Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis.

OBJECTIVES: Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis. METHODS: We searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012-2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472). RESULTS: Seven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89-98; I2=23%) and 88% (95% CI, 83-92; I2=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3-222.2; I2=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92-0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity. CONCLUSIONS: Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis.

Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents.

AIMS: We aimed to determine the efficacy and safety of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists to prevent worsening urinary albumin-to-creatinine ratio as an early biomarker of diabetes kidney disease. METHODS: A total of 178 patients with type 2 diabetes and obesity received combination treatment with SGLT2i added to GLP1ra (n = 76), GLP1ra added to SGLT2i (n = 50) or GLP1ra plus SGLT2i from start (n = 52), according to investigators´ best clinical judgement. Major outcomes assessed at 26 weeks were changes in urine albumintocreatinine-ratio (UACR), estimated glomerular filtration rate (eGFR), glycated haemoglobin, body weight and systolic blood pressure. RESULTS: All patients (58.6% men, mean age 61.9 ± 10.0 years) completed the study. Baseline HbA1c, weight and eGFR levels were 8.2 ± 0.9%, 109.9 ± 19 kg and 83.3 ± 19.6 mL/min/m2 , respectively. At 26 weeks, we found significant reductions in HbA1c (1.16%), weight (5.17 kg) and systolic blood pressure (8.13 mmHg). The reduction in UACR was 15.14 mg/g (95% CI 8.50-22.4) (-24.6 ± 64.7%), which was greatest in the group of patients with SGLT2i added on to GLP1ra therapy (116.7 mg/g; 95% CI: 54-296.5 mg/g; P < .001. Patients with urinary albumin-to-creatinine ratio ≥30 mg/g, showed a higher declines (63.18 mg/g [95% CI 44.5-104.99]) (-56 ± 65.9%). The greatest reduction in urinary albumin-to-creatinine ratio was obtained when SGLT2i was added to GLP1ra (116.7 mg/g). The eGFR did not significantly change along the study period. CONCLUSION: Our results show the beneficial effect of GLP1ra and SGLT2i combination therapy on early biomarkers of diabetes kidney disease such as albuminuria and in other significant outcomes for diabetes control.

Short-course treatment of latent tuberculosis infection in patients with rheumatic conditions proposed for anti-TNF therapy.

Tuberculosis reactivation is a serious threat in patients treated with anti-tumour necrosis factor therapy. A 6-month regimen with isoniazid is considered as the standard of care, but patient adherence is a major shortcoming. We carried out an open-label, single-arm intervention study to assess the efficacy, the completion rate and the tolerability of a 3-month regimen with isoniazid plus rifampin. Seventy-eight patients with rheumatic conditions proposed for anti-tumour necrosis factor (TNF) therapy and at risk of tuberculosis reactivation were offered to participate in the study. Nine patients were excluded due to deficit of glucose-6-phosphate dehydrogenase (n = 1), salicylate hypersensitivity (n = 1), declining to participate (n = 5) or preferring a 6-month isoniazid regimen (n = 6). Sixty-nine patients were treated with a 3-month regimen with isoniazid and rifampin. No cases of tuberculosis were observed after a mean follow-up of 90 months (range from 66 to 121 months). Sixty (87 %) patients completed the therapy. Nine (13 %) patients discontinued the therapy due to rifampin hypersensitivity (n = 1), symptomatic grade 3-4 hepatotoxicity (n = 2), abdominal discomfort (n = 2), pruritus (n = 1), arthritis (n = 1) and personal concerns (n = 2). A short course treatment with isoniazid and rifampin provided efficacy, good tolerability and good completion rate in patients with rheumatic conditions proposed for anti-TNF therapy.

[Use of pulse oximetry as screening method for peripheral arterial disease in patients admitted to a general medicine service]. / Utilidad de la pulsioximetría en el cribado de enfermedad arterial periférica en pacientes ingresados en servicios de medicina interna.

INTRODUCTION: Ankle-brachial index measured by a continuous wave Doppler device remains as the reference method for office diagnosis of peripheral arterial disease. This method is time consuming, requires an appropriate device and training of the examiner. We evaluated the usefulness of pulse oximetry as an easier method to screen for peripheral arterial disease. METHODS: A total of 110 subjects were selected by opportunistic sampling among patients admitted to a general medicine service. Entry criteria were age older than 50 years and having an additional cardiovascular risk factor. Patients with known cardiovascular disease were excluded. We measured oxygen saturation (SaO2) by means of a pocket finger tip pulse oximeter at 4 limbs. SaO2 was measured at right and left index fingers and great toes with patient lying and after elevating the foot 30 cm above the bed. We considered as abnormal a difference in SaO2 greater than 2% between fingers and toes. Brachial index was estimated by means of a handheld Doppler device. RESULTS: The prevalence of peripheral arterial disease was 10% (95% confidence interval [CI], 6%-14%). Pulse oximetry has sensitivity 12% (95%CI, 4%-37%), specificity 67% (95%CI, 60%-74%), positive likelihood ratio 0.43 (95%CI, 0.11-1.19), negative likelihood ratio 1.27 (95%CI, 0.91-1.45) and area under the receiving operating characteristics curve 0.75 (95%CI, 0.67-0.82). CONCLUSIONS: Pulse oximetry showed low accuracy as screening method for peripheral arterial disease. Simpler and more accurate devices than ankle-brachial index measured by Doppler are necessary to ease the screening of peripheral arterial disease.

Impact of syphilis infection on HIV viral load and CD4 cell counts in HIV-infected patients.

OBJECTIVES: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

[Interruption of antiretroviral therapy in chronically HIV-infected patients]. / Interrupción del tratamiento antirretroviral en pacientes con infección crónica por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: To describe the immunological, virological and clinical outcomes of HIV-infected patients who stop antiretroviral therapy (ART) and to identify the factors related to durability. PATIENTS AND METHOD: Retrospective study of patients who interrupt therapy after six months without clinical events, level of CD4+ > or = 500 cells/microl and HIV RNA > or = 5,000 copies/ml (3.7 log10). RESULTS: In October 2004, 44 patients were included, 32 (72%) of them were stables after one year of ART cessation (group A) and 12 (28%) patients had to restart therapy due to a decreased CD4+ count < 300 cells/microl (group B). Both groups were compared. CD4 cell count nadir (414 cells/microl [199] versus 171 cells/microl [107]; p = 0.000) and CD4+ count level at time of ART stop (920 [302] cells/microl versus 633 cells/microl [177] p = 0.004) showed differences with statistical significance. The most important CD4+ count fall was observed at third month after stopping ART; 588 cells/microl (288) on group A and 382 cells/microl (167) on group B. The mean time without ART was 27 months on group A and 7 months on group B. Two patients had acute retroviral syndrome, and one had Pneumocystis jiroveci pneumonia. Cholesterol levels were 199 mg/dl (42) and triglycerides 257 mg/dl (271) on ART and during interruption decreased to 155 (38) and 165 (122) mg/dl respectively. After multivariate analysis, a CD4+ count nadir > 200 cells/microl (p = 0,0005; OR = 0,12; 95% CI, 0.036-0,398) and a CD4+ count at time of ART stop > 800 cells/microl (p = 0,04; OR: 0,11; CI 95%: 0,015-0,936) were independently related to durability of therapy interruption. CONCLUSIONS: Prolonged discontinuation of ART guided by CD4+ response causes a low morbi-mortality. The cell count CD4+ nadir and the CD4+ count at time of ART cessation are protective factors of durability. An improvement of metabolic parameters is observed during the discontinuation of ART.

Short-course therapy with rifampin plus isoniazid, compared with standard therapy with isoniazid, for latent tuberculosis infection: a meta-analysis.

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 > or =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.

[Abnormal body fat distribution and type of antiretroviral therapy as predictors of cardiovascular disease risk in HIV-infected patients]. / Distribución anormal de la grasa corporal y tipo de tratamiento antirretroviral como predictores de riesgo de enfermedad cardiovascular en pacientes infectados por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: Dyslipidemia, insulin resistance and body fat redistribution are respectively short and long-term complications of protease inhibitor-containing antiretroviral regimens. To establish whether differences in the type of antiretroviral therapy (protease-containing or protease-sparing) or the presence and severity of body fat redistribution, explained differences in cardiovascular risk, we undertook a cross-sectional study. PATIENTS AND METHOD: The study was carried out in 219 consecutive HIV-infected patients attending an outpatient HIV clinic between February and April, 2002. Age, sex, smoking status, weight, height, waist circumference, blood pressure, antihypertensive treatment, total cholesterol, HDL cholesterol, triglycerides, and glucose concentrations, in addition to changes in body fat distribution were measured in 31 HIV-infected patients with no antiretroviral therapy, 35 HIV-infected patients treated with protease inhibitor-sparing regimens, and 153 HIV-infected patients treated with protease inhibitor-containing regimens. A ten-year cardiovascular disease risk was estimated according to the Framingham score. RESULTS: Patients treated with protease inhibitor-containing regimens as well as patients treated with protease inhibitor-sparing agents showed higher concentrations of cholesterol (p < 0.001), triglycerides (p = 0.004), glucose (p = 0.028), and greater changes in body fat distribution (p = 0.001) than patients with no antiretroviral therapy. An abnormal body fat distribution score was more strongly associated (p < 0.001) with the estimated 10-year cardiovascular disease risk than the type of HAART (p = 0.036). Ten-year cardiovascular disease risk increased linearly from 7.48% to 11.16% and to 19.50% in patients with no or mild, moderate and severe lipodystrophy scores, respectively. CONCLUSIONS: The results of this study encourage the use of cardiovascular preventive strategies in HIV-infected patients with severe lipodystrophy.

Once-a-day highly active antiretroviral therapy: a systematic review.

We analyzed the available evidence about the efficacy and tolerability of once-a-day highly active antiretroviral therapy (HAART), searching databases, conference proceedings, and journals. Two reviewers independently selected 6 uncontrolled and 2 randomized clinical trials of at least 24 weeks duration and with 80% participant follow-up. Regimens included didanosine (ddI), emtricitabine (FTC), and efavirenz (EFV) (2 studies, 326 patients); ddI, lamivudine (3TC), and EFV (3 studies, 147 patients); ddI, 3TC, EFV, and adefovir dipivoxil (1 study, 11 patients); ddI, nevirapine, and EFV (1 study, 15 patients); and ddI, 3TC, indinavir, and ritonavir (1 study, 10 patients). Virological efficacy ranged between 70% and 91%. Preliminary randomized clinical trials showed that once-a-day regimens (ddI, 3TC, and EFV or ddI, FTC, and EFV) had a virological efficacy at least similar to that of conventional HAART. The overall CD4 cell increase was at least 114 lymphocytes/microL. Tolerability was good, with a low discontinuation rate.