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Abstract Background AIDS-associated cryptococcal meningitis has a high mortality. Fluconazole was the only systemic antifungal therapy available in our centre. From 1999–2001 we used low-dose fluconazole (200 mg daily initially), and did not offer therapy to patients perceived to have poor prognoses. In 2001 donated fluconazole became available, allowing us to use standard doses (400 mg daily initially). Antiretroviral therapy was not available during the study period. Methods Retrospective chart review of adult patients before and after the fluconazole donation. Results 205 patients fulfilled the inclusion criteria, 77 before and 128 after the donation. Following the donation fewer patients received no antifungal treatment (5% vs 19%, p = 0.002), and more patients received standard-dose fluconazole (90% vs 6%, p < 0.001). In-hospital mortality was 25%. Impaired consciousness, no antifungal treatment received and cerebrospinal fluid antigen titre > 1,000 were independent predictors of in-hospital mortality. Concomitant rifampicin did not affect in-hospital survival. Thirteen patients were referred to the tertiary referral hospital and received initial treatment with amphotericin B for a mean of 6 days – their in-hospital survival was not different from patients who received only fluconazole (p = 0.9). Kaplan-Meier analysis showed no differences in length of survival by initial treatment with standard or low doses of fluconazole (p = 0.27 log rank test); median survival was 76 and 82 days respectively. Conclusion Outcome of AIDS-associated cryptococcal meningitis is similar with low or standard doses of fluconazole. The early mortality is high. Initial therapy with amphotericin B and other measures may be needed to improve outcome.

Objectives: This study aims to understand the magnitude of and mechanisms underlying the development of cardiovascular events (CVEs) in patients with invasive pneumococcal disease (IPD). We aimed to identify factors that contribute to the occurrence of CVEs within 1 year after admission and discuss implications for patient care., Methods: A multicentered cohort study included adult patients from four Dutch hospitals who had a positive blood culture for Streptococcus pneumoniae and any type of clinical manifestation between 2012 and 2020. Disease characteristics and microbiological data were systematically collected from electronic patient files. The main outcome measures were the occurrence of stroke and acute coronary syndromes (ACS)., Results: Of 914 eligible patients, 4.2% experienced a CVE within 1 year after admission for IPD. ACS mainly occurred in the first 2 weeks, whereas stroke developed throughout follow-up. Although ACS was positively associated with disease severity, the sole independent predictor was alcohol abuse (odds ratio [OR] 3.840, 95% confidence interval [CI] 1.108-13.303). Although stroke occurred in 6.3% of meningitis cases, the best clinical predictor of stroke was a body temperature >39.5 °C at admission (OR 3.117 [1.154-8.423]). In the adult IPD population aged <70 years, pneumococcal serotypes were the primary predictors of ACS (7F; OR 15.733 [1.812-136.632]) and stroke (22F; OR 7.320 [1.193-44.903])., Conclusions: Adverse CVEs were not uncommon after IPD diagnosis and deserve attention, especially in the high-risk groups we identified in our study population. Whether specific serotypes play a role in the development of CVE requires substantiation in further research., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To explore the negative predictive value (NPV) of C-reactive protein (CRP) at admission to exclude complicated disease manifestations of pneumococcal disease., Methods: A Dutch multicentre retrospective cohort study was conducted between 01-01-2012 and 30-06-2020. Adults with positive blood cultures for Streptococcus pneumoniae, whose CRP was measured at admission and whose infection focus was known, were included. Electronic medical and microbiological records were reviewed., Results: Of the 832 bacteraemic patients enrolled, 30% had complicated manifestations of pneumococcal disease; most frequent were pleural effusion (8.9%), pleural empyema (5.4%) and meningitis (7.5%). Compared to solitary pneumonia, patients with pleural effusion and empyema presented with higher CRP levels. Although low CRP levels did not exclude complicated disease in general, a CRP level < 114 mg/L at admission could reliably exclude empyema among adult pneumonia patients with an NPV of 93% and a specificity of 26%. However, in cases where pleural fluid was present, CRP levels were mostly > 114 mg/L, such that suspicion of empyema could only be ruled out in a minority of cases (10%)., Conclusions: Complicated manifestations are prevalent in adult pneumococcal bacteraemia. Low blood CRP levels can reliably exclude the development of pulmonary empyema. Practical value may be largest in settings without thoracic imaging at hand., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: Statins are associated with muscle complaints, including myositis. The mechanism through which statin use causes muscle toxicity is unknown. One of the theories is that statin therapy reduces coenzyme Q10 levels in muscle mitochondria, which leads to muscle injury and myopathy. The aim of the present article is to review published data on the association between coenzyme Q10 and statin-associated myopathy., Recent Findings: Studies have consistently shown that statins reduce coenzyme Q10 levels in serum and that supplementation of coenzyme Q10 increases these levels. However, the effect of statin therapy on coenzyme Q10 levels in muscle has been conflicting. Recently, two pilot studies on coenzyme Q10 supplementation in statin-induced myopathy and one study on the effect of coenzyme Q10 supplementation on serum muscle enzyme levels were published. These three studies were the first randomized trials with coenzyme Q10 supplementation in hypercholesterolemic patients treated with statins. The results of these trials have been contradictory; whereas one seems to support supplementation with coenzyme Q10, the other two do not., Summary: This review summarizes the current evidence on coenzyme Q10 supplementation in statin-induced myopathy. We conclude that the present evidence does not support coenzyme Q10 supplementation in statin-induced myopathy.

Objective: To assess the quality of hypertension care in patients with type 2 diabetes in general practice and identify physician, organizational, and patient factors associated with suboptimal care., Research Design and Methods: Data from 895 randomly selected diabetic patients were extracted from the electronic medical records of 95 general practitioners. Physician and organizational characteristics were collected with a questionnaire. We conducted a multilevel analysis to identify associations with blood pressure registration, hypertension treatment, and achievement of target blood pressure levels., Results: For 652 patients (73%), a blood pressure measurement was recorded in the last year. Of these patients, 132 (20%) reached a target level of 135/85 mmHg. In total, 595 patients were classified as having hypertension, of whom 192 received no treatment (32%), 193 received an ACE inhibitor (32%), and 210 received other antihypertensives. Patients visiting a diabetes facility, referred to a specialist, with a female general practitioner, or with a general practitioner with