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Background: To assess treatment persistence and adherence in men ≥45 years of age with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), using prescription records from the Netherlands IMS Lifelink™ LRx database. Methods: In this retrospective, observational cohort study, we identified men who received combination therapy with an α-blocker plus an antimuscarinic (e.g. solifenacin or tolterodine) between 1 November 2013 and 31 October 2014. Treatment could be received as a fixed-dose combination (FDC) tablet or as two drugs administered together (concomitant therapy), if both combination drugs were prescribed within 30 days. The primary objective was to assess treatment persistence, defined as the time from initiation of combination therapy until first discontinuation of the FDC or at least one of the drugs given concomitantly (i.e. ≥30 days without prescription renewal). Subgroup and sensitivity analyses were conducted to assess persistence by antimuscarinic agent, and with different gap lengths used to define discontinuation (45, 60 and 90 days), respectively. Results: A total of 1891 men received an α-blocker plus an antimuscarinic (FDC, N = 665; concomitant therapy, N = 1226). Median time to discontinuation was significantly longer with FDC versus concomitant therapy (414 vs. 112 days; adjusted hazard ratio [HR] 2.04, 95% confidence interval 1.77, 2.35; p < 0.0001). Persistence at 12 months (51.3% vs. 29.9%) was also significantly greater with FDC compared with concomitant therapy. Assessment of antimuscarinic subgroups showed that median time to discontinuation was longest with solifenacin combinations (214 days) compared with other antimuscarinic combinations (range, 47-164 days; adjusted HR range, 1.27-1.77, p = 0.037). No observable impact on treatment persistence was found by adjusting the gaps used to define discontinuation. Discussion: This study of real-world evidence of men with LUTS/BPH treated with α-blocker plus antimuscarinic combination therapy in the Netherlands showed that treatment persistence was significantly greater in those who received a FDC tablet compared with combination therapy given concomitantly. The study also shows that treatment persistence was extended in men who received combination therapy containing solifenacin compared with other antimuscarinics. Conclusions: Overall, these findings may be useful for prescribers, as improved persistence on-treatment may translate into improved outcomes for men with LUTS/BPH. Further study is warranted to establish the key drivers of persistence in men receiving combination therapy for LUTS/BPH.

The efficacy and safety of recombinant human interferon gamma (rIFN-gamma) in the reduction of opportunistic disease in patients with advanced HIV-1 infection are assessed. A 12-month double-blind, placebo-controlled, multicenter, Phase III trial of rIFN-gamma in HIV-positive patients with CD4100 x 10(9)/liter on stable antiretroviral therapy. Eighty-four patients were allocated treatment on a 1:1 basis to rIFN-gamma or placebo. Patients received rIFN-gamma 0.05 mg/m(2) or 0.9% saline subcutaneously three times weekly for 48 weeks (optional extension to 18 months). The primary end point was the incidence of opportunist infections (CDC categories B/C). Secondary end points included mortality, immunological, and virological parameters. Patients on placebo had a mean of 3.45 opportunist infections (OIs) in the first 48 weeks. Patients treated with rIFN-gamma had a mean of 1.71 OIs (p = 0.04). However, the model showed overdispersion and the inclusion of a dispersion factor raised the p value to 0.13. rIFN-gamma appeared to have a particular effect on the incidence of Candida, herpes simplex, and cytomegalovirus infections. Three-year survival in the rIFN-gamma arm was 28% compared to 18% in the placebo group (not significant). rIFN-gamma-associated side-effects of headache, fatigue, rigors, influenza-like symptoms, depression, myalgia, and granulocytopenia were reversible. There was no evidence for HIV activation. Although not significant, the trend towards decreased opportunistic infections and increased survival warrants consideration of further trials of rIFN-gamma. The study gives additional information on the safety profile of this cytokine.

This report summarizes the results of a series of experimental implantations of polytetrafluoroethylene valves in sheep. Twelve prostheses were implanted in the tricuspid position in weanling (3- to 4-month-old, 26 +/- 3 kg) sheep. The valve sizes were 23 mm (eight animals) and 25 mm (four animals). There were two early deaths, and the 10 survivors were killed in a stepwise manner to get a mineralization profile of the valve. There was one episode of acute thrombosis but no evidence of pulmonary thromboemboli in any animal. In all cases the leaflets were thin and unretracted, but in half of them one cusp or more were stiffened. One valve displayed a fixed outward eversion of the free margin of two leaflets. Macroscopic calcification was detected in seven specimens and always involved the commissural areas. Radiologic studies confirmed this calcium topography and revealed only one case of severe and diffuse mineralization. In most cases the cusps showed a grossly visible pannus that was thinner and less extensive than usually seen in bioprostheses. Examination with light microscopy disclosed a complete lack of infiltrating cells within the cuspal material (made of compact polytetrafluoroethylene). However, those parts of the prostheses made of expanded polytetrafluoroethylene (the material covering the valve frame and the sutures) did show infiltration by host cells and calcium. Mineralized lesions were of extrinsic type, involving fibrin and fibroelastic host tissue accumulated in the inflow aspect of the commissures. Examination with transmission electron microscopy disclosed electron-dense masses surrounded by an electron-lucent granular homogeneous material in areas of mineralization. The time-course evolution of the tissue calcium content shows a moderate mineralization rate (0.46 +/- 0.31 mg/gm of dry-weight material per week of follow-up) and a marginally significant positive correlation between calcium content and follow-up. Our results suggest that the polytetrafluoroethylene valves have a moderate overall calcification rate and that calcium deposits appear to be always related to the commissural region and to the presence of expanded polytetrafluoroethylene.

This report provides retrospective follow-up data on 324 consecutive patients who received a Hancock-I porcine valve in the aortic or the mitral position, or in both positions, between June, 1974, and December, 1976. This analysis included 319 valves (193 mitral, 126 aortic) available for study of the incidence of primary tissue valve failure after 10 to 12.5 years of follow-up. Of the 319 prostheses at risk, 114 instances of primary tissue valve failure occurred. Seventy-three of the failed valves were in the mitral position, and 41 were in the aortic position. The calculated actuarial probability of freedom from primary tissue valve failure was 52 +/- 5% for the mitral and 58 +/- 6% for the aortic prostheses at 12.5 years of follow-up. For patients older than 40 years at the time of operation, the rate of freedom from primary failure was 68 +/- 8% and 55 +/- 6% for aortic and mitral prostheses, respectively, at 12.5 years. Comparison of both actuarial curves disclosed no meaningful difference. However, a tendency toward greater failure rate was observed in the mitral prosthesis group.

Retrospective follow-up data on 458 consecutive patients who received a Hancock, Carpentier-Edwards (C-E) or Ionescu-Shiley (I-S) bioprosthesis in the aortic valve position between April 1978 and December 1981 are reviewed. A total of 461 valves (184 Hancock, 131 C-E and 146 I-S) were available for study of the incidence of primary tissue valve failure after 5 to 9 years of follow-up. Cumulative follow-up was 1,016 patient-years for patients with Hancock valve, 688 for the C-E and 767 for the I-S group. Of the 397 prostheses at risk (154 Hancock, 120 C-E and 123 I-S), 36 instances of primary tissue valve failure occurred (12 Hancock, 7 C-E and 17 I-S). On an actuarial basis, the calculated probability of freedom from primary tissue valve failure was 88 ± 4% for the Hancock group, 87 ± 6% for the C-E and 51 ± 17% for the I-S at 9 years. The linear incidence of tissue valve failure was 1.2 failing valves per 100 patient-years for the Hancock group, 1 for the C-E and 2.2 for the I-S. In a cohort of patients older than 40 years of age at the time of valve replacement, the rate of freedom from primary failure was 98 ± 1%, 87 ± 9% and 44 ± 22% for the Hancock, C-E and I-S groups, respectively, at 9 years. Comparison of actuarial curves disclosed a meaningful difference between the pericardial valve and the Hancock and C-E porcine bioprostheses at 9-year follow-up. These data should have some bearing of practical import not only when comparing different types of bioprostheses, but especially when recommending the appropriate valve replacement for the individual patient.