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Response of renin, aldosterone and antidiuretic hormone to furosemide and furosemide-triamterene combination.

Plasma renin activity (PRA), antidiuretic hormone (ADH), urinary aldosterone excretion (U-Aldo) and electrolyte excretions were studied in a randomized study after furosemide (80 mg) (F), furosemide + triamterence (80 + 100 mg) (F + T), and after placebo were administered to seven healthy volunteers. F + T preparation showed a slower absorption of furosemide, a slower natriuresis and a slower excretion of potassium as compared to F-präparation. After application of the diuretics, PRA reached the maximal level in four hours, three times higher than the control level after F and four times higher after F + T. At 24 hrs after drug intake PRA did not differe from the control level. No significant difference could be found between F and F + T. U-Aldo of 24 hrs increased 1.9-fold after F and 2.2-fold after F + T, as compared with placebo. Between the individual natriuretic and hormonal responses no correlation could be found. After F + T, U-Aldo and U-K showed a positive correlation (P < 0.05). ADH did not change after diuretics from the pretreatment fasting level. The results show a fast but transient response of the renin-aldosterone system after furosemide and the furosemide-triamterene combination which could not be correlated with the natriuretic effects. The result differs from that found earlier with hydrochlorothiazide.

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Safety Outcomes of Apixaban Compared With Warfarin in Patients With End-Stage Renal Disease.

Current guidelines make no specific recommendations on the selection of direct oral anticoagulants for the prevention and treatment of venous thromboembolism in patients with end-stage renal disease (ESRD) receiving hemodialysis. Based on these guidelines, warfarin remains the anticoagulant of choice in these patients. To compare bleeding rates in patients receiving apixaban or warfarin with ESRD undergoing chronic hemodialysis. This was a single-center, retrospective, institutional review board-approved cohort analysis. Patients with ESRD undergoing chronic hemodialysis and receiving anticoagulation therapy with either apixaban or warfarin were included in this study. All data were collected from paper charts and electronic medical records and included documentation of bleeding events and related interventions. The primary outcome of this study was clinically relevant major bleeding events. Secondary outcomes included clinically relevant nonmajor bleeding events and minor bleeding events. A total of 160 patients were included in this study (warfarin group, n = 120; apixaban group, n = 40). There were 7 major bleeding events in the warfarin group compared with zero in the apixaban group ( P = 0.34). There were similar rates of clinically relevant nonmajor bleeding events (12.5% vs 5.8%, P = 0.17) and minor bleeding (2.5% vs 2.5%, P = 0.74) events in patients receiving apixaban and warfarin. There were no observed differences in bleeding rates in patients receiving apixaban compared with those receiving warfarin. Apixaban may be a cautious consideration in hemodialysis patients until there is further insight into the effect of subsequent, multiple doses on drug accumulation and clinical outcomes.

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Efficacy of metformin on pregnancy complications in women with polycystic ovary syndrome: a meta-analysis.

To evaluate the efficacy of metformin administration throughout pregnancy on pregnancy-related complications in women with polycystic ovary syndrome (PCOS). MEDLINE and ScienceDirect were searched to retrieve relevant trials. The endpoint was the incidence of complications of pregnancy, gestational diabetes mellitus (GDM), pre-eclampsia (PE), miscarriage and premature birth included. Five studies with 502 PCOS patients with metformin administration throughout pregnancy and 427 controls who used metformin just to get conception were included in our meta-analysis. In study group, a significantly lower change of emerging miscarriage and premature birth was observed, the pooled relative risk (RR) was 0.32 (95% confidence interval (CI): 0.19-0.56) for miscarriage and 0.40 (95%CI: 0.18-0.91) for premature birth. No significant difference was demonstrated in emerging GDM and PE. Metformin therapy throughout pregnancy can reduce the RR of miscarriage and premature birth incidence in PCOS patients with no serious side effects.

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Randomized Phase II Study of Afatinib Plus Simvastatin Versus Afatinib Alone in Previously Treated Patients with Advanced Nonadenocarcinomatous Non-small Cell Lung Cancer.

This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC). Patients with advanced NA-NSCLC who progressed after one or two chemotherapy regimens were randomly assigned to a simvastatin (40 mg/day) plus afatinib (40 mg/day) (AS) arm or to an afatinib (A) arm. The primary endpoint was response rate (RR). Sixty-eight patients were enrolled (36 in the AS arm and 32 in the A arm). The RR was 5.7% (95% confidence interval [CI], 0.7 to 19.2) for AS and 9.4% (95% CI, 2.0 to 25.0) for A (p=0.440). In arms AS and A, the median progression-free survival (PFS) was 1.0 versus 3.6 months (p=0.240) and the overall survival was 10.0 months versus 7.0 months (p=0.930), respectively. Skin rash, stomatitis, and diarrhea were the most common adverse events in both arms. More grade 3 or 4 diarrhea was observed in arm A (18.8% vs. 5.6% in arm AS). In all patients, the median PFS for treatment including afatinib was not correlated with the status of epidermal growth factor receptor (EGFR) mutation (p=0.122), EGFR fluorescence in situ hybridization (p=0.944), or EGFR immunohistochemistry (p=0.976). However, skin rash severity was significantly related to the risk of progression for afatinib (hazard ratio for skin rash grade ≥ 2 vs. grade < 2, 0.44; 95% CI, 0.25 to 0.78; p=0.005). There were no significant differences in the efficacy between AS and A arms in patients with NA-NSCLC.

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Infective endocarditis and the dental practitioner: a review of 53 cases involving litigation.

To review episodes of infective endocarditis involving dental procedures that have resulted in litigation and to determine if any clinical recommendations can be obtained. 13-year retrospective study. Patient records were analysed to identify the probable cause of infective endocarditis. All were judged to be caused by dental manipulations on the basis of dental procedure, cardiac pathology, infecting micro-organism and time between onset of infection and dental manipulation. Cases were analysed to check if appropriate national guidelines on antibiotic prophylaxis were followed. Status of patient dental records was also evaluated. Dental procedures implicated in infective endocarditis were exodontia (23), scaling (21), root canal therapy with extra-canal instrumentation (7) and minor oral surgery (2). No medical history was recorded in 10 patients. In a further 31 medical history was inadequate or out of date. Dentists involved with these cases failed to give prophylactic antibiotics (48), prescribed incorrect antibiotics (2), or gave antibiotics at inappropriate times (2). There was one episode of prophylaxis with amoxycillin failing despite it being given correctly. If litigation is to be avoided dental practitioners must keep accurate dental records, take an appropriate medical history that is kept up to date and adhere to national guidelines on antibiotic prophylaxis.

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