Effect of calcium-channel blockers on the risk of active tuberculosis and mortality: systematic review and meta-analysis.

Introduction: Recent studies suggest that calcium channel blockers (CCBs) could reduce the risk of active tuberculosis and improve clinical outcomes. We aimed to synthesize the evidence regarding the effect of CCBs on the risk of developing active tuberculosis and mortality. Methods: We systematically searched for observational studies and clinical trials published in six databases until 31 August 2023, following a PECO/PICO strategy. Results: We included eight observational studies, 4,020,830 patients, among whom 241,761 had diabetes mellitus and 30,397 had active tuberculosis. According to our results, CCBs reduce the risk of developing active tuberculosis by 29% (RR 0.71; 95% CI 0.67-0.75) in patients with and without diabetes mellitus. However, CCBs do not show any benefit in terms of tuberculosis-related mortality (RR 1.00; 95% CI 0.98-1.02). For both outcomes, no statistical heterogeneity was found (I2 = 0, p > 0.10). This protective effect of CCBs on the risk of active tuberculosis remained independent of the type of patient (with diabetes mellitus vs. general population) or the class of CCB administered (DHP-CCB vs. non-DHP-CCB) (test for subgroup differences I2 = 0, p > 0.10). However, this beneficial effect was more significant among the general population (RR 0.70; 95% CI 0.66-0.74) compared to patients with diabetes mellitus (RR 0.72; 95% CI 0.61-0.86) and among those patients treated with DHP-CCBs (RR 0.69; 95% CI 0.63-0.74) compared to patients treated with non-DHP-CCBs (RR 0.72; 95% CI 0.67-0.78). Conclusion: CCBs may reduce the risk of active TB in patients with diabetes and the general population. On the contrary, CCBs do not seem to have a protective effect on tuberculosis-related mortality. However, more evidence is still needed. We recommend developing clinical trials to verify these findings, including more diverse populations. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=352129].

High vs. low tidal volume and pulmonary complications in patients with cervical spinal cord injury on mechanical ventilation: systematic review.

Introduction: Cervical spinal cord injury (CSCI) patients on mechanical ventilation often lack standardized guidelines for optimal ventilatory support. This study reviews existing literature to compare outcomes between high tidal volume (HTV) and low tidal volume (LTV) strategies in this unique patient population. Methods: We searched for studies published up to August 30, 2023, in five databases, following a PECO/PICO strategy. We found six studies for quantitative analysis and meta-analyzed five studies. Results: This meta-analysis included 396 patients with CSCI and mechanical ventilation (MV), 119 patients treated with high tidal volume (HTV), and 277 with low tidal volume (LTV). This first meta-analysis incorporates the few studies that show contradictory findings. Our meta-analysis shows that there is no significant statistical difference in developing VAP between both comparison groups (HTV vs. LTV) (OR 0.46; 95% CI 0.13 to 1.66; p > 0.05; I2: 0%), nor are there differences between the presence of other pulmonary complications when treating with HTV such as acute respiratory distress syndrome (ARDS), atelectasis, onset of weaning. Conclusion: In patients with CSCI in MV, the use of HTV does not carry a greater risk of pneumonia compared to LTV; in turn, it is shown as a safe ventilatory strategy as it does not establish an increase in other pulmonary complications such as ARDS, atelectasis, the onset of weaning nor others associated with volutrauma. It is necessary to evaluate the role of HTV ventilation in this group of patients in primary RCT-type studies.

Conscious prone positioning in nonintubated COVID-19 patients with acute respiratory distress syndrome: systematic review and meta-analysis.

OBJECTIVE: To systematically review the effect of the prone position on endotracheal intubation and mortality in nonintubated COVID-19 patients with acute respiratory distress syndrome. METHODS: We registered the protocol (CRD42021286711) and searched for four databases and gray literature from inception to December 31, 2022. We included observational studies and clinical trials. There was no limit by date or the language of publication. We excluded case reports, case series, studies not available in full text, and those studies that included children < 18-years-old. RESULTS: We included ten observational studies, eight clinical trials, 3,969 patients, 1,120 endotracheal intubation events, and 843 deaths. All of the studies had a low risk of bias (Newcastle-Ottawa Scale and Risk of Bias 2 tools). We found that the conscious prone position decreased the odds of endotracheal intubation by 44% (OR 0.56; 95%CI 0.40 - 0.78) and mortality by 43% (OR 0.57; 95%CI 0.39 - 0.84) in nonintubated COVID-19 patients with acute respiratory distress syndrome. This protective effect on endotracheal intubation and mortality was more robust in those who spent > 8 hours/day in the conscious prone position (OR 0.43; 95%CI 0.26 - 0.72 and OR 0.38; 95%CI 0.24 - 0.60, respectively). The certainty of the evidence according to the GRADE criteria was moderate. CONCLUSION: The conscious prone position decreased the odds of endotracheal intubation and mortality, especially when patients spent over 8 hours/day in the conscious prone position and treatment in the intensive care unit. However, our results should be cautiously interpreted due to limitations in evaluating randomized clinical trials, nonrandomized clinical trials and observational studies. However, despite systematic reviews with meta-analyses of randomized clinical trials, we must keep in mind that these studies remain heterogeneous from a clinical and methodological point of view.

Prevalence of latent tuberculosis infection (LTBI) in healthcare workers in Latin America and the Caribbean: systematic review and meta-analysis.

Background: Tuberculosis remains a significant global health concern, and healthcare workers (HCWs) face a high risk of acquiring latent tuberculosis infection (LTBI) through occupational exposure. In the Latin American and Caribbean (LAC) region, where the burden of tuberculosis is substantial, understanding the prevalence of LTBI among HCWs is crucial for effective infection control measures. Therefore, we conducted a systematic review and meta-analysis to estimate the prevalence of LTBI among HCWs in LAC countries. Methods: Our search included MEDLINE, Scopus, EMBASE, Web of Science, and Google Scholar databases, focusing on relevant English-language records. We looked for observational studies from inception until December 2023. Results: Our analysis included 38 studies representing 15,236 HCWs and 6,728 LTBI cases. These studies spanned the period from 1994 to 2023 and were conducted in Brazil, Peru, Cuba, Colombia, Trinidad and Tobago, Mexico, and Chile. The mean prevalence of LTBI among HCWs was 35.32% (range 17.86-56.00%) for interferon-gamma release assay (IGRA) and 43.67% (range 6.68-70.29%) for tuberculin skin test (TST). The pooled prevalence of LTBI among HCWs was 34.5% (95% CI 25.4-44.1%) for IGRA and 43.0% (95% CI 35.5-50.7%) for TST. When considering both IGRA and TST tests, the overall prevalence of LTBI among HCWs was 40.98% (95% CI 34.77-47.33%). LTBI was associated with longer lengths of employment and exposure to patients, family members, or any person with TB. Additionally, older HCWs faced a higher risk of LTBI. Specific professional roles (such as nurses, nurse technicians, or physicians), smoking, and deficient TB infection control measures increased the likelihood of LTBI. However, information regarding gender and BCG vaccination status showed discordance among studies. Conclusion: Our findings underscore a substantial burden of LTBI among HCWs in LAC countries. Implementing adequate infection control measures is essential to prevent and control transmission within healthcare settings.

Testosterone levels and risk of newly diagnosed type 2 diabetes mellitus in adult men: systematic review and meta-analysis.

INTRODUCTION: Testosterone is a metabolically active hormone in males for metabolic homeostasis. Although the coexistence of low testosterone levels and type 2 diabetes mellitus (T2DM) have been associated, there are no reports that evaluate alterations in total testosterone (TT) levels and the risk of newly diagnosed T2DM. This review evaluates this question in adult men with high or low levels of total testosterone (TT), as well as the role played by other hormones such as free testosterone (FT), sex hormone binding globulin (SHBG), dihydrotestosterone (DHT), estrogens and testosterone bioavailable (bT). METHODS: We searched for studies published up to July 30, 2023, in five databases, following a PECO strategy. We found twenty-two studies for quantitative analysis and meta-analyzed the same quantity of studies. RESULTS: This first meta-analysis incorporates the assessment of the risk of low TT and T2DM in longitudinal studies. 43,038 adult men are included. Our meta-analysis shows that there is an association between low TT levels and the risk of newly diagnosed T2DM (OR 1.52; 95% CI 1.10-2.10; p < 0.05; I²: 79%). It is also evident that SHBG in low TT studies behaves as a risk factor for T2DM in the same way as FT, although without statistical significance. bT behaves as a protective factor. There is no association between estrogen, DHT and T2DM. CONCLUSIONS: In adult men with low TT values, there is a greater risk of developing a newly diagnosed of T2DM. SHBG values in low TT patients also present a higher risk of T2DM as the same FT but without statistical significance. bT behaves as a protective factor We have not found an association between risk of T2DM and the levels of estrogen, DHT although there are very few studies that report these hormones.

Association of beta blockers and mortality in adults with septic shock: systematic review and meta-analysis of randomized clinical trial.

Introduction: Septic shock still entails significant morbidity and mortality, with the heart being affected due to catecholamine overexpression and direct injury from sepsis. Therefore, the effect of ß-blocking the receptors to improve performance is promising when attempting to reverse tachycardia and reduce mortality. Methods: We conducted a comprehensive search across five databases for studies published up to 28 January 2024, using a PICO strategy. Ten studies were identified for quantitative analysis and included in our meta-analysis. Results: Our meta-analysis evaluated 28-day in-hospital mortality risk across nine randomized controlled trials (RCTs) involving a total of 1,121 adults with septic shock. We found an association between ß-blocker use and reduced overall mortality (OR 0.57; 95% CI 0.34-0.98; I 2: 56%). This effect was significant in the esmolol subgroup (OR 0.47; 95% CI 0.26-0.82; I 2: 32%), but not in the landiolol subgroup (OR 0.98; 95% CI 0.0-1,284.5; I 2: 72%). Additionally, the intervention group shows a significant reduction in HR and lactate levels, as well as an increase in stroke volume index (SVI). Conclusion: In adults with septic shock, ß-blockers are associated with a reduction in 28-day in-hospital mortality, a benefit primarily observed with esmolol rather than landiolol. Furthermore, improvements in heart rate (HR) control, lactate levels, and SVI were noted. However, these findings should be interpreted with caution, and further high-quality RCTs comparing different ß-blockers are necessary to better elucidate these effects. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024513610.

Droplet digital PCR vs. quantitative real time-PCR for diagnosis of pulmonary and extrapulmonary tuberculosis: systematic review and meta-analysis.

Tuberculosis is a rising global public health emergency. Then, it is a priority to undertake innovations in preventive, diagnostic, and therapeutic methods. Improved diagnostic methods for tuberculosis are urgently needed to address this global epidemic. These methods should be rapid, accurate, affordable, and able to detect drug-resistant tuberculosis. The benefits of these new diagnostic technics include earlier diagnosis and treatment, improved patient outcomes, and reduced economic burden. Therefore, we aimed to systematically review the diagnostic performance of droplet digital PCR (ddPCR)-a third-generation PCR-compared with quantitative Real Time-PCR (qPCR) for diagnosing pulmonary and extrapulmonary tuberculosis. We included 14 diagnostic accuracy test studies performed in Asia, Europe, and Latin America, 1,672 participants or biological samples, and 975 events (pulmonary or extrapulmonary tuberculosis). Most of the included studies had a low risk of bias (QUADAS-C tool). Sensitivity and specificity were lower for ddPCR [0.56 (95% CI 0.53-0.58) and 0.97 (95% CI 0.96-0.98), respectively] than for qPCR [0.66 (95% CI 0.60-0.71) and 0.98 (95% CI 0.97-0.99), respectively]. However, the area under the ROC curve (AUC) was higher for ddPCR than for qPCR (0.97 and 0.94, respectively). Comparing both AUCs using the Hanley & McNeil method, we found statistically significant differences (AUC difference of 4.40%, p = 0.0020). In the heterogeneity analysis, we found significant differences between both techniques according to the continent of origin of the study and the location of tuberculosis (pulmonary or extrapulmonary disease). The AUCs of both methods were similar in pulmonary tuberculosis. However, for extrapulmonary tuberculosis, the AUC was higher for ddPCR. We found some limitations: (1) significant heterogeneity of the studies, and (2) we could not perform subgroup analyses according to other relevant variables, such as the age and sex of the participants. Nonetheless, this study is the first meta-analysis that shows that ddPCR has a comparable diagnostic performance than qPCR for pulmonary tuberculosis. However, for extrapulmonary tuberculosis, ddPCR has a better discriminant capacity to differentiate between patients with and without extrapulmonary tuberculosis. We conclude that ddPCR is likely the best diagnostic technic for tuberculosis diagnosis, especially for extrapulmonary tuberculosis. More studies are still needed yet. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382768, CRD42022382768.

SGLT-2 inhibitors and prevention of contrast-induced nephropathy in patients with diabetes undergoing coronary angiography and percutaneous coronary interventions: systematic review and meta-analysis.

Introduction: SGLT2 inhibitors (SGLT2Is) have demonstrated cardioprotective and nephroprotective effects in patients with and without diabetes. Recent studies suggest that SGLT2Is may reduce the risk of contrast-induced nephropathy (CIN) in patients with diabetes undergoing coronary arteriography (CAG) or percutaneous coronary interventions (PCI). However, the evidence is still inconclusive. We aimed to systematically review the evidence regarding the potential nephroprotective role of SGLT2Is in preventing CIN in this population. Methods: We searched for studies in six databases published up to September 30, 2023, following a PECO/PICO strategy. Initially, we meta-analyzed five studies, but due to several reasons, mainly methodological concerns, we excluded one RCT. In our final meta-analysis, we included four observational studies. Results: This meta-analysis comprised 2,572 patients with diabetes undergoing CAG or PCI, 512 patients treated with SGLT2Is, and 289 events of CIN. This is the first meta-analysis demonstrating that SGLT2Is may reduce the risk of developing CIN by up to 63% (RR 0.37; 95% CI 0.24-0.58) in patients with diabetes undergoing CAG or PCI, compared to not using SGLT2Is. Statistical heterogeneity was not significant (I2 = 0%, p = 0.91). We assessed the certainty of the evidence of this systematic review and meta-analysis, according to the GRADE criteria, as moderate. Conclusion: SGLT2Is significantly reduce the risk of CIN by up to 63% in patients with diabetes undergoing CAG or PCI. Clinical trials are needed; several are already underway, which could confirm our findings and investigate other unresolved issues, such as the optimal dose, type, and duration of SGLT2 inhibitor therapy to prevent CIN. Systematic Review: PROSPERO, identifier CRD42023412892.

Acute Coronary Syndrome, Stroke, and Mortality after Community-Acquired Pneumonia: Systematic Review and Meta-Analysis.

One-third of adult inpatients with community-acquired pneumonia (CAP) develop acute coronary syndrome (ACS), stroke, heart failure (HF), arrhythmias, or die. The evidence linking CAP to cardiovascular disease (CVD) events is contradictory. We aimed to systematically review the role of CAP as a CVD risk factor. We registered the protocol (CRD42022352910) and searched for six databases from inception to 31 December 2022. We included 13 observational studies, 276,109 participants, 18,298 first ACS events, 12,421 first stroke events, 119 arrhythmic events, 75 episodes of new onset or worsening HF, 3379 deaths, and 218 incident CVD events. CAP increased the odds of ACS (OR 3.02; 95% CI 1.88-4.86), stroke (OR 2.88; 95% CI 2.09-3.96), mortality (OR 3.22; 95% CI 2.42-4.27), and all CVD events (OR 3.37; 95% CI 2.51-4.53). Heterogeneity was significant (I2 = 97%, p < 0.001). Subgroup analysis found differences according to the continent of origin of the study, the follow-up length, and the sample size (I2 > 40.0%, p < 0.10). CAP is a significant risk factor for all major CVD events including ACS, stroke, and mortality. However, these findings should be taken with caution due to the substantial heterogeneity and the possible publication bias.

Latent tuberculosis infection (LTBI) in health-care workers: a cross-sectional study at a northern Peruvian hospital.

Background: Healthcare workers (HCWs) have a higher risk of latent tuberculosis infection (LTBI) and active tuberculosis than the general population. In HCWs, the risk of tuberculosis infection depends on the local tuberculosis prevalence, HCWs' characteristics, the healthcare facility, and prevention and control measures. We aimed to estimate the prevalence and risk factors for LTBI in HCWs at a northern Peruvian hospital. Methods: This study had two phases: (1) a cross-sectional phase involving recruitment, history taking, and sampling for the Interferon-Gamma Release Assays (IGRA test), and (2) a prospective follow-up of IGRA-positive participants. We enrolled direct and non-direct patient caregivers among HCWs. We defined an LTBI case if the IGRA test was positive and clinical, laboratory, and radiological evaluations for active tuberculosis were negative. Results: We recruited 308 participants between November 2022 and May 2023. The mean age was 38.6 ± 8.3 years. Over 75% of the participants were female. The most common job category was technicians (30.5%), physicians (22.7%), nurses (20.5%), and other HCWs groups (17.5%). Most participants worked in hospital wards (28.2%), diagnostics departments (16.9%), and critical care departments (15.6%). The LTBI prevalence among HCWs was 17.86% (95% CI 13.84-22.70). In multivariate analysis, after adjusting for age, time working in our hospital, and family history of tuberculosis, males had a higher risk of LTBI (aPR 1.69, 95% CI 1.01-2.77) than females. Working for more than 10 years increased the risk of LBTI (aPR 2.4, 95% CI 1.44-3.97) compared to working for ≤10 years. Even further, participants who had worked for more than 20 years had an aPR of 4.31 (95% CI 1.09-13.65) compared to those with ≤10 years. Similarly, occupational exposure increased the risk of LTBI (aPR 2.21, 95% CI 1.27-4.08) compared to those HCWs not occupationally exposed. Conclusion: The LTBI prevalence in HCWs at a northern Peruvian hospital was lower compared to other Peruvian cities. Males, more experienced, and occupational exposed HCWs are at higher risk of LTBI. LTBI prevalence in Peruvian HCWs is still high. More studies are needed to address some aspects this study has not examined.

Effect of acute altitude exposure on physiological parameters and glucose metabolism in healthy lowland Peruvians.

BACKGROUND: High altitude exposure triggers a series of physiological changes to maintain homeostasis. Although longer-term (days to years) acclimatization processes are well studied, less is known about the physiological changes upon rapid ascent. We took advantage of Peru's geography to measure the first physiological changes following rapid transport from a low to a high-altitude environment among lowlanders. METHODS: Blood glucose, insulin, C-peptide, and salivary cortisol among healthy lowland Peruvians were measured before and after glucose ingestion at 40 m and upon arrival at 3470 m. Resting heart rate, blood oxygen saturation, and blood pressure were also monitored. RESULTS: At high altitude, we find a significant ( p<0.05) increase in heart rate and a decrease in blood oxygen saturation and salivary cortisol. Additionally, baseline levels of blood glucose, plasma C-peptide, and cortisol were reduced ( p<0.05). Blood glucose, plasma insulin, and plasma C-peptide returned to baseline or below faster at high altitude after glucose ingestion. CONCLUSIONS: Although many overlapping environmental and physiological factors are present in the high-altitude environment, the first steps of acclimatization in this population appear to be caused by increased energy expenditure and glucose metabolism to maintain oxygen homeostasis until the longer-term acclimatization mechanisms become more significant.

Impact of the COVID-19 pandemic on the incidence and clinical outcomes of diabetic ketoacidosis among male and female children with type 1 diabetes: systematic review and meta-analysis.

Background: Some studies suggest that the SARS-CoV-2 pandemic increased the incidence of type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis (DKA). However, the impact of this pandemic on pediatric T1DM is still mostly unknown. Therefore, we aimed to assess the effect of the COVID-19 pandemic on clinical outcomes in children with T1DM. Methods: We systematically searched for six databases up to 31 August 2022. We included 46 observational studies, 159,505 children of both sexes with T1DM, and 17,547 DKA events. Results: The COVID-19 pandemic significantly increased, in both sexes, the incidence of 1) DKA (OR 1.68; 95% CI 1.44-1.96), 2) severe DKA (OR 1.84; 95% CI 1.59-2.12), 3) DKA in newly diagnosed T1DM (OR 1.75; 95% CI 1.51-2.03), and 4) ICU admissions (OR 1.90; 95% CI 1.60-2.26). However, we did not find a significant association between this pandemic and 1) the incidence of T1DM, 2) the incidence of DKA in established T1DM, 3) the incidence of KDA complications, 4) the length of hospitalization stay, and 5) mortality. Subgroup analysis showed that the study design and the continent of origin accounted for the heterogeneity. Conclusions: The pandemic SARS-CoV-2 raised, in both sexes, the risk of DKA, severe DKA, DKA de novo, and ICU admissions.

Effect of Oral Antidiabetic Drugs on Tuberculosis Risk and Treatment Outcomes: Systematic Review and Meta-Analysis.

Tuberculosis and diabetes mellitus are two global pandemics and rising public health problems. Recent studies suggest that oral antidiabetic drugs (OADs) could reduce the risk of tuberculosis and improve clinical outcomes. However, the evidence is controversial. Therefore, we aimed to assess the effect of OADs on the risk of tuberculosis and treatment outcomes. We systematically searched for six databases from inception to 31 August 2022. We followed a predefined PICO/PECO strategy and included two randomized controlled trials and sixteen observational studies. This study collects 1,109,660 participants, 908,211 diabetic patients, and at least 13,841 tuberculosis cases. Our results show that metformin decreases the risk of active tuberculosis by 40% (RR 0.60; 95% CI 0.47-0.77) in diabetic patients. In addition, metformin exhibits a dose-response gradient (medium doses reduce the risk of active tuberculosis by 45%, while high doses reduce this risk by 52%). On the other hand, DPP IV inhibitors increase the risk of active tuberculosis by 43% (RR 1.43; 95% CI 1.02-2.02). Subgroup analysis showed that study design and metformin dose accounted for the heterogeneity. We conclude that metformin significantly protects against active tuberculosis among diabetic patients. On the contrary, DPP IV inhibitors could increase the risk of developing active tuberculosis.

Tetanus secondary to oral and odontogenic infections: a case report and systematic literature review.

Objectives: Tetanus is a potentially lethal infection and remains a priority public health problem in countries with low vaccination coverage. We aim to synthesize the evidence on the clinical-epidemiologic characteristics of oral (odontogenic) tetanus. Methods: We report a case of oral tetanus. Furthermore, we collected eligible articles about oral tetanus published to date. We performed a systematic review with an exhaustive search of the literature published up to June 30, 2022, in Medline (PubMed), Google Scholar, Scopus, EMBASE, Web of Science, and ScienceDirect. Results: We analyzed 19 studies that enrolled 26 cases of oral tetanus. The mean age was 51.60 ± 21.95 (range 10-77) years. The frequency and lethality of odontogenic tetanus were higher in males than females. More than 60% of cases occurred in North America. Almost three-quarters of cases were associated with a dental procedure - mainly dental extraction - meanwhile, tooth decay accounted for 23% of cases. The median incubation period was 8.0 (IQR 10.0) days. The time between trismus and death was 4.25±1.89 (range 3-7) days. Clostridium tetani was isolated in only 11.54% of cases. Administration of anti-tetanus immunoglobulin alone or combined with anti-tetanus toxoid was reported in at least 42% of cases, and antibiotics in 32% of cases. Patients required tracheostomy and mechanical ventilation in 12% and 8% of cases, respectively. The mean hospital stay was 18.38±14.97 (range 4-53) days. The lethality of odontogenic tetanus was (30.77%). Conclusion: Since the diagnosis of tetanus is merely clinical, it is crucial to have a high index of suspicion to diagnose this disease correctly. Although odontogenic tetanus is rare, it is potentially life-threatening.

Further insights into to the role of statins against active tuberculosis: systematic review and meta-analysis.

Objectives: Tuberculosis is a major cause of global morbidity and mortality. Statins could be associated with a lower risk of some infectious diseases, including tuberculosis. Statins could reduce the risk of latent tuberculosis infection and active tuberculosis, acting as an adjuvant in treating tuberculosis. This study aimed to determine if statins reduce the risk of active tuberculosis. Methods: We systematically analyzed 8 databases from inception to December 2021. We included articles without language restriction if they met our inclusion and exclusion criteria and the PECO strategy (Population: adults without active pulmonary tuberculosis; Exposure: treatment with any statin; Comparator: no use of statins; Outcome: active tuberculosis). Odds Ratios (ORs) with 95% confidence intervals (CIs) were pooled using random- effects models regardless of heterogeneity quantified by Cochran's Q and I2 statistics. We performed subgroup analyses according to the participants' diabetic status and follow-up length (≤10 years or >10 years). Results: Twelve articles reporting observational studies involving 3.038.043 participants, including at least 32.668 cases of active tuberculosis. Eight reported retrospective cohort studies, three nested case-control study, and one was a case control study.According to our meta-analysis, statins may reduce the risk of active tuberculosis, in the general population (OR 0.66; 95% CI, 0.54-0.81), in non-diabetic (OR 0.66; 95% CI, 0.54-0.80) and in diabetic patients (OR 0.65; 95% CI, 0.49-0.87). This protective effect did not differ according to the participants' diabetic status nor follow-up length (test for subgroup differences I2=0). We found significant clinical and methodological heterogeneity. Similarly, the forest plot, and the I2 and Chi2 statistics suggested considerable statistical heterogeneity (I2=95%, p<0.05, respectively). Of the 12 included studies, 9 were at low risk of bias and 3 were at high risk of bias. Similarly, according to the funnel plot, it is very likely that there are important publication biases. Conclusion: Statin use may significantly reduce the risk of tuberculosis in the general population, diabetic and non-diabetic patients. Nevertheless, caution should be exercised when interpreting these conclusions, due to the quality of the evidence, the heterogeneity of the studies, the presence of bias, and the difficulty in extrapolating these results to populations of other races and ethnicities.

Periodontal disease as a non-traditional risk factor for acute coronary syndrome: a systematic review and meta-analysis.

Objectives: Previous observational studies have suggested an association between periodontal disease (PD) and cardiovascular and cerebrovascular diseases. Nonetheless, evidence linking PD with coronary heart disease (CHD) and acute coronary syndrome (ACS) is still contradictory. We aim to systematically review the role of PD as a risk factor for ACS (myocardial infarction and unstable angina). Methods: The protocol was registered in PROSPERO (CRD42021286278) and we followed the recommendations of the PRISMA and AMSTAR 2 guidelines. We systematically searched for 7 databases and electronic thesis repositories from inception to February 2022. We included articles without language restriction following the PECO strategy (population: "adult participants"; exposure: "periodontal disease"; comparator: "no periodontal disease"; outcome: "acute coronary syndrome" OR "acute myocardial infarction" OR "unstable angina"). Odds ratios (OR) with 95% confidence intervals (95% CI) were pooled using random effects and heterogeneity was quantified by Cochran's Q and Higgins' I2 statistics. Subgroup analyses were carried out according to the participants' sex, type of diagnosis of PD, type of study, and continent of origin of studies. Results: We included 46 papers (17 cohort, 25 case-control, and 4 cross-sectional studies) that met the inclusion criteria. This meta-analysis includes a total of 6,806,286 participants and at least 68,932 ACS events, mainly myocardial infarction (MI). In accordance with our results, PD is associated with a higher risk of ACS (OR 1.35; 95% CI 1.25-1.45). However, clinical and methodological heterogeneity was significant (I2=86%, p<0.05). In the sensitivity analysis, the exclusion of some studies with "extreme" results (outliers) did not significantly affect the overall estimate or heterogeneity. In subgroup analysis, we found no statistically significant differences between men and women according to subgroup difference tests (I2=0%, p=0.67). Conversely, there were differences according to the type of diagnosis of PD (clinical or self-reported diagnosis), type of study (cohort, case-control, or cross-sectional study), and the continent of origin (North America, South America, Asia, or Europe) of the studies (I2=79%-96%, p<0.10). Of the 46 studies, only 4 had a high risk of bias. Additionally, the funnel plot suggested publication bias. Conclusion: PD may be an important non-traditional risk factor for ACS. Although, this meta-analysis brings together more studies, and therefore more evidence, than any other previous similar study, its results should be interpreted with caution due to the great heterogeneity and the potential presence of bias.

Conscious prone positioning in nonintubated COVID-19 patients with acute respiratory distress syndrome: systematic review and meta-analysis / Pronação consciente em pacientes com COVID-19 não intubados e com síndrome do desconforto respiratório agudo: revisão sistemática e metanálise

ABSTRACT Objective: To systematically review the effect of the prone position on endotracheal intubation and mortality in nonintubated COVID-19 patients with acute respiratory distress syndrome. Methods: We registered the protocol (CRD42021286711) and searched for four databases and gray literature from inception to December 31, 2022. We included observational studies and clinical trials. There was no limit by date or the language of publication. We excluded case reports, case series, studies not available in full text, and those studies that included children < 18-years-old. Results: We included ten observational studies, eight clinical trials, 3,969 patients, 1,120 endotracheal intubation events, and 843 deaths. All of the studies had a low risk of bias (Newcastle-Ottawa Scale and Risk of Bias 2 tools). We found that the conscious prone position decreased the odds of endotracheal intubation by 44% (OR 0.56; 95%CI 0.40 - 0.78) and mortality by 43% (OR 0.57; 95%CI 0.39 - 0.84) in nonintubated COVID-19 patients with acute respiratory distress syndrome. This protective effect on endotracheal intubation and mortality was more robust in those who spent > 8 hours/day in the conscious prone position (OR 0.43; 95%CI 0.26 - 0.72 and OR 0.38; 95%CI 0.24 - 0.60, respectively). The certainty of the evidence according to the GRADE criteria was moderate. Conclusion: The conscious prone position decreased the odds of endotracheal intubation and mortality, especially when patients spent over 8 hours/day in the conscious prone position and treatment in the intensive care unit. However, our results should be cautiously interpreted due to limitations in evaluating randomized clinical trials, nonrandomized clinical trials and observational studies. However, despite systematic reviews with meta-analyses of randomized clinical trials, we must keep in mind that these studies remain heterogeneous from a clinical and methodological point of view.

RESUMO Objetivo: Revisar sistematicamente o efeito da posição prona na intubação endotraqueal e na mortalidade em pacientes com COVID-19 não intubados com síndrome do desconforto respiratório agudo. Métodos: Registramos o protocolo (CRD42021286711) e pesquisamos quatro bancos de dados e literatura cinzenta desde o início até 31 de dezembro de 2022. Incluímos estudos observacionais e ensaios clínicos. Não houve limite de data ou idioma de publicação. Excluímos relatos de casos, séries de casos, estudos não disponíveis em texto completo e estudos que incluíram pacientes < 18 anos de idade. Resultados: Incluímos 10 estudos observacionais, 8 ensaios clínicos, 3.969 pacientes, 1.120 eventos de intubação endotraqueal e 843 mortes. Todos os estudos tinham baixo risco de viés (ferramentas Newcastle-Ottawa Scale e Risk of Bias 2). Observamos que a pronação consciente reduziu as chances de intubação endotraqueal em 44% (RC 0,56; IC95% 0,40 - 0,78) e a mortalidade em 43% (RC 0,57; IC95% 0,39 - 0,84) em pacientes com COVID-19 não intubados com síndrome do desconforto respiratório agudo. Esse efeito protetor sobre a intubação endotraqueal e a mortalidade foi mais robusto naqueles que passaram > 8 horas por dia na pronação consciente (RC 0,43; IC95% 0,26 - 0,72 e OR 0,38; IC95% 0,24 - 0,60, respectivamente). A certeza da evidência, de acordo com os critérios GRADE, foi moderada. Conclusão: A pronação consciente diminuiu as chances de intubação endotraqueal e mortalidade, especialmente quando os pacientes passaram > 8 horas por dia na pronação consciente e tratamento na unidade de terapia intensiva. Contudo, nossos resultados devem ser interpretados com cautela devido às limitações na avaliação de ensaios clínicos randomizados, ensaios clínicos não randomizados e estudos observacionais. Não obstante, apesar das revisões sistemáticas com metanálises de ensaios clínicos randomizados, devemos ter em mente que esses estudos permanecem heterogêneos do ponto de vista clínico e metodológico.

Puntaje APP como predictor de mortalidad en pacientes con síndrome de dificultad respiratoria agudo grave por COVID-19 en un hospital referencial del norte del Perú / APP score as a predictor of mortality in patients with severe acute respiratory distress syndrome due to COVID-19 in a reference hospital in northern of Peru

INTRODUCCIÓN: La mortalidad por pacientes por COVID-19 grave que desarrollaban neumonía grave y síndrome de dificultad respiratoria agudo (SDRA) grave ha sido significativa a pesar del tratamiento oportuno. Es importante determinar predictores tempranos de enfermedad que nos ayuden a estratificar aquellos pacientes con mayor riesgo de fallecer. Se pretende estudiar el comportamiento del puntaje APP (APPS) como predictor de ello, basados en algunos reportes de uso y utilidad en el SDRA. no COVID-19. OBJETIVO: Determinar si el APPS es útil como predictor de mortalidad en SDRA. por COVID-19 grave. PACIENTES Y MÉTODO: Se realizó un estudio tipo cohorte retrospectivo, incluyendo pacientes de la Unidad de Cuidados Intensivos (UCI), con SDRA. por COVID-19 grave, que ingresaron a la UCI del Hospital Regional Docente de Trujillo (HRDT) en el período abril 2020- abril 2021. Se evalúo la utilidad del APPS como predictor de mortalidad em dicha población. RESULTADOS: El APPS demostró ser un factor asociado a mortalidad en pacientes con SDRA. y COVID-19 grave (RPa 1,34; IC 95% 1,16 a 1,56; p < 0,001). Además, encontramos que, al realizar un modelo de predicción ajustado por edad, sexo, SOFA, APPS, shock, Indice de Charlson (ICh), se comportan como factores asociados a mortalidad el APPS, el sexo masculino (RPa: 1,48; IC 95% 1,09 a 2,049; p < 0,05) y el ICh (RPa: 1,11; IC 95% 1,02 a 1,21; p < 0,05). CONCLUSIÓN: El APPS, el sexo masculino y el ICh son predictores de mortalidad en SDRA. por COVID-19 grave.

BACKGROUND: Mortality in patients with severe COVID-19 who developed severe pneumonia and severe Acute Respiratory Distress Syndrome (ARDS) has been significant despite timely treatment. It is important to determine early predictors of disease that help us to stratify those patients with a higher risk of death. It is intended to study the behavior of the APPS score as a predictor of this, based on some reports of use and usefulness in non-COVID-19 ARDS. AIM: To determine if the APP score is useful as a predictor of mortality in ARDS due to severe COVID-19. METHOD: A retrospective cohort study was carried out, including patients from the Intensive Care Unit (ICU) with ARDS due to severe COVID-19 who were admitted to the ICU of the Trujillo Regional Teaching Hospital (HRDT) in the period March 2020 to March 2021. The usefulness of the APP score as a predictor of mortality in mentioned population was evaluated. RESULTS: The APP score proved to be a factor associated with mortality in patients with ARDS and severe COVID-19 (APR 1.34; 95% CI 1.16 to 1.56; p < 0.001). We also found that when performing a prediction model adjusted for age, sex, SOFA, APP score, shock and Charlson Index (ICh) we found that the APP score, male sex (APR: 1.48; 95% CI 1.09 to 2.049; p < 0.05) and the ICh behave as factors associated with mortality (RPa: 1.11; 95% CI 1.02 to 1.21; p < 0.05). CONCLUSION: The APP score, male sex, and ICh are predictors of mortality in ARDS due to severe COVID-19.

Eficacia de tenecteplase comparada con alteplase para tratamiento de ictus isquémico agudo. Una revisión narrativa

Introducción: La trombólisis intravenosa con Alteplase (ALT) se recomienda como tratamiento estándar siendo el único agente trombolítico aprobado por la FDA, en infarto cerebral. La Tenecteplase (TNK), un activador tisular del plasminógeno modificado, surge como agente antitrombótico alternativo. Esta revisión narrativa evalúa la evidencia actual y aborda los problemas prácticos sobre la eficacia y seguridad de tenecteplase en comparación con alteplase. Metodología: Se realizó una búsqueda sistemática y analítica de la literatura, y se proporcionó una síntesis cualitativa de metaanálisis y ensayos clínicos concluidos, que compararon la efectividad y seguridad de la tenecteplase con alteplase en el AIS, utilizando artículos indexados en MEDLINE, Cochrane Library y Scopus. Resultados: Los ensayos clínicos aleatorizados en su mayoría coinciden al encontrar que TNK es al menos tan o más efectiva que la ALT para mejoría neurológica después del AIS; mientras los metaanálisis coinciden en que los pacientes que recibieron TNK presentaron una mayor recanalización exitosa, pero difieren en cuanto a los hallazgos de mejoría neurológica temprana, resultado funcional a los 90 días y mortalidad a los 90 días. Conclusión: La tenecteplase es al menos tan eficaz como la Alteplase con respecto a la mejoría neurológica después del tratamiento del accidente cerebrovascular isquémico agudo.

Introduction: Intravenous thrombolysis with alteplase (ALT) is recommended as standard treatment, being the only thrombolytic agent approved by the FDA. Tenecteplase (TNK), a modified tissue plasminogen activator, is emerging as an alternative antithrombotic agent. This narrative review assesses the current evidence and addresses practical issues regarding the efficacy and safety of tenecteplase compared to alteplase. Methodology: A systematic and analytical search of the literature was performed, providing a qualitative synthesis of meta-analyses and completed clinical trials comparing the effectiveness and safety of tenecteplase with alteplase in AIS, using articles indexed in MEDLINE, the Cochrane Library, and Scopus. Results: Randomized clinical trials mostly agree in finding TNK to be at least as or more effective than ALT for neurological improvement after AIS; while the meta-analyses agree that patients who received TNK had more successful recanalization, they differ in terms of the findings of early neurological improvement, functional outcome at 90 days, and mortality at 90 days. Conclusion: Tenecteplase is at least as effective as alteplase with regard to neurological improvement after treatment of acute ischemic stroke.