Aims To evaluate whether the addition of hydrochlorothiazide (HCTZ) to intravenous furosemide is a safe and effective strategy for improving diuretic response in acute heart failure (AHF). Methods and results A prospective, double-blind, placebo-controlled trial, including patients with AHF randomized to receive HCTZ or placebo in addition to an intravenous furosemide regimen. The coprimary endpoints were changes in body weight and patient-reported dyspnoea 72 h after randomization. Secondary outcomes included metrics of diuretic response and mortality/rehospitalizations at 30 and 90 days. Safety outcomes (changes in renal function and/or electrolytes) were also assessed. Two hundred and thirty patients (48% women, 83 years) were randomized. Patients assigned to HCTZ were more likely to lose weight at 72 h than those assigned to placebo [−2.3 vs. −1.5 kg; adjusted estimated difference (notionally 95% confidence interval) −1.14 (−1.84 to −0.42); P = 0.002], but there were no significant differences in patient-reported dyspnoea (area under the curve for visual analogue scale: 960 vs. 720; P = 0.497). These results were similar 96 h after randomization. Patients allocated to HCTZ showed greater 24 h diuresis (1775 vs. 1400 mL; P = 0.05) and weight loss for each 40 mg of furosemide (at 72 and at 96 h) (P < 0.001). Patients assigned to HCTZ more frequently presented impaired renal function (increase in creatinine >26.5 μmoL/L or decrease in eGFR >50%; 46.5 vs. 17.2%; P < 0.001), but hypokalaemia and hypokalaemia were similar between groups. There were no differences in mortality or rehospitalizations. Conclusion The addition of HCTZ to loop diuretic therapy improved diuretic response in patients with AHF.

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The use of fluorinated quinolones for prophylaxis of infections in neutropenic cancer patients has led to a reduction of infections with gram-negative enteric bacilli, but there is concern about the emergence of antibiotic-resistant enterobacterial infections and a rise of gram-positive bacteremias. Due to these concerns, in mid-1995 the use of prophylactic norfloxacin was discontinued in our unit. In order to evaluate the impact of this measure on the infectious morbidity in our unit, 91 severe neutropenic episodes in 58 patients with hematologic malignancies who did not receive norfloxacin prophylaxis (NO group) were closely matched to 91 episodes in 60 patients who received norfloxacin prophylaxis (NORFLO group). There were no differences in the incidence of febrile neutropenia, fever of unknown origin or bacteremia during the first febrile episode. There was a trend for a higher rate of coagulase-negative staphylococcal bacteremia in the NORFLO group (5 vs. 11 cases in the NO and NORFLO groups, respectively, p = NS). Enterobacterial bloodstream infections were more frequent in the NO group (13 vs. 2 cases, respectively, p = 0.01), especially Escherichia coli (9 vs. 1 case, respectively, p = 0.01). Twelve of 13 enterobacterial isolates in the NO group were sensitive to the fluoroquinolones vs. 0/2 in the NORFLO group (p = 0.07). We conclude that the abrupt discontinuation of norfloxacin prophylaxis in our ward led to a rapid increase in the rate of fluoroquinolone-susceptible enterobacterial infections, with a scarce impact on infectious morbidity. This suggests that the selection of resistant flora in an inpatient ward by prophylactic antimicrobials may be reversible following the discontinuation of the prophylactic agent(s).

The introduction of PARP inhibitors (PARPi) in prostate cancer is a milestone and provides a pathway to hope in fighting this disease. It is the first time that drugs, based on the concept of synthetic lethality, have been approved for prostate cancer. In addition, it is also the first time that genetic mutation tests have been included in the therapeutic algorithm of this disease, representing a significant step forward for precision and personalized treatment of prostate cancer. The objectives of this review are: (1) understanding the mechanism of action of PARPi in monotherapy and combinations; (2) gaining insights on patient selection for PARPi; (3) exposing the pivotal studies that have allowed its approval, and; (4) offering an overview of the ongoing trials. Nevertheless, many unsolved questions remain, such as the number of patients who could potentially benefit from PARPi, whether to use PARPi in monotherapy or in combination, and when is the best time to use them in advanced or localized disease. To answer these and other questions, many clinical trials are underway. Some of them have recently demonstrated promising results that may favor the introduction of new combinations in metastatic castration-resistant prostate cancer.