARV recommendations concordant with experienced HIV providers for a diverse set of patient scenarios.

Importance

Chronic kidney disease (CKD) is the 16th leading cause of years of life lost worldwide. Appropriate screening, diagnosis, and management by primary care clinicians are necessary to prevent adverse CKD-associated outcomes, including cardiovascular disease, end-stage kidney disease, and death.

Observations

Defined as a persistent abnormality in kidney structure or function (eg, glomerular filtration rate [GFR] <60 mL/min/1.73 m2 or albuminuria ≥30 mg per 24 hours) for more than 3 months, CKD affects 8% to 16% of the population worldwide. In developed countries, CKD is most commonly attributed to diabetes and hypertension. However, less than 5% of patients with early CKD report awareness of their disease. Among individuals diagnosed as having CKD, staging and new risk assessment tools that incorporate GFR and albuminuria can help guide treatment, monitoring, and referral strategies. Optimal management of CKD includes cardiovascular risk reduction (eg, statins and blood pressure management), treatment of albuminuria (eg, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers), avoidance of potential nephrotoxins (eg, nonsteroidal anti-inflammatory drugs), and adjustments to drug dosing (eg, many antibiotics and oral hypoglycemic agents). Patients also require monitoring for complications of CKD, such as hyperkalemia, metabolic acidosis, hyperphosphatemia, vitamin D deficiency, secondary hyperparathyroidism, and anemia. Those at high risk of CKD progression (eg, estimated GFR <30 mL/min/1.73 m2, albuminuria ≥300 mg per 24 hours, or rapid decline in estimated GFR) should be promptly referred to a nephrologist.

Conclusions and Relevance

Diagnosis, staging, and appropriate referral of CKD by primary care clinicians are important in reducing the burden of CKD worldwide.

BACKGROUND

The comparative effectiveness of pre- and post-exposure prophylaxis (PrEP and PEP) for men who have sex with men (MSM) is unclear.

SETTING

We conducted a case-control study of MSM who were initially HIV-uninfected during September 1, 2012-June 30, 2016 at San Francisco's only municipal sexually transmitted diseases (STDs) clinic.

METHODS

Each case was matched with up to 3 controls based on age, baseline visit date, and follow-up time. The primary dependent variable was HIV seroconversion; the primary independent variable was exposure to PrEP, PEP, or neither. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals.

RESULTS

Of 638 MSM (161 cases and 477 controls), 137 reported ever taking PrEP, 98 reported taking PEP-only, and 403 took neither. PrEP takers had more non-HIV sexually transmitted diseases during the analysis (72.3% vs. 55.1% vs. 42.4% P < 0.01) and were more likely to report receptive anal sex in the past 3 months (86.5% vs. 80.4% vs. 73.0%; P < 0.01). In the adjusted model, PrEP was associated with lower odds of HIV seroconversion (odds ratio 0.24; 95% confidence interval: 0.13 to 0.46) while PEP use had no effect on HIV acquisition compared with taking neither.

CONCLUSIONS

MSM who ever used PrEP demonstrated equal or higher sexual risk compared with those using neither PrEP nor PEP but had 76% lower odds of HIV seroconversion. MSM who used PEP but never PrEP were no less likely to seroconvert than those using neither. MSM should be offered PrEP. PEP users with ongoing risk of HIV infection should be connected to PrEP after PEP.