Recent Publications by CFE Educators

OBJECTIVES

To determine if integration of family planning (FP) and HIV services led to increased use of more effective contraception (i.e. hormonal and permanent methods, and intrauterine devices) and decreased pregnancy rates.

DESIGN

Cohort analysis following cluster randomized trial, when the Kenya Ministry of Health led integration of the remaining control (delayed integration) sites and oversaw integrated services at the original intervention (early integration) sites.

SETTING

Eighteen health facilities in Kenya.

SUBJECTS

Women aged 18-45 receiving care: 5682 encounters at baseline, and 11628 encounters during the fourth quarter of year 2.

INTERVENTION

"One-stop shop" approach to integrating FP and HIV services.

MAIN OUTCOME MEASURES

Use of more effective contraceptive methods and incident pregnancy across two years of follow-up.

RESULTS

Following integration of FP and HIV services at the six delayed integration clinics, use of more effective contraception increased from 31.7% to 44.2% of encounters (+12.5%; Prevalence ratio (PR) = 1.39 (1.19-1.63). Among the twelve early integration sites, the proportion of encounters at which women used more effective contraceptive methods was sustained from the end of the first to the second year of follow-up (37.5% vs. 37.0%). Pregnancy incidence including all 18 integrated sites in year two declined in comparison to the control arm in year one (rate ratio: 0.72; 95% CI 0.60-0.87).

CONCLUSIONS

Integration of FP services into HIV clinics led to a sustained increase in the use of more effective contraceptives and decrease in pregnancy incidence 24 months following implementation of the integrated service model.

TRIAL REGISTRATION

ClinicalTrials.gov NCT01001507.

Eosinophilic pustular folliculitis (EPF) is a rare cutaneous disorder that typically occurs in three clinical contexts: men, individuals who are immunosuppressed or have human immunodeficiency virus, and infants. A fourth subtype occurring 2 to 3 months after hematopoietic stem cell transplantation (HSCT) has recently been described in several adults. We report two cases of EPF arising in children after HSCT. It is important to recognize this form of EPF after HSCT and differentiate it from graft-versus-host disease since it responds readily to topical steroids and appears to have an excellent prognosis.

OBJECTIVE

To examine whether grip strength, gait speed, and the combination of the two physical functioning measures modified the association of systolic BP (SBP) and diastolic BP (DBP) with mortality.

DESIGN

Nationally representative cohort study.

SETTING

Health and Retirement Study.

PARTICIPANTS

7,492 U.S. adults aged ≥65 years.

MEASUREMENTS

Grip strength was measured by a hand dynamometer and classified as normal (≥16 kg for female; ≥26 kg for male) and weak. Gait speed was assessed over a 98.5-inch walk and classified as non-slow (≥0.60 m/s for female; ≥0.52 m/s for male) and slow.

RESULTS

Over an average follow-up time of 6.0 years, 1,870 (25.0%) participants died. After adjustment for socio-demographic, behavioral, and clinical measures, elevated SBP (≥150 mmHg) and DBP (≥90 mmHg) was associated with a 24% (95% CI, 7-43%) and 25% (95% CI, 5-49%) higher mortality among participants with normal grip strength. In contrast, elevated SBP and DBP was associated with a 6% (95% CI, 31 to -27%) and a 16% (95% CI, 46 to -26%) lower mortality among those with weak grip strength (P-values of interactions: both=.07). The inverse relations between BP with death were most pronounced among slow walkers with weak grip strength. The HRs of elevated SBP and DBP for death was 0.85 (95% CI, 0.56-1.29) and 0.53 (95% CI, 0.30-0.96), respectively, and was substantially different from non-slow walkers with normal grip strength (HR = 1.24 and 1.15, respectively; P-values of interactions: both .001). Therefore, associations of BP with death varied modestly by gait speed.

CONCLUSION

Grip strength modified the association of BP with death. Combination of grip strength and gait speed has incremental value for modifying the association of BP with death.

BACKGROUND

The MitraClipsystem is a transcatheter-based therapeutic option for patients with chronic mitral regurgitation (MR) who are at high risk for surgery. A prospective, multicenter, single-arm study was initiated to confirm the transferability of this system to Japan.Methods and Results:Patients with symptomatic chronic moderate-to-severe (3+) or severe (4+) functional or degenerative MR with a Society of Thoracic Surgery (STS) score ≥8%, or the presence of 1 predefined risk factor were enrolled. Patients with left ventricular (LV) ejection fraction (EF) 30% were excluded. MR severity and LV function were assessed by an independent echocardiography core lab. Primary outcome included major adverse events (MAE) at 30 days and acute procedural success (APS). A total of 30 patients (age: 80±7 years; STS score: 10.3%±6.6%) were treated with the MitraClip. At baseline, all patients had MR 3+/4+ with 53%/47% patients with degenerative/functional etiology with mean LVEF of 50.2±12.8%, and 37% of patients were NYHA class III/IV. APS was achieved in 86.7% with no occurrence of MAE. At 30 days, 86.7% of patients had MR ≤2+ and 96.7% were NYHA class I/II.

CONCLUSIONS

The MitraClipprocedure resulted in clinically meaningful improvements in MR severity, function and quality of life measures, and low MAE rates. These early results suggest the transferability of this therapy to appropriately selected Japanese patients. (Trial Registration: clinicaltrials.gov Identifier NCT02520310.).

High-dose ionising radiation is associated with circulatory disease. Risks associated with lower-dose (0.5 Gy) exposures remain unclear, with little information on risk modification by age at exposure, years since exposure or dose-rate. Tuberculosis patients in Canada and Massachusetts received multiple diagnostic x-ray fluoroscopic exposures, over a wide range of ages, many at doses 0.5 Gy. We evaluated risks of circulatory-disease mortality associated with 0.5 Gy radiation exposure in a pooled cohort of 63,707 patients in Canada and 13,568 patients in Massachusetts. Under 0.5 Gy there are increasing trends for all circulatory disease (n = 10,209; excess relative risk/Gy = 0.246; 95% CI 0.036, 0.469; p = 0.021) and for ischaemic heart disease (n = 6410; excess relative risk/Gy = 0.267; 95% CI 0.003, 0.552; p = 0.048). All circulatory-disease and ischaemic-heart-disease risk reduces with increasing time since exposure (p  0.005). Over the entire dose range, there are negative mortality dose trends for all circulatory disease (p = 0.014) and ischaemic heart disease (p = 0.003), possibly due to competing causes of death over this dose interval.These results confirm and extend earlier findings and strengthen the evidence for circulatory-disease mortality radiation risk at doses 0.5 Gy. The limited information on well-known lifestyle/medical risk factors for circulatory disease implies that confounding of the dose trend cannot be entirely excluded.

CONTEXT

Optimal management for patients with intermediate-risk (IR) prostate cancer (PCa) remains controversial. Clinical metrics provide guidance on appropriate management options.

OBJECTIVE

To report estimates for clinically relevant outcomes in men with IR PCa based on clinical and pathological features.

EVIDENCE ACQUISITION

PubMed and programs from key 2015 uro-oncology congresses were searched using the terms "intermediate", "Gleason 3 + 4", "Gleason 4 + 3", "active surveillance", "treatment", "adverse pathology", AND "prostate cancer." Articles meeting prespecified criteria were retrieved. Bibliographies were scanned for additional relevant references.

EVIDENCE SYNTHESIS

Men with IR PCa have a wide range of predicted clinically relevant outcomes. Within the IR category, estimate ranges for adverse surgical pathology and 5-yr disease progression are 15-64% and 21-91%, respectively. Clinical parameters and predictive nomograms refine these estimates, but do not uniformly differentiate favorable and unfavorable IR PCa. Variations in study design and data quality in source manuscripts mandate caution in interpreting results.

CONCLUSIONS

Outcomes in IR PCa are heterogeneous. Refinements in personalized risk assessment are needed to better select IR PCa patients for surveillance.

PATIENT SUMMARY

Current and future risk stratification tools may provide additional information to identify men with intermediate-risk prostate cancer who may consider active surveillance.

Disseminated acanthamoebiasis is a rare, often fatal, infection most commonly affecting immunocompromised patients. We report a case involving sinuses, skin, and bone in a 60-year-old woman 5 months after heart transplantation. She improved with a combination of flucytosine, fluconazole, miltefosine, and decreased immunosuppression. To our knowledge, this is the first case of successfully treated disseminated acanthamoebiasis in a heart transplant recipient and only the second successful use of miltefosine for this infection among solid organ transplant recipients. Acanthamoeba infection should be considered in transplant recipients with evidence of skin, central nervous system, and sinus infections that are unresponsive to antibiotics. Miltefosine may represent an effective component of a multidrug therapeutic regimen for the treatment of this amoebic infection.

Pain-producing animal venoms contain evolutionarily honed toxins that can be exploited to study and manipulate somatosensory and nociceptive signaling pathways. From a functional screen, we have identified a secreted phospholipase A2 (sPLA2)-like protein, BomoTx, from the Brazilian lancehead pit viper (). BomoTx is closely related to a group of Lys49 myotoxins that have been shown to promote ATP release from myotubes through an unknown mechanism. Here we show that BomoTx excites a cohort of sensory neurons via ATP release and consequent activation of P2X and/or P2X purinergic receptors. We provide pharmacological and electrophysiological evidence to support pannexin hemichannels as downstream mediators of toxin-evoked ATP release. At the behavioral level, BomoTx elicits nonneurogenic inflammatory pain, thermal hyperalgesia, and mechanical allodynia, of which the latter is completely dependent on purinergic signaling. Thus, we reveal a role of regulated endogenous nucleotide release in nociception and provide a detailed mechanism of a pain-inducing Lys49 myotoxin from species, which are responsible for the majority of snake-related deaths and injuries in Latin America.