Background
We carried out a meta-analysis since there is not enough evidence to recommend for or against therapeutic-dose anticoagulation compared with thromboprophylaxis in noncritically ill ...patients hospitalized with Covid-19.
Methods
We performed a systematic literature search using PubMed, Embase, Cochrane Library, and MedRxiv for randomized trials that included therapeutic-dose with low-molecular-weight heparin (LMW) or thromboprophylaxis with LMW heparin in noncritically ill patients admitted to the hospital with Covid-19. We identified five open-label studies for analysis with a total of 3220 patients. Two independent researchers selected, assessed, and extracted the data in duplicate. The outcomes evaluated were all-cause mortality, progression to invasive mechanical ventilation, incidence of venous thromboembolism, and major bleeding. The studies did not show risk for selection, detection, attrition, or reporting bias.
Results
Therapeutic-dose anticoagulation with LMW heparin compared with thromboprophylaxis with LMW heparin had no significant effect of all-cause death (risk ratio RR 0.85; 95% confidence interval CI 0.67–1.07;
P
= 0.16;
I
2
= 48%), or progression to invasive mechanical ventilation (RR 0.89; CI 0.73–1.08;
P
= 0.24;
I
2
: 0%). Therapeutic-dose anticoagulation significantly reduced the risk of venous thromboembolic disease (RR 0.42; 95% CI 0.28–0.62;
P
= 0.0001;
I
2
= 0%) Number needed to treat = 37. Major bleeding occurred in 1.79% of the patients receiving therapeutic-dose anticoagulation and in 0.97% of those receiving thromboprophylaxis Number needed to harm 125.
Conclusion
Therapeutic-dose anticoagulation in noncritically ill patients with Covid-19 could be indicated for patients at high risk of venous thromboembolic disease and low risk of bleeding.
Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home ...glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay.
We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100.
A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays.
In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.
Background. A major difficulty associated with the use of standard therapy with isoniazid for latent tuberculosis infection is poor patient adherence to therapy because of the prolonged course ...required. Shorter courses of therapy involving ⩾2 drugs have been proposed as an alternative to standard therapy, but they have not undergone enough testing. Methods. We performed a meta-analysis to determine the equivalence of daily short-course therapy with rifampin plus isoniazid for 3 months and standard therapy with isoniazid for 6–12 months. The end points that were evaluated were development of active tuberculosis, severe adverse drug reactions, and death. We searched published information in the Cochrane Library, MEDLINE, and Embase databases, as well as unpublished information in the Cambridge Scientific Abstracts Internet database, Conference Papers Index, AIDS and Cancer Research Abstracts, and ClinicalTrials.gov. We also scanned the reference lists of articles. We only included trials in which individuals were randomly allocated to receive treatment. Two reviewers independently applied the criteria for trial selection, assessed trial quality, and extracted data. Results. Five trials comprising 1926 adults from Hong Kong, Spain, and Uganda were identified. The mean duration of follow-up varied from 13 to 37 months. Overall, development of active tuberculosis was equivalent in association with both regimens (pooled risk difference, 0%; 95% confidence interval CI, -1% to 2%; percentage of total variation across the studies that is the result of heterogeneity rather than chance I2, 0%; P = .86). Severe adverse effects were reported with a similar frequency for both regimens (pooled risk difference, -1%; 95% CI, -7% to 5%) but with statistically significant heterogeneity detected (I2, 78%; P = .001). However, a subanalysis of high-quality trials (including 74% of the sample size) suggested that both regimens were equally safe. In 3 trials (comprising 1390 patients) that provided data on mortality, the regimens showed equivalence (pooled risk difference, -1%; 95% CI, -4% to 2%; I2, 2.7%; P = .38). Conclusion. Short-course therapy with rifampin plus isoniazid was equivalent to standard therapy with isoniazid in terms of efficacy, the proportion of severe side effects that occurred, and mortality.
Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks associated with high production, accumulation and urinary excretion ...of heme precursors, δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). The estimated clinical penetrance for AIP is extremely low (<1%), therefore it is likely that other factors may play an important role in the predisposition to developing attacks. Fasting is a known triggering factor. Given the increased prevalence of insulin resistance in patients and the large urinary loss of succinyl-CoA to produce ALA and PBG, we explore the impact of reduced availability of energy metabolites in the severity of AIP pathophysiology. Classic studies found clinical improvement in patients affected by AIP associated with the administration of glucose and concomitant insulin secretion, or after hyperinsulinemia associated with diabetes. Molecular studies have confirmed that glucose and insulin administration induces a repressive effect on hepatic ALA Synthase, the first and regulatory step of the heme pathway. More recently, the insulin-mimicking α-lipoic acid has been shown to improve glucose metabolism and mitochondrial dysfunction in a hepatocyte cell line transfected with interfering RNA targeting PBGD. In AIP mice, preventive treatment with an experimental fusion protein of insulin and apolipoprotein A-I improved the disease by promoting fat mobilization in adipose tissue, increasing the metabolite bioavailability for the TCA cycle and inducing mitochondrial biogenesis in the liver. In this review, we analyze the possible mechanisms underlying abnormal hepatocellular carbohydrate homeostasis in AIP.
Prior to the appearance of any foot ulcer, there is an increase in the local temperature due to the presence of an underlying inflammatory process. The use of thermometry to identify inflammation ...could make patients increase preventive measures until the inflammation disappears. We carried out a meta-analysis to determine the effectiveness of the daily measurement of the foot temperature in 6 points to prevent the occurrence of foot ulcers in patients with diabetes. Patients with temperature differences >4°F (2.2°C) between left and right corresponding sites should reduce activity and increase preventive measures until temperature is normalized. We searched the literature in MEDLINE, EMBASE, Cochrane Library, Web of Knowledge, and clinicaltrials.gov. We have only included randomized clinical trials where individuals were assigned to receive enhanced care (temperature measurement and standard care) versus standard care (education, self-care practices, and periodic clinical visits). We found 4 trials comprising 462 patients from the United States and Norway that met our inclusion criteria. The duration of follow-up varied from 4.5 to 15 months. Overall, 18 (7.9%) subjects in the enhanced foot care group and 53 (22.6%) in the standard foot care group developed foot ulcers (pooled risk ratio = 0.37; 95% confidence interval = 0.21-0.66; P = .0008; percentage of heterogeneity I2, 25%; P = .26). The number needed to treat was 7 (95% confidence interval = 5-11). The results were robust after analysis by subgroups according to the potential risk of bias in the studies and the duration of follow-up.
To assess the impact of a rapid diagnostic system based on nucleic acid amplification techniques (FilmArray ME) on the diagnosis and treatment of patients with meningitis or encephalitis admitted to ...our emergency department. Between November 2016, and June 2019 we studied 79 samples of cerebrospinal fluid from patients admitted to our emergency department with suspected diagnoses of meningitis or encephalitis. FilmArray ME panel was used routinely in addition to conventional laboratory methods for the identification of microorganisms in cerebrospinal fluid samples (CSF). A total of 46 (58%) patients had clinical and CSF results suggestive of meningitis or encephalitis, and 24 (30%) had a confirmed microbiological diagnosis. Patients' mean age was 41 years (range 2 months to 90 years) and 56% were male. Four patients had been partially treated with antibiotics. FilmArray ME identified 23 cases (1 fungal, 11 bacterial, and 11 viral). Gram staining showed microorganisms in 5 cases (1 fungal, 4 bacterial), and conventional microbiology cultures identified 8 cases (1 fungal and 7 bacterial). The time difference (95% confidence interval) between FilmArray ME and cerebrospinal fluid culture results was 3.2 days (95% CI 2.7–3.7;
P
< 0.001). FilmArray ME results induced modifications in antimicrobial treatment in 27 (59%) patients. The FilmArray ME panel provided a fast and reliable result in a large proportion of patients, even in those patients with culture-negative bacterial meningitis. Use of FilmArray ME can contribute to antimicrobial stewardship.
Background: Describe the profile of patients with obesity in internal medicine to determine the role of adiposity and related inflammation on the metabolic risk profile and, identify various ...“high-risk obesity” phenotypes by means of a cluster analysis. This study aimed to identify different profiles of patients with high-risk obesity based on a cluster analysis. Methods: Cross-sectional, multicenter project that included outpatients attended to in internal medicine. A total of 536 patients were studied. The mean age was 62 years, 51% were women. Patients were recruited from internal medicine departments over two weeks in November and December 2021 and classified into four risk groups according to body mass index (BMI) and waist circumference (WC). High-risk obesity was defined as BMI > 35 Kg/m2 or BMI 30−34.9 Kg/m2 and a high WC (>102 cm for men and >88 cm for women). Hierarchical and partitioning clustering approaches were performed to identify profiles. Results: A total of 462 (86%) subjects were classified into the high-risk obesity group. After excluding 19 patients missing critical data, two profiles emerged: cluster 1 (n = 396) and cluster 2 (n = 47). Compared to cluster 1, cluster 2 had a worse profile, characterized by older age (77 ± 16 vs. 61 ± 21 years, p < 0.01), a Charlson Comorbidity Index > 3 (53% vs. 5%, p < 0.001), depression (36% vs. 19%, p = 0.008), severe disability (64% vs. 3%, p < 0.001), and a sarcopenia score ≥ 4 (79% vs. 16%, p < 0.01). In addition, cluster 2 had greater inflammation than cluster 1 (hsCRP: 5.8 ± 4.1 vs. 2.1 ± 4.5 mg/dL, p = 0.008). Conclusions: Two profiles of subjects with high-risk obesity were identified. Based on that, older subjects with obesity require measures that target sarcopenia, disability, psychological health, and significant comorbidities to prevent further health deterioration. Longitudinal studies should be performed to identify potential risk factors of subjects who progress from cluster 1 to cluster 2.
To assess the effect of early syphilis on HIV viral load (VL) and CD4 cell count in patients with HIV and to analyze factors associated with changes in HIV VL and CD4 cell count.
Multicenter study of ...a series of patients with HIV who were diagnosed with early syphilis infection during 2004 through 2005. Patients who started or changed their highly active antiretroviral therapy (HAART) regimen during the analysis period were excluded.
One hundred eighteen patients were analyzed: 95.8% were men, mean patient age was 38.2 years, 83.9% were homosexual men, 50.8% were on antiretroviral therapy at the time syphilis was diagnosed, and HIV and syphilis diagnoses were coincident in 38 (32.2%) cases. CD4 cell counts were lower during syphilis than before (590 vs. 496 cells/microL; P = 0.0001) and after syphilis treatment (509 vs. 597 cells/microL; P = 0.0001). The HIV VL increased in 27.6% of patients during syphilis. The only factor associated with an HIV VL increase was not being on HAART, and the only factor associated with a CD4 count decrease >100 cells/microL during syphilis was the prior CD4 cell count.
Syphilis infection was associated with a decrease in the CD4 cell count and an increase in the HIV VL in almost one third of the patients. In this series, more than two thirds of the syphilis cases were diagnosed in patients who were previously known to be infected with HIV.
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