Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients.

BACKGROUND: The global push for the use of hydroxychloroquine (HCQ) and chloroquine (CQ) against COVID-19 has resulted in an ongoing discussion about the effectivity and toxicity of these drugs. Recent studies report no effect of (H)CQ on 28-day mortality. We investigated the effect of HCQ and CQ in hospitalized patients on the non-ICU COVID-ward. METHODS: A nationwide, observational cohort study was performed in The Netherlands. Hospitals were given the opportunity to decide independently on the use of three different COVID-19 treatment strategies: HCQ, CQ, or no treatment. We compared the outcomes between these groups. The primary outcomes were 1) death on the COVID-19 ward, and 2) transfer to the intensive care unit (ICU). RESULTS: The analysis included 1064 patients from 14 hospitals: 566 patients received treatment with either HCQ (n = 189) or CQ (n = 377), and 498 patients received no treatment. In a multivariate propensity-matched weighted competing regression analysis, there was no significant effect of (H)CQ on mortality on the COVID ward. However, HCQ was associated with a significantly decreased risk of transfer to the ICU (hazard ratio (HR) = 0.47, 95% CI = 0.27-0.82, p = 0.008) when compared with controls. This effect was not found in the CQ group (HR = 0.80, 95% CI = 0.55-1.15, p = 0.207), and remained significant after competing risk analysis. CONCLUSION: The results of this observational study demonstrate a lack of effect of (H)CQ on non-ICU mortality. However, we show that the use of HCQ - but not CQ - is associated with a 53% reduction in risk of transfer of COVID-19 patients from the regular ward to the ICU. Recent prospective studies have reported on 28-day, all-cause mortality only; therefore, additional prospective data on the early effects of HCQ in preventing transfer to the ICU are still needed.

[An older man with a supraclavicular mass]. / Een oudere man met een supraclaviculaire zwelling.

An 80-year-old man, originally from Vietnam, was examined for a painful supraclavicular mass on the right side. Puncture and aspiration of the mass revealed purulent fluid. Examination of the aspirate showed acid-fast bacteria, consistent with tuberculous lymphadenitis. The patient was successfully treated with a 4-drug regimen.

Validation of the 1 µg short synacthen test: an assessment of morning cortisol cut-off values and other predictors.

BACKGROUND: Clinical practice shows that many low-dose short synacthen tests (LD-SSTs) for diagnosing adrenal insufficiency in an outpatient setting have a normal outcome and could be considered superfluous. The objective of this study is to provide a guideline to safely reduce the number of unnecessarily performed LD-SSTs. METHODS: Data of LD-SSTs performed in outpatients were collected. Optimal morning cortisol cut-off values were determined using ROC analysis. Subsequently the predictive value of several variables was tested using univariable and multivariable logistic regression analyses. RESULTS: A morning cortisol lower cut-off value of 145 nmol/l (specificity 89.9%, positive predictive value 90.0%) and an upper cut-off value of 375 nmol/l (sensitivity 100.0%, negative predictive value 100.0%) were found. Chronic fatigue symptoms and symptoms of hypotension or orthostasis as the main reason for performing the test predict a normal outcome. The use of glucocorticosteroids predicts an abnormal outcome of the LD-SST. Oral, topical, nasal and inhaled glucocorticosteroids are each significant predictors when analysed specifically for predicting central adrenal insufficiency. CONCLUSION: By using morning cortisol cut-off values of 145 nmol/l and 375 nmol/l instead of the conventional cut-off values, the number of LD-SSTs performed in an outpatient setting can be reduced by 12%, while maintaining high sensitivity and specificity. Furthermore, the outcome of the LD-SST can be predicted by additional variables such as the indication for performing the test and the use of glucocorticosteroids. Different routes of administration of glucocorticosteroids such as inhalation or topical use should be taken into account when central insufficiency is suspected.

Acute hepatitis C in the Netherlands: characteristics of the epidemic in 2014.

Within the Dutch Acute HCV in HIV Study, a surveillance system was initiated to estimate the incidence of hepatitis C virus (HCV) infections in 2014. Following the Dutch HIV treatment guidelines, HIV-positive men having sex with men (MSM) in 19 participating centers were screened. Ninety-nine acute HCV infections were reported, which resulted in a mean incidence of 11 per 1000 patient-years of follow-up. Unfortunately, the HCV epidemic among Dutch HIV-positive MSM is not coming to a halt.

Accurate and fast diagnostic algorithm for febrile urinary tract infections in humans.

BACKGROUND: The urine dipstick that detects nitrite and leukocyte esterase, and urine sediment is commonly used to diagnose or exclude urinary tract infections (UTIs) as the source of infection in febrile patients admitted to the emergency department of Dutch hospitals. However, the diagnostic accuracy of the urine dipstick and urine sediment has never been studied in this specific situation. METHODS: Urinary samples of 104 febrile consecutive patients were examined. Urine culture with ≥ 10(5) colonies/ml of one or two known uropathogen was used as the gold standard. The diagnostic value of the urine dipstick, urine sediment and Gram stain at various cut-off points was determined and used to develop a new diagnostic algorithm. This algorithm was validated in a new group of sepsis patients based on systemic inflammatory response syndrome (SIRS) criteria. RESULTS: A positive nitrite on the urine dipstick (specificity 99%) rules in UTI. This is the first step of our diagnostic algorithm. The second step is to exclude UTI by absence of bacteria in the urine sediment (sensitivity 94%). The third and last step is the number of leucocytes/high-power field (hpf) in the urine sediment. Less than 10 leucocytes/hpf makes UTI unlikely whereas ≥ 10 leucocytes/hpf indicates UTI. In contrast to urine dipstick and/or urine sediment results alone, our algorithm showed both a high sensitivity (92%) and specificity (92%) and was validated in a new sepsis population. CONCLUSION: Our accurate and fast diagnostic algorithm, which combines the selective results of urine dipstick and urine sediment, can be easily used to diagnose UTI in febrile patients at the emergency department of Dutch hospitals.

Sex hormone binding globulin deficiency due to a homozygous missense mutation.

CONTEXT: SHBG is known as the major sex steroid binding protein in plasma, and it regulates the bioavailability of both T and estradiol levels required for effects on target tissues. We identified a man with an undetectable SHBG concentration in combination with low total T. He presented with a 7-year history of muscle weakness, fatigue, and a low libido. OBJECTIVES: To determine the cause of the SHBG deficiency, we employed both genetic analysis of the SHBG gene and transgene SHBG expression. RESULTS: Genetic analysis identified a novel homozygous missense mutation that was predicted to be deleterious for protein function. Transgene expression showed that the mutation resulted in a block in SHBG secretion accompanied by increased expression of the endoplasmic reticulum molecular chaperone HSPA5. The mutation results in accumulation of the mutant SHBG within the cell and failure to secrete the mutant protein. Screening of family members identified one sister who was also deficient for SHBG. CONCLUSIONS: We have identified a family with a missense mutation within the SHBG gene, which results in a complete deficiency of plasma SHBG in the homozygous state. Although total T level was low in the male patient, it did not interfere with normal gonadal development and spermatogenesis, suggesting a limited role of SHBG in sexual maturation and male physiology.

Severe diffuse interstitial pneumonia due to Mycoplasma pneumoniae in a patient with respiratory insufficiency.

We report a 25-year-old man presenting with high fever, dyspnoea and somnolence. The presence of severe diffuse interstitial pneumonia with extrapulmonary symptoms, such as myositis and subclinical haemolysis, strongly suggested an infection by Mycoplasma pneumoniae. This diagnosis was supported by high titres of cold agglutinins and a positive Coombs test, and directly confirmed by specific IgM serological tests. After initiation of the appropriate antimicrobial treatment mechanical ventilation could be avoided and the patient showed a slow but complete clinical recovery. This diagnosis should be considered in any febrile patient with hypoxaemia and diffuse interstitial pneumonia, and rapid initiation of appropriate antibiotic treatment seems to be crucial for a favourable outcome.

[Devastating community-acquired Staphylococcus aureus bacteremia]. / Verwoestende bacteriëmie met Staphylococcus aureus van buiten het ziekenhuis.

Three patients, two men aged 52 and 62 years and a woman aged 83 years, experienced non-specific flu-like symptoms for a few days but subsequently developed a complicated disease with multiple metastatic infections and endocarditis due to bacteraemia. Only the man aged 62 years had a port of entry, a finger wound. Two patients died. Community-acquired S. aureus bacteraemia is a much more serious disease than nosocomial bacteraemia. The community-acquired bacteraemia is characterised by the absence of a primary focus and non-specific flu-like symptoms in the beginning. This results in a long-duration bacteraemia with a high incidence of metastatic infections, endocarditis and a high mortality rate. A multidisciplinary treatment approach with a careful search for and treatment of endocarditic and metastatic infections in combination with long-duration, high-dose antibiotics is warranted.