Consensus Guidelines for Influenza Vaccination in Patients with Diabetes.

Influenza is a prevalent health issue encountered in daily practice. Patients with diabetes mellitus face a higher risk of infections, including influenza, owing to the compromised immune system associated with diabetes. This susceptibility arises from the potential of diabetes mellitus to weaken the immune system. Moreover, elevated blood glucose levels can create a conducive environment for the growth of bacteria and viruses. This consensus is formulated by a multidisciplinary team to serve as practical guidance for the administration of influenza vaccinations to patients with diabetes mellitus in daily practice.

Different doses of imeglimin for management of type 2 diabetes mellitus: a systematic review, meta-analysis, and meta-regression of randomized clinical trials.

BACKGROUND: A new medication for type 2 diabetes mellitus (T2DM) called imeglimin can target all three organs involved in the pathogenesis of DM, namely the liver, skeletal muscles, and pancreas. This research seeks to examine the most efficacious and safe dose of imeglimin for the management of T2DM. RESEARCH DESIGN AND METHODS: Using particular keywords, we searched the CENTRAL, Medline, Scopus, and ClinicalTrials.gov databases for pertinent literature. The results of continuous variables were pooled into the mean difference (MD) and dichotomous variables into odds ratio (OR) along with their 95% confidence intervals (95% CI) using fixed-effect models. RESULTS: Our pooled analysis revealed that imeglimin 1000 mg twice daily [MD -0.90% p < 0.00001] and 1500 mg twice daily [MD -0.84% p = 0.0003] as monotherapy was associated with a higher reduction in the HbA1c compared to placebo. This superiority was still maintained when given as combination therapy. Regrettably, there was an observed escalation in gastrointestinal AEs as the dosage of imeglimin was raised, despite the absence of a corresponding improvement in its efficacy in decreasing HbA1c levels. CONCLUSIONS: Our study suggests that imeglimin 1000 mg twice daily may offer the most optimum therapeutic effects for glycemic control without compromising its safety profiles.

Anti-SARS-CoV-2 Antibody Level Is Associated with a History of COVID-19 Infection and mRNA Vaccination in Patients with Diabetes.

Type 2 diabetes mellitus (T2DM) is associated with higher severity and mortality in SARS-CoV-2 infections. Vaccination has been encouraged to boost immunity and prevent these unfortunate outcomes. Few studies have evaluated antibody levels after COVID-19 vaccination in patients with T2DM. Therefore, we examined the vaccination status and anti-SARS-CoV-2 antibody levels to identify the factors that affect the antibody levels in patients with T2DM. This cross-sectional study was conducted at the Dr. Hasan Sadikin Hospital and Bandung Kiwari Hospital, Bandung, West Java, Indonesia, between October and November 2022. Adult participants with and without T2DM were tested for SARS-CoV-2 antibodies using a point-of-care quantitative immunochromatographic assay. We enrolled 289 participants: 201 participants with T2DM and 88 participants without T2DM. The T2DM participants had a lower vaccination rate compared with the non-T2DM participants. However, no significant differences in antibody levels were observed between the two groups. Higher antibody levels among the T2DM participants were associated with mRNA vaccination and a history of COVID-19 illness. The lower antibody response observed among the T2DM participants with chronic obstructive pulmonary disease suggests that such patients may need antibody level measurement and an additional booster vaccine.

The effect of diabetes mellitus on COVID-19 mortality among patients in a tertiary-level hospital in Bandung, Indonesia.

Immune system dysregulation in people with diabetes mellitus (DM) increases the risk of acquiring severe infection. We compared the clinical characteristics and laboratory parameters of coronavirus disease 2019 (COVID-19) patients with and without DM and estimated the effect of DM on mortality among COVID-19 patients. A retrospective cohort study collecting patients' demographic, clinical characteristics, laboratory parameters and treatment outcomes from medical records was conducted in a hospital in Bandung City from March to December 2020. Univariable and multivariable logistic regression was performed to determine the association between DM and death. A total of 664 COVID-19 patients with positive real-time reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 were included in this study, of whom 147 were with DM. Half of DM patients presented HbA1c ≥10%. DM patients were more likely to present with comorbidities and severe to critical conditions at admission (P <0.001). Laboratory parameters such as neutrophil-lymphocyte count ratio, C-reactive protein, D-dimer, ferritin, and lactate dehydrogenase were higher in the DM group. In the univariate analysis, variables associated with death were COVID-19 severity at baseline, neurologic disease, DM, age ≥60 years, hypertension, cardiovascular disease, and chronic kidney disease. DM remained associated with death (aOR 1.82; 95% CI 1.13-2.93) after adjustment with sex, age, hypertension, cardiovascular disease, and chronic kidney disease. In conclusion, COVID-19 patients with DM are more likely to present with a very high HbA1c, comorbidities, and severe-critical illness. Chronic inflammation in DM patients may be aggravated by the disruption of immune response caused by COVID-19, leading to worse laboratory results and poor outcomes.

The association between metabolic dysfunction-associated fatty liver disease and chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The term metabolic dysfunction-associated fatty liver disease (MAFLD) has been established to better define patients with fatty liver disease who also present with metabolic dysfunction. However, the association between MAFLD and chronic-kidney disease (CKD) remains elusive. METHODS: . We conducted systematic literature searching across multiple databases-PubMed, EMBASE, Cochrane library, and Google Scholar up until June 9th, 2022. The main exposure was the diagnosis of MAFLD and nonalcoholic fatty liver disease (NAFLD) regardless of the diagnostic modalities being used. The outcome of interest was the prevalence or the incidence of CKD. RESULTS: There were 355,886 subjects from 11 included studies with the period of follow up of 4.6-6.5 years. Meta-analysis of cross-sectional studies showed that MAFLD was associated with a higher prevalent CKD (OR 1.50, 95%CI [1.02-2.23]; test for overall effect Z = 2.04, p = 0.04; I2 = 97.7%, p < 0.001) and incident CKD (adjusted HR 1.35, 95%CI [1.18-1.52]; test for overall effect Z = 15.47, p < 0.001; I2 = 84.6%, p < 0.001) and did not vary between age, sex, comorbidities, study region, and follow-up duration. No difference in CKD prevalence was found between MAFLD and NAFLD patients. Significant liver fibrosis, but not steatosis in was associated with greater odds of developing CKD. More severe MAFLD was also associated with higher odds of developing CKD. CONCLUSION: This present meta-analysis using a large population indicates a significant association between MAFLD and the prevalence and incidence of CKD.

Diabetes and Mortality among Patients with Chronic Kidney Disease and COVID-19: A Systematic Review, Meta-analysis, and Meta-regression.

Introduction: Patients with kidney disease and COVID-19, whether on hemodialysis (HD) or not, have a higher risk of contracting COVID-19 accompanied by a higher mortality rate due to suppressed immune functions. Diabetes, one of the ubiquitous etiology of kidney disease, is also associated with a composite of poor outcomes. Methods: Meta-analysis and meta-regression of 13 articles on COVID-19 patients with chronic kidney disease, with information on diabetes and mortality were performed using Review Manager 5.4 and OpenMetaAnalyst. Results: The meta-analysis of a pooled subject of 18,822 patients showed that the presence of diabetes in CKD patients with COVID-19 was associated with an increased risk of mortality (RR 1.41 (1.15, 1.72); P < 0.001; I2 70%, P < 0.001). Subgroup analysis showed that diabetes was not associated with mortality in the HD group (RR 1.27 (1.06, 1.54); P = 0.01; I2 0%, P = 0.70) but showed a significant association in the non-HD group (RR 1.66 (1.59, 1.73); P < 0.001; I2 85%, P < 0.001). Male gender (P = 0.070) contributed to the effect size differences (age: P < 0.001; hypertension: P = 0.007; CVD: P < 0.001; lung disease: P < 0.001). Conclusions: Diabetes was associated with higher mortality risk among CKD patients, primarily those who did not need RRT.

Empirical Antibiotic for Diabetic Foot Infection in Indonesian Tertiary Hospital, Is It Time to Rethink the Options?

BACKGROUND: The choice of empiric antibiotics in Diabetic Foot Infection (DFI) is a key to successful therapy. Meanwhile, the management of DFI in Indonesia is  based on guideline originating from western countries which have different bacteriological patterns. Therefore, this study aimed to describe the bacterial and antibiotic susceptibility pattern on DFI which potentially contribute to better antibiotics selection guidelines. METHODS: This was a cross-sectional descriptive study conducted using consecutive sampling with DFI patients admitted in the emergency room and wards of Hasan Sadikin Hospital between February and July 2020. Tissue samples were obtained from all wounds, while antibiotic susceptibility tests were carried out on the culture results. RESULTS: A total of 65 bacterial growths were obtained from 45 enrolled patients. Gram-negative bacteria dominated with 54 growths (83.07%) including Klebsiela pneumonia 13 (20%) as the most common. Furthermore, antibiotics with good susceptible (> 80%) against Gram-negative bacteria are the carbapenemes (meropenem and ertapenem) and amikacin. The multi drug resistant bacteria were found in 18 growths (27.7%), which include ESBL, Carbapenemase producing bacteria, and MRSA. However, there were no susceptibility pattern differences between patients with ulcer duration above or below 2 months, higher grade wound (Wagner 4 and 5) and lower, as well as patients with previous or no antibiotic history. CONCLUSION: The growth of Gram-negative bacteria dominated DFI with limited susceptibility to the empirical first-line antibiotics in the known international guidelines. Therefore, there is a need to reconsider the algorithm for selecting empirical antibiotics and management of DFI which is appropriate in our current condition.

The prognostic values of thyroid disorders in predicting COVID-19 composite poor outcomes: A systematic review and meta-analysis.

BACKGROUND AND AIMS: In this meta-analysis, we aimed to evaluate the prognostic properties of thyroid disorder during admission on poor prognosis and factors that may influence the relationship in patients with COVID-19. METHODS: A systematic literature search of PubMed, EBSCO, and CENTRAL was conducted from inception to August 27, 2021. The main exposure was unspecified and specified thyroid disorders-hypothyroidism or hypothyroidism. The outcome of interest was the COVID-19 composite poor outcome that comprises of severity, mortality, ICU admission, and hospitalization. RESULTS: There were 24,734 patients from 20 studies. Meta-analysis showed that thyroid disorder was associated with composite poor outcome (OR 2.87 (95% CI 2.04-4.04), p < 0.001; I2 = 62.4%, p < 0.001). Meta regression showed that age (p = 0.047) and hypertension (p = 0.01), but not gender (p = 0.15), DM (p = 0.10), CAD/CVD (p = 0.38), obesity (p = 0.84), and COPD (p = 0.07) affected the association. Subgroup analysis showed that thyroid disorder increased risk of severe COVID-19 (OR 5.13 (95% CI 3.22-8.17), p < 0.05; I2 = 0%, p = 0.70) and mortality (OR 2.78 (95%CI 1.31-5.90), p < 0.05; I2 = 80%, p < 0.01). Pooled diagnostic analysis of thyroid disorder yielded a sensitivity of 0.22 (0.13-0.35), specificity of 0.92 (0.87-0.95), and AUC of 0.72. The probability of poor outcome was 38% in patients with thyroid disorder and 15% in patients without thyroid abnormality. CONCLUSION: On-admission thyroid disorder was associated with poor prognosis in COVID-19 patients.

Antibody response following SARS-CoV-2 vaccination among patients with type 2 diabetes mellitus: A systematic review.

BACKGROUND AND AIM: DM patients' antibody response after the COVID-19 vaccine is still unknown amid the COVID-19 vaccination rollout. This study aimed to explore the SARS-CoV-2 antibody response or seropositivity among DM patients following the COVID-19 vaccine administration. METHODS: We performed a systematic review of the literature consisting of observational or cross-sectional studies, which reported the antibody serology or seropositivity among DM patients by following the PRISMA 2020 guidelines. RESULTS: Eight studies with a total of 64468 patients were identified, and 5156 (7.9%) of them had diabetes. Most studies showed that antibody response and seropositivity in DM patients were lower than healthy population after one until four weeks following full COVID-19 vaccination dose. CONCLUSION: The antibody response and seropositivity after the COVID-19 vaccine in DM patients were lower than in healthy subjects. Therefore, DM patients are expected to receive vaccines according to the dose and schedule appropriately and might be prioritized to receive vaccine boosters.

The Prognostic Properties of Thyroid Disorders, Hypothyroidism, and Hyperthyroidism in Predicting COVID-19 Poor Outcomes: A Systematic Review and Diagnostic Meta-analysis.

Purpose: The relationship between thyroid metabolism and coronavirus disease 2019 (COVID-19) inflammation has been extensively investigated. This meta-analysis aimed to evaluate the prognostic properties of unspecified thyroid disorders, hypothyroidism and hyperthyroidism for predicting poor COVID-19 outcomes. Methods: We conducted systematic literature searching through multiple databases-PubMed, EBSCO and CENTRAL up until 27 September 2021. The main exposure was unspecified thyroid disorders, hypothyroidism or hypothyroidism on-admission status. The outcome of interest was the COVID-19 composite poor outcome that comprises severity, mortality, ICU admission and hospitalisation. Results: There were 24517 patients from 20 studies. Meta-analysis showed that thyroid disorder, regardless of its type, was associated with COVID-19 poor outcome (OR 2.92 (95% CI 2.09 - 4.08), P < 0.001; I2 = 71%, P < 0.001). Unspecified thyroid disorder has a sensitivity of 0.17 (0.08-0.33), specificity of 0.94 (0.88-0.97) and Area Under Curve (AUC) of 0.66. Hypothyroidism has a sensitivity of 0.24 (0.12-0.42), specificity of 0.92 (0.87-0.96) and AUC of 0.77. Hyperthyroidism has a sensitivity of 0.05 (0.02-0.11), specificity of 0.98 (0.88-1.00) and AUC of 0.36. In this pooled analysis, the posttest probability of unspecified thyroid disease, hypothyroidism and hyperthyroidism were 42%, 27% and 8% for poor outcomes, respectively. Conclusion: Thyroid disorders are associated with poor COVID-19 prognosis.

Prognostic properties of hypoalbuminemia in COVID-19 patients: A systematic review and diagnostic meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) elicits robust inflammatory reaction that may result in a declining albumin serum level. This meta-analysis aimed to evaluate the prognostic properties of hypoalbuminemia for poor prognosis and factors that may influence the relationship. METHOD: A systematic literature search of PubMed was conducted from inception to April 22, 2021. The main exposure was albumin level below normal range-defined by the included studies. The outcome of interest was composite poor outcome that comprises of mortality, severity, and the requirement of mechanical ventilation or intensive care unit. RESULTS: There were 6200 patients from 19 studies. Meta-analysis showed that hypoalbuminemia was associated with composite poor outcome (OR 6.97 (95% CI 4.20-11.55), p < 0.001; I2 = 91.3%, p < 0.001). Meta-regression analysis showed that age (p = 0.44), gender (p = 0.76), HT (p = 0.97), DM (p = 0.40), CKD (p = 0.65), liver disease (p = 0.72), and malignancy (p = 0.84) did not affect the association. Subgroup analysis showed that hypoalbuminemia increased mortality (OR 6.26 (95% CI 3.26-12.04), p < 0.001; I2 = 69.6%, p < 0.01) and severity of the disease (OR 7.32 (95%CI 3.94-13.59), p < 0.001; I2 = 92.5%, p < 0.01). Pooled diagnostic analysis of hypoalbuminemia yielded a sensitivity of 0.63 (95% CI 0.52-0.72), specificity of 0.81 (95% CI 0.73-0.87), and AUC of 0.77. The probability of poor outcome was 70% in patients with hypoalbuminemia and 24% in patients with normal albumin level. CONCLUSION: Hypoalbuminemia was associated with poor prognosis in COVID-19 patients.

Validation of the Indonesian Version of the Asian Diabetes Quality of Life Questionnaire.

BACKGROUND: quality of life has been identified as the goal of therapy especially in patient with chronic disease such as type 2 diabetes mellitus. Quality of life measurement requires an instrument that was specifically developed in accordance with socio-cultural background of the measured population. The aim of this study was to adapt Asian Diabetes Quality of Life Questionnaire so it can be used in Indonesia as valid and reliable tool. METHODS: Asian Diabetes Quality of Life Questionnaire was translated and adapted by group of experts, then validity and reliability tests were conducted on type 2 diabetes mellitus patients at Dr. Hasan Sadikin General Hospital, Bandung. Construct validity was analyzed using correlation test between score of each item and total score. Reliability was measured using test-retest method and internal consistency represented in Cronbach's alpha score. RESULTS: validity test showed significant correlation (p-value ≤0.05) between score of each item and total score across all domains with moderate to very strong correlation (r: 0.496-0.956). Reliability test using test-retest method showed no significant difference between Test I and II results (p-value >0.05) with very strong correlation (r: 0.830-0.975) and internal consistency yielded Cronbach's alpha scores of  ≥ 0.07 for all domains. CONCLUSION: Indonesian version of Asian DQOL is a valid and reliable tool to measure quality of life of type 2 diabetes mellitus patients.

In-hospital use of statins is associated with a reduced risk of mortality in coronavirus-2019 (COVID-19): systematic review and meta-analysis.

BACKGROUND AND AIMS: The idea of treating COVID-19 with statins is biologically plausible, although it is still controversial. The systematic review and meta-analysis aimed to address the association between the use of statins and risk of mortality in patients with COVID-19. METHODS: Several electronic databases, including PubMed, SCOPUS, EuropePMC, and the Cochrane Central Register of Controlled Trials, with relevant keywords up to 11 November 2020, were used to perform a systematic literature search. This study included research papers containing samples of adult COVID-19 patients who had data on statin use and recorded mortality as their outcome of interest. Risk estimates of mortality in statin users versus non-statin users were pooled across studies using inverse-variance weighted DerSimonian-Laird random-effect models. RESULTS: Thirteen studies with a total of 52,122 patients were included in the final qualitative and quantitative analysis. Eight studies reported in-hospital use of statins; meanwhile, the remaining studies reported pre-admission use of statins. In-hospital use of statin was associated with a reduced risk of mortality (RR 0.54, 95% CI 0.50-0.58, p < 0.00001; I2: 0%, p = 0.87), while pre-admission use of statin was not associated with mortality (RR 1.18, 95% CI 0.79-1.77, p = 0.415; I2: 68.6%, p = 0.013). The funnel plot for the association between the use of statins and mortality were asymmetrical. CONCLUSION: This meta-analysis showed that in-hospital use of statins was associated with a reduced risk of mortality in patients with COVID-19.

The effect of a structured clinical algorithm on glycemic control in patients with combined tuberculosis and diabetes in Indonesia: A randomized trial.

AIMS: Diabetes mellitus (DM) is associated with worse tuberculosis (TB) treatment outcomes, especially among those with poor glycemic control. We examined whether a structured clinical algorithm could improve glycemic control in TB patients with DM. METHODS: In an open label randomized trial, TB-DM patients were randomized to scheduled counselling, glucose monitoring, and adjustment of medication using a structured clinical algorithm (intervention arm) or routine DM management (control arm), with glycated hemoglobin (HbA1c) at month 6 as the primary end point. RESULTS: We randomized 150 pulmonary TB-DM patients (92% culture positive, 51.3% male, mean age 53 years). Baseline mean HbA1c was 11.0% in the intervention arm (n = 76) and 11.6% in the control arm (n = 74). At 6 months, HbA1c had decreased more in the intervention arm compared with the control arm (a difference of 1.82% HbA1c, 95% CI 0.82-2.83, p < 0.001). Five patients were hospitalized in the intervention arm and seven in the control arm. There was more hypoglycemia (35.0% vs 11.8%; p = 0.002) in the intervention arm. Two deaths occurred in the intervention arm, one due to cardiorespiratory failure and one because of suspected septic shock and multiorgan failure. CONCLUSION: Regular monitoring and algorithmic adjustment of DM treatment led to improved glycemic control.

Effect of increased BMI and obesity on the outcome of COVID-19 adult patients: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Corona virus diseases 2019 (COVID-19) pandemic spread rapidly. Growing evidences that overweight and obesity which extent nearly a third of the world population were associated with severe COVID-19. This study aimed to explore the association and risk of increased BMI and obesity with composite poor outcome in COVID-19 adult patients. METHODS: We conducted a systematic literature search from PubMed and Embase database. We included all original research articles in COVID-19 adult patients and obesity based on classification of Body Mass Index (BMI) and composite poor outcome which consist of ICU admission, ARDS, severe COVID-19, use of mechanical ventilation, hospital admission, and mortality. RESULTS: Sixteen studies were included in meta-analysis with 9 studies presented BMI as continuous outcome and 10 studies presented BMI as dichotomous outcome (cut-off ≥30 kg/m2). COVID-19 patients with composite poor outcome had higher BMI with mean difference 1.12 (95% CI, 0.67-1.57, P < 0.001). Meanwhile, obesity was associated with composite poor outcome with odds ratio (OR) = 1.78 (95% CI, 1.25-2.54, P < 0.001) Multivariate meta-regression showed the association between BMI and obesity on composite poor outcome were affected by age, gender, DM type 2, and hypertension. CONCLUSION: Obesity is a risk factor of composite poor outcome of COVID-19. On the other hand, COVID-19 patients with composite poor outcome have higher BMI. BMI is an important routine procedure that should always be assessed in the management of COVID-19 patients and special attention should be given to patients with obesity.

The Association Between Chronic Kidney Disease and New Onset Renal Replacement Therapy on the Outcome of COVID-19 Patients: A Meta-analysis.

OBJECTIVE: The aim of the study was to evaluate the association between chronic kidney disease (CKD) and new onset renal replacement therapy (RRT) with the outcome of Coronavirus Disease 2019 (COVID-19) in patients. METHODOLOGY: A systematic literature search from several databases was performed on studies that assessed CKD, use of RRT, and the outcome of COVID-19. The composite of poor outcome consisted of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care, and use of mechanical ventilator. RESULTS: Nineteen studies with a total of 7216 patients were included. CKD was associated with increased composite poor outcome (RR 2.63 [1.33, 5.17], P = .03; I 2 = 51%, P = .01) and its subgroup, consisting of mortality (RR 3.47 [1.36, 8.86], P = .009; I 2 = 14%, P = .32) and severe COVID-19 (RR 2.89 [0.98, 8.46], P = .05; I 2 = 57%, P = .04). RRT was associated with increased composite poor outcome (RR 18.04 [4.44, 73.25], P < .001; I 2 = 87%, P < .001), including mortality (RR 26.02 [5.01, 135.13], P < .001; I 2 = 60%, P = .06), severe COVID-19 (RR 12.95 [1.93, 86.82], P = .008; I 2 = 81%, P < .001), intensive care (IC) (RR 14.22 [1.76, 114.62], P < .01; I 2 = 0%, P < .98), and use of mechanical ventilator (RR 34.39 [4.63, 255.51], P < .0005). CONCLUSION: CKD and new-onset RRT were associated with poor outcome in patients with COVID-19.

The use of renin angiotensin system inhibitor on mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

BACKGROUND: and Aims; To investigate the association between use of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB) and outcomes of hypertensive COVID-19 patients, a systematic review and meta-analysis were performed. METHODS: We systematically searched PubMed, EuropePMC, ProQuest, and Cochrane Central Databases using the terms "(COVID-19 OR SARS-CoV-2) AND (angiotensin converting enzyme OR angiotensin receptor blocker)". The primary and second outcomes were mortality (non-survivor) and severe COVID-19, respectively. RESULTS: Totally, 7410 patients were included from 15 studies. Pooled analysis showed that the use of ACEI/ARB was not associated with mortality (OR 0.73 [0.38, 1.40], p = 0.34; I2: 81%) and severity (OR 1.03 [0.73, 1.45], p = 0.87; I2: 65%). Pooled adjusted OR showed no risk/benefit associated with ACEI/ARB use in terms of mortality (OR 0.83 [0.54, 1.27], p = 0.38; I2: 0%). Subgroup analysis showed that the use of ARB was associated with reduced mortality (OR 0.51 [0.29, 0.90], p = 0.02; I2: 22%) but not ACEI subgroup (OR 0.68 [0.39, 1.17], p = 0.16; I2: 0%). Meta-regression showed that the association between ACEI/ARB use and mortality in patients with COVID-19 do not varies by gender (p = 0.104). GRADE showed a very low certainty of evidence for effect of ACEI/ARB on mortality and severity. The certainty of evidence was very low for both ACEI and ARB subgroups. CONCLUSION: Administration of a renin angiotensin system (RAS) inhibitor, was not associated with increased mortality or severity of COVID-19 in patients with hypertension. Specifically, ARB and not ACEI use, was associated with lower mortality.

Is subcutaneous insulin administration adequate for the management of hyperglycemic crisis in COVID-19?

There is a desperate need to explore different insulin administration strategies, particularly in coronavirus disease 2019 (COVID-19) patients with hyperglycemic crisis. Noteworthily, diabetes mellitus (DM) and poorly controlled blood glucose increase the risk of mortality and severity of COVID-19. Intravenous (IV) insulin administration with hourly monitoring of blood glucose is the ideal approach in managing patients with hyperglycemic crisis, but it is not judicious to be applied in developing countries where shortage of personal protective equipment (PPE) is a major issue. Furthermore, increasing the probability of "already greater risks" for doctors or other healthcare workers contracting COVID-19 seems inappropriate. Thus, an alternative administration strategy and more moderate glucose monitoring to reduce the contact exposure of healthcare workers with COVID-19 patients, by ensuring appropriate blood glucose levels, needs to be performed in this critical pandemic era. Subcutaneous (SC) rapid-acting insulin analog administration could presumably be a solution to this contentious issue.

High tuberculosis incidence among people living with diabetes in Indonesia.

BACKGROUND: Data regarding the incidence of tuberculosis (TB) among people living with diabetes (PLWD) in TB-endemic settings are scarce. We examined TB incidence among PLWD in Indonesia who had previously been screened for latent TB infection (LTBI) and TB disease. METHODS: PLWD (≥18 y of age) in an urban setting were examined a mean 3.4 y after they had been screened for active TB and LTBI. Data on subsequent TB diagnosis were collected by interview and with chest X-ray, sputum smear and Mycobacterium tuberculosis culture. TB incidence rates were stratified for baseline LTBI status, as determined by the QuantiFERON interferon-gamma release assay (IGRA). RESULTS: Of 590 PLWD, 101 had died and 163 could not be contacted or refused. Among the 326 who were re-examined, 6 (1.8%; 95% confidence interval [CI] 0.7 to 4.0) reported being diagnosed already and a further 5 were diagnosed with active TB (1.5%; 95% CI 0.50 to 3.5). The TB incidence rate was 9.85 (95% CI 4.03 to 15.68) per 1000 person-years. TB incidence was higher among PLWD with baseline LTBI (17.13; 95% CI 5.25 to 29.00/1000 person-years) compared with those without LTBI (4.79; 95% CI -0.63 to 10.21), with an incidence rate ratio of 3.57 (95% CI 0.86 to 20.92; p=0.054). CONCLUSIONS: PLWD with LTBI in Indonesia and similar settings are likely to benefit from TB preventive therapy.

Rifampicin Alters Metformin Plasma Exposure but Not Blood Glucose Levels in Diabetic Tuberculosis Patients.

The pharmacokinetic (PK) and clinical implications of combining metformin with rifampicin are relevant to increasing numbers of patients with diabetic tuberculosis (TB) across the world and are yet unclear. We assessed the impact of rifampicin on metformin PKs and its glucose-lowering effect in patients with diabetic TB by measuring plasma metformin and blood glucose during and after TB treatment. Rifampicin increased metformin exposure: plasma area under the plasma concentration-time curve from time point 0 to the end of the dosing interval (AUC0-τ ) and peak plasma concentration (Cmax ) geometric mean ratio (GMR; during vs. after TB treatment) were 1.28 (90% confidence interval (CI) 1.13-1.44) and 1.19 (90% CI 1.02-1.38; n = 22). The metformin glucose-lowering efficacy did not change (Δglucose - Cmax ; P = 0.890; n = 18). Thus, we conclude that additional glucose monitoring in this population is not warranted. Finally, 57% of patients on metformin and rifampicin, and 38% of patients on metformin alone experienced gastrointestinal adverse effects. Considering this observation, we advise patients to take metformin and rifampicin with food and preferably separated in time. Clinicians could consider metoclopramide if gastrointestinal adverse effects occur.