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.

Cause-specific long-term mortality rates in patients recovered from community-acquired pneumonia as compared with the general Dutch population.

Insights into long-term mortality, especially into the cause of death after initial recovery from an episode of community-acquired pneumonia (CAP), may help in determining optimal preventive measures in such patients. Prospective observational cohort studies were conducted to compare cause-specific long-term mortality rates for 356 patients who had recovered from CAP with those of the general Dutch population (16.3 million) between 2003 and 2007. The Dutch Municipal Public Records Database and death certificates were used to determine cause-specific mortality rates up to 7 years after discharge. In patients who had recovered from CAP, cumulative 1-year, 5-year and 7-year mortality rates were 17%, 43% and 53%, respectively, as compared with 4%, 19% and 24% for an age-matched and sex-matched population reference cohort. Overall, patients who had recovered from CAP had significantly higher long-term mortality than matched population controls (rate ratio (RR) 3.6; p <0.001). In the years after an episode of CAP, malignancy (27%), chronic obstructive pulmonary disease (COPD) (19%) and cardiovascular disease (16%) were the most frequent causes of death. Only 6% died of pneumonia, as compared with 3.2% in the general population. After initial recovery from an episode of CAP, long-term mortality rates are more than three times as high as in the general population. The causes of long-term mortality were mostly comorbidity-related, and significantly different from those in the general population. After an episode of CAP, optimization of treatment of comorbidities, such as treatment for COPD, might improve long-term survival rates.

Short-course antibiotic treatment in acute exacerbations of chronic bronchitis and COPD: a meta-analysis of double-blind studies.

BACKGROUND: A study was undertaken to determine whether a short course of antibiotic treatment (< or = 5 days) is as effective as the conventional longer treatment in acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease (COPD). METHODS: MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to July 2006. Studies considered eligible were double-blind randomised clinical trials including adult patients > or = 18 years of age with a clinical diagnosis of exacerbation of COPD or chronic bronchitis, no antimicrobial therapy at the time of diagnosis and random assignment to antibiotic treatment for < or = 5 days versus > 5 days. The primary outcome measure was clinical cure at early follow-up on an intention-to-treat basis. RESULTS: 21 studies with a total of 10 698 patients were included. The average quality of the studies was high: the mean (SD) Jadad score was 3.9 (0.9). At early follow-up (< 25 days), the summary odds ratio (OR) for clinical cure with short treatment versus conventional treatment was 0.99 (95% CI 0.90 to 1.08). At late follow-up the summary OR was 1.0 (95% CI 0.91 to 1.10) and the summary OR for bacteriological cure was 1.05 (95% CI 0.87 to 1.26). Similar summary ORs were observed for early cure in trials with the same antibiotic in both arms and in studies grouped by the antibiotic class used in the short-course arm. CONCLUSIONS: A short course of antibiotic treatment is as effective as the traditional longer treatment in patients with mild to moderate exacerbations of chronic bronchitis and COPD.

Costs associated with shorter duration of antibiotic therapy in hospitalized patients with mild-to-moderate severe community-acquired pneumonia.

OBJECTIVES: The optimal duration of antibiotic therapy in patients with uncomplicated pneumonia may be shorter than that recommended in the current guidelines. A shorter duration will probably also lead to a cost reduction. This study evaluates the costs associated with 3 versus 8 day antibiotic therapy and subsequent follow-up in patients hospitalized with mild-to-moderate-severe community-acquired pneumonia. PATIENTS AND METHODS: The economic evaluation was based on primary resource utilization data collected within the framework of a randomized, double blind, placebo-controlled trial. As 3 day therapy was shown to be clinically not inferior to 8 day therapy, the cost-minimization analysis was performed based on direct medical and indirect non-medical costs, estimated from a societal perspective for the 28 days following hospital admission. RESULTS: Lower costs of shorter therapy during hospital admission (euro 209 lower) were partially offset by higher costs for primary healthcare providers (euro 66 higher). The average costs generated per patient by resource utilization during admission and follow-up were estimated as euro 3,959 in the 3 day group versus euro 4,102 in the 8 day group (difference euro 143 in favour of shorter therapy). The difference was affected by changes in assumptions concerning the unit costs for hospital stay but was consistently in favour of shorter therapy. CONCLUSIONS: Shorter duration of antibiotic therapy in hospitalized patients with uncomplicated pneumonia does not result in a substantial substitution of resource utilization to primary healthcare providers. As 3 day antibiotic therapy does not lead to inferior clinical results, these findings support a 3 day therapy as a more efficient strategy.

Three vs. 10 days of amoxycillin-clavulanic acid for type 1 acute exacerbations of chronic obstructive pulmonary disease: a randomised, double-blind study.

The optimal duration of antibiotic treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is unknown. This study compared the outcome of treatment for 3 vs. 10 days with amoxycillin-clavulanic acid of hospitalised patients with AECOPD who had improved substantially after initial therapy for 3 days. Between November 2000 and December 2003, 56 patients with AECOPD were enrolled in the study. Unfortunately, because of the low inclusion rate, the trial was discontinued prematurely. Patients were treated with oral or intravenous amoxycillin-clavulanic acid. Patients who showed improvement after 72 h were randomised to receive oral amoxycillin-clavulanic acid 625 mg or placebo, four times daily for 7 days. The primary outcome measure of the study was clinical cure after 3 weeks and 3 months. Of 46 patients included in the final analysis, 21 were in the 3-day treatment group and 25 were in the 10-day treatment group. After 3 weeks, 16 (76%) of 21 patients in the 3-day treatment group were cured, compared with 20 (80%) of 25 in the 10-day treatment group (difference -3.8%; 95% CI -28 to 20). After 3 months, 13 (62%) of 21 patients were cured, compared with 14 (56%) of 25 (difference 5.9%; 95% CI -23 to 34). Microbiological success, symptom recovery, the use of corticosteroids, the duration of oxygen therapy and the length of hospital stay were comparable for both treatment groups. It was concluded that 3-day treatment with amoxycillin-clavulanic acid can be a safe and effective alternative to the standard 10-day treatment for hospitalised patients with AECOPD who have improved after initial therapy for 3 days.

Development and validation of a short questionnaire in community acquired pneumonia.

BACKGROUND: A short but sensitive questionnaire evaluating changes in respiratory symptoms and well being during the treatment of community acquired pneumonia (CAP) is needed. We have developed a measurement and evaluated its psychometric properties in 67 patients admitted with CAP. METHODS: The patients were asked to indicate the presence and severity of dyspnoea, coughing, coughing up sputum, coughing up sputum with ease, the colour of the sputum, fatigue, fitness, and their state of health. The item fatigue showed substantial overlap with fitness and was therefore excluded. The response of the patients to the remaining eight items was used to calculate a CAP score. RESULTS: The percentage of missing data (0.2-1.7%), floor and ceiling effects (0.2/5.5%), internal consistency (Cronbach alpha = 0.87), and the intraclass correlation coefficient for test-retest reproducibility (0.83) met predefined criteria, indicating good acceptability and reliability. Face and clinical validity were satisfactory. Effect sizes under treatment were large, indicating high responsiveness. CONCLUSION: The newly developed CAP score is a simple, reliable, valid, and highly responsive instrument. This makes it scientifically sound and clinically relevant for measuring outcome when evaluating treatment strategies in CAP.

[Hypoglycaemia after surgery on phaeochromocytoma]. / Hypoglycémie compliquant la chirurgie d'un phéochromocytome.

Few cases of postoperative hypoglycaemia complicating the removal of a phaeochromocytoma have been reported in the literature. We reported one case of hypoglycaemia secondary to the removal of right phaeochromocytoma in a 30-year-old patient. Seven hours after the excision of the tumour, the patient developed a severe hypoglycaemia at 1.67 mmol x l(-1) revealed by seizures completely resolving in 24 h. The hypoglycaemia in this context resulted probably from the massive secretion of insulin by the beta cells of Langerhans islands due to the suppression of alpha-adrenergic inhibition. The prevention of this complication requires the repeated measurement of the capillary glycaemia in the postoperative period. An important supply of carbohydrate may be necessary to maintain a normoglycaemia.

Outcome in adults with juvenile idiopathic arthritis. Comparison of the DUTCH-AIMS2 between JIA and RA.

OBJECTIVES: To compare outcome in adult patients with JIA in childhood with outcome in young adults with RA and to evaluate the use of the DUTCH-AIMS2 in adult JIA patients METHODS: A questionnaire containing the DUTCH-AIMS2 to assess health outcomes (answers ranging from 0-10: 0=best) was sent to 142 adults with JIA (18-40 years). These health outcomes were compared with those of 34 young RA patients (< or = 40 years) from former studies. The DUTCH-AIMS2 was tested for its reliability and validity in adult JIA patients. RESULTS: The response rate was 71%. Disease duration of JIA patients (mean 19.2+/-9.5 years) was longer than in young RA patients (mean 7.8+/-5.3 years). RA patients scored worse than JIA patients in all health status areas with the exception of mobility. The mean health outcome scores were low for all groups (< or = 4.80). The internal consistency and the validity of the DUTCH-AIMS2 were satisfactory. CONCLUSIONS: Overall, the health outcome of oligoarticular and polyarticular adult JIA and young RA patients was quite good. The DUTCH-AIMS2 can be used as an instrument in outcome studies in JIA patients.