Rodríguez‐Gutiérrez, René

Background: Combined therapy with levothyroxine (LT4)/L-triiodothyronine (LT3) has garnered attention among clinicians and patients as a potential treatment alternative to LT4 monotherapy. The objective of this study was to compare the benefits and harms of LT4/LT3 combined therapy and LT4 monotherapy for patients with hypothyroidism. Methods: A systematic search in MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials was performed by a librarian from inception date until September 2020. Randomized clinical trials and quasiexperimental studies comparing combined therapy (LT4/LT3) versus monotherapy (LT4) for adult patients with hypothyroidism were considered for inclusion. Independent data extraction was performed by paired reviewers. A meta-analysis comparing standardized mean differences of the effect of each therapy was performed on clinical outcomes and patient preferences. Proportions of adverse events and reactions were assessed narratively. Results: A total of 1398 references were retrieved, from which 18 fulfilled the inclusion criteria. Results supported by evidence at low-to-moderate certainty evidence did not display a difference in treatment effect between therapies on clinical status, quality of life, psychological distress, depressive symptoms, and fatigue; all measured with standardized questionnaires. Furthermore, meta-analysis of patient preferences revealed higher proportions of choice for combined therapy (43%) when compared with monotherapy (23%) or having no preference (30%). When evaluating treatment adverse events or adverse reactions, similar proportions were observed between treatment groups; meta-analysis was not possible. Conclusions: The available evidence at low-to-moderate certainty demonstrates that there is no difference in clinical outcomes between LT4/LT3 combined therapy and LT4 monotherapy for treating hypothyroidism in adults, except for a higher proportion of patient preferring combined therapy. Adverse events and reactions appear to be similar across both groups, however, this observation is only narrative. These results could inform shared decision-making conversations between patients with hypothyroidism and their clinicians. PROSPERO Registration ID: CRD42020202658.

Introduction Observational studies constitute an important evidence base for hypoglycemia in diabetes management. This requires consistent and reliable ascertainment and reporting methodology, particularly in studies of type 2 diabetes where hypoglycemia risk is heterogeneous. Therefore, we aimed to examine the definitions of hypoglycemia used by observational studies of patients with type 2 diabetes. Research design and methods We conducted a meta-epidemiological review of observational studies reporting on hypoglycemia or evaluating glucose-lowering medications in adults with type 2 diabetes. MEDLINE and Google Scholar were searched from January 1970 to May 2018. The definitions of non-severe, severe and nocturnal hypoglycemia were examined. Results We reviewed 243 studies: 47.7% reported on non-severe hypoglycemia, 77.8% on severe hypoglycemia and 16.9% on nocturnal hypoglycemia; 5.8% did not specify. Among 116 studies reporting non-severe hypoglycemia, 18.1% provided no definition, 23.3% used glucose values, 38.8% relied on patient-reported symptoms, 17.2% accepted either glucose values or patient-reported symptoms and 2.6% relied on International Classification of Disease (ICD) codes. Among 189 studies reporting severe hypoglycemia, 11.1% provided no definition, 53.4% required symptoms needing assistance, 3.7% relied on glucose values, 14.8% relied on ICD codes, 2.6% relied on ICD codes or glucose values and 15.9% required both symptoms needing assistance and glucose values. Overall, 38.2% of non-severe and 67.7% of severe hypoglycemia definitions were consistent with the International Hypoglycemia Study Group. Conclusions The marked heterogeneity in how hypoglycemia is defined in observational studies may contribute to the inadequate understanding and correction of hypoglycemia risk factors among patients with type 2 diabetes.

AbstractAimThe aim of this study was to systematically appraise the quality of a sample of COVID-19-related systematic reviews (SRs) and discuss internal validity threats affecting the COVID-19 body of evidence.DesignWe conducted a scoping review of the literature. SRs with or without meta-analysis (MA) that evaluated clinical data, outcomes or treatments for patients with COVID-19 were included.Main outcome measuresWe extracted quality characteristics guided by A Measurement Tool to Assess Systematic Reviews-2 to calculate a qualitative score. Complementary evaluation of the most prominent published limitations affecting the COVID-19 body of evidence was performed.ResultsA total of 63 SRs were included. The majority were judged as a critically low methodological quality. Most of the studies were not guided by a pre-established protocol (39, 62%). More than half (39, 62%) failed to address risk of bias when interpreting their results. A comprehensive literature search strategy was reported in most SRs (54, 86%). Appropriate use of statistical methods was evident in nearly all SRs with MAs (39, 95%). Only 16 (33%) studies recognised heterogeneity in the definition of severe COVID-19 as a limitation of the study, and 15 (24%) recognised repeated patient populations as a limitation.ConclusionThe methodological and reporting quality of current COVID-19 SR is far from optimal. In addition, most of the current SRs fail to address relevant threats to their internal validity, including repeated patients and heterogeneity in the definition of severe COVID-19. Adherence to proper study design and peer-review practices must remain to mitigate current limitations.

Background: The use of prescribed medications during pregnancy is a challenge and an underestimated source of treatment burden. Levothyroxine (LT4) for the treatment of overt and subclinical hypothyroidism is extensively prescribed during pregnancy. To this end, we aimed to explore the patients' perceived benefits and risks, knowledge, beliefs, attitudes, and related burden of LT4 therapy during pregnancy. Methods: In this cross-sectional study, we surveyed pregnant women who were treated with LT4 during pregnancy from January 1, 2019, to December 31, 2019, in a tertiary academic medical center of the United States. The anonymous online survey included questions to gather demographic data and multiple-choice questions regarding the benefits and risks, knowledge, beliefs, attitudes, and burden related to LT4 use during pregnancy. Results: Sixty-four pregnant women (mean age 31.5 years) completed the study survey (response rate: 96%): 62% were diagnosed with hypothyroidism more than 12 months before pregnancy, 16% less than or about 12 months before pregnancy, and 22% during pregnancy. We found that one-third of pregnant women using LT4 had a feeling of uneasiness/anxiety due to their hypothyroidism diagnosis. About half of the respondents (45%) reported that they did not receive an explanation by their clinician regarding the maternal/fetal risks of uncontrolled hypothyroidism or the benefits of adequate control. Finally, two in three patients expressed various concerns of LT4-related treatment burden. Conclusions: Our findings support the need for increased effective communication and tailored counseling to address fears, anxiety, and uncertainties about the benefits and risks of LT4 use in pregnancy. For patients with clear benefits from LT4 treatment in pregnancy, it could help to overcome their concerns, promote adherence, and decrease adverse maternal/fetal outcomes. For patients with no clear benefits established, clinicians need to be aware of LT4-related treatment burden in pregnancy and implement patient-centered approaches in their clinical practices.

Abstract Coronavirus disease 2019 (Covid-19) has affected millions of people and may disproportionately affect those with hypertension and diabetes. Because of inadequate methods in published systematic reviews, the prevalence of diabetes and hypertension and associated risks of poor outcomes in Covid-19 patients are unknown. We searched databases from December 1, 2019, to April 6, 2020, and selected observational peer-reviewed studies in English of patients with Covid-19. Independent reviewers extracted data on study participants, interventions, and outcomes and assessed risk of bias, and the certainty of evidence. We included 65 (15 794 participants) observational studies at moderate to high risk of bias. Overall prevalence of diabetes and hypertension was 12% (95% confidence interval [CI], 10-15; n = 12 870; I2: 89%), and 17% (95% CI, 13-22; n = 12 709; I2: 95%), respectively. In severe Covid-19, the prevalence of diabetes and hypertension were 18% (95% CI, 16-20; n = 1099; I2: 0%) and 32% (95% CI, 16-54; n = 1078; I2: 63%), respectively. Unadjusted relative risk for intensive care unit admission and mortality were 1.96 (95% CI, 1.19-3.22; n = 8890; I2: 80%; P = .008) and 2.78 (95% CI, 1.39-5.58; n = 2058; I2: 75%; P = .0004) for diabetics; and 2.95 (95% CI, 2.18-3.99; n = 1737; I2: 0%; P < .001) and 2.39 (95% CI, 1.54-3.73; n = 3107; I2: 66%; P < .001) for hypertensives. Neither diabetes (1.50; 95% CI, 0.90-2.50; n = 1991; I2: 74%; P = .119) nor hypertension (1.48; 95% CI, 0.99-2.23; n = 2023; I2: 69%; P = .058) was associated with severe Covid-19. In conclusion, the risk of intensive care unit admission and mortality for patients with diabetes or hypertension who developed Covid-19 is increased compared with those without these comorbidities. PROSPERO registration number CRD42020176582.

AbstractObjectiveTo assess the risk of gestational diabetes mellitus (GDM) according to the triglyceride and glucose (TyG) index values during the first trimester of pregnancy in Latin American women.MethodsPregnant women were enrolled at their first prenatal visit at the Obstetric Division in the University Hospital “Dr. José E. González”. Triglycerides and fasting plasma glucose (FPG) were collected to determine the TyG index. GDM diagnosis was performed by a single‐step 2‐hour 75‐g oral glucose tolerance test. Generalized linear models were used to determine risk ratios; pregnancy outcomes at delivery were collected from the hospital medical records.ResultsA total of 164 pregnant women were included. GDM was present in 29 (17.7%) women. No significant differences in age, first‐trimester body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), family history of diabetes, and TyG index were observed between GDM cases and the reference group without GDM. The adjusted analysis showed no association between TyG and GDM (risk ratio [RR] 1.03, 95% confidence interval [CI] 0.57–1.88]). Higher TyG index values between women with and without a diagnosis of GDM in the second trimester were observed. No significant differences were identified in pregnancy outcomes, although a trend was observed for hyperbilirubinemia in women with first‐trimester TyG index values greater than 8.7.ConclusionsOur findings do not support the use of the TyG index for GDM prediction in Latin American women.

Introduction . The triglyceride and glucose (TyG) index has been described as a biochemical marker of insulin resistance (IR); however, its diagnostic accuracy remains uncertain. Objective . To summarize the evidence assessing the diagnostic accuracy of the TyG index regarding IR. Methods . A comprehensive search in MEDLINE, EMBASE, Web of Science, and Scopus was performed without any language restriction. Studies assessing the diagnostic accuracy of the TyG index against the hyperinsulinemic-euglycemic clamp (HIEC) or any other IR biochemical were assessed independently and in duplicate. Diagnostic accuracy measures (sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios) were extracted independently and in duplicate. The QUADAS-2 tool was used to assess the risk of bias of independent studies. Results . We identified 15 eligible studies with 69,922 participants and an overall quality of low to moderate. The TyG index was evaluated by HIEC and HOMA as reference tests. The highest achieved sensitivity was 96% using HIEC, and the highest specificity was of 99% using HOMA-IR, with a cutoff value of 4.68. AUC values varied from 0.59 to 0.88. Cutoff values for IR were variable between studies, limiting its comparability. Conclusion . In this systematic review, we found moderate-to-low quality evidence about the usefulness of the TyG index as a surrogate biochemical marker of IR. Due to the lack of a standardized IR definition and heterogeneity between studies, further validation and standardized cutoff values are needed to be used in clinical practice.