The safety of BCG revaccination in the context of COVID-19.

The bacille Calmette-Guérin (BCG) vaccine is administered in many countries as part of their vaccination schedules. Epidemiologic studies have suggested a possible benefit of this vaccine in the context of the COVID-19 pandemic and other respiratory infections. We aimed to assess the safety of this intervention in BCG-primed adults. Adult health care workers (n = 451) received a single intradermal application of the BCG vaccine (Tokyo 172 strain) in the deltoid region of the right arm. Follow-up (30 days) calls and clinical inspections were guided using a standardized data sheet to assess local and systemic reactions. Early local reactions were common at 24 h and 7 days, such as erythema (74.9%, 69.2%), induration (55.7%, 59%), a papule (53.4%, 47.7%), and edema (48.3%, 38.1). Local symptoms (pruritus 44.8%, heat 16.2%, and pain 34.8%) were less frequent at day 7. Late expected reactions (14 and 30 days) included the formation of crusts (39.6% and 63.9%), a pustule (36.6% and 17%), or ulcers (28.8% and 17.7%). Severe reactions were limited to subcutaneous abscesses (2%) and lymphadenitis (<1%).

Retinal Microvascular Density and Perfusion during an Insulin-Induced Hypoglycemia Episode: A Warning Call.

Aim: To evaluate retinal vascular perfusion and density by optical coherence tomography angiography (OCTA) before, during, and after hypoglycemia in individuals with diabetes mellitus with or without diabetic retinopathy (DR). Methods: A focused clinical history was performed, followed by an ophthalmological examination to document retinopathy status. OCTA was performed at baseline, at hypoglycemia, and at glucose normalization. Eye tracking and eye alignment devices on the platform were used to obtain a macular thickness cube (512 × 128) and vascular perfusion and density protocols of 3 × 3 mm. Retinal vascular reactivity was analyzed with superficial plexus vascular perfusion and density protocols on OCTA. Results: Fifty-two participants encompassing 97 eyes fulfilled the eligibility criteria. Their mean age was 42.9 ± 15.1 years (range, 22 to 65), and 20 (38.2%) were men. We found a statistically significant difference in vascular perfusion and density when comparing all groups at baseline. The controls had higher vascular perfusion and density values than the cases. Vascular perfusion and density were significantly reduced in all groups during the hypoglycemia episode, except for vascular density in DR cases. Conclusion: Acute hypoglycemia significantly alters the retinal vascularity in DM patients with and without DR, suggesting that repeated episodes of acute hypoglycemia could exacerbate retinopathy in the long term.

Treatment burden and perceptions of glucose-lowering therapy among people living with diabetes.

AIMS: Address treatment burden and general perceptions of pharmacological treatment in patients with diabetes. METHODS: We surveyed adult patients with diabetes cared for in a tertiary academic medical center about: i) knowledge about the impact of glucose-lowering medication use on diabetes control and complications, ii) common beliefs about natural medicine and insulin use, iii) attitudes towards glucose-lowering medications, iv) burden of treatment, v) general knowledge of diabetes pharmacological treatment, and vi) perceptions of shared decision-making. RESULTS: Two hundred-four participants completed the survey. While most (90%) agreed that adherence to medication would control diabetes and improve quality of life, 30-40% were not certain that it would translate to fewer disease complications. About one of three thought medications could be harmful (29.4%). Over 50% agreed or was unsure that natural remedies were as good/better than prescribed medications. About 30% acknowledged difficulties taking their diabetes medications and monitoring blood glucose, and over 50% were concerned about treatment costs. Nearly 30% denied receiving a detailed explanation from their clinician regarding their disease and is treatment. CONCLUSIONS: Our results highlight the importance of patient education regarding pharmacological treatment for diabetes, and eliciting sources of distress and treatment burden among patients with diabetes.

Autofluorescence indexes as biomarkers for antiangiogenic loading dose outcome in diabetic macular edema.

PURPOSE: To evaluate the combination of fundus autofluorescence results with several clinical and structural variables into mathematical indexes to enhance their ability to predict visual and anatomical changes after the antivascular endothelial growth factor loading dose. METHODS: Patients with diabetic macular edema were enrolled. Each patient had a comprehensive ophthalmological examination, contrast sensitivity, optical coherence tomography, and fundus autofluorescence assessment. All patients received three monthly doses of ziv-aflibercept and were followed each month for response assessment. Autofluorescence was classified according to its level into five grades. The grades were combined with other variables (best-corrected visual acuity, contrast sensitivity, central macular thickness, macular cube volume, and macular cube average thickness) into normalized indexes. Statistical assessment was done using a Spearman's rank correlation coefficient, linear regression, and interobserver-agreement analysis. RESULTS: There was a strong correlation between the fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index at baseline with the best-corrected visual acuity after the third dose of ziv-aflibercept (rs = -0.78, p = .000 and rs = -0.68, p = .0009 respectively). The fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index, both at baseline had a mild correlation with the macular volume at 1 month of follow-up (rs = 0.56, p = .008 and (rs = 0.64, p = .002, respectively). CONCLUSION: This study suggests that it is possible to combine fundus autofluorescence results with functional and structural variables into normalized indexes that could potentially predict outcomes after antivascular endothelial growth factor loading dose in patients with diabetic macular edema.

Participants' awareness of ethical compliance, safety and protection during participation in pharmaceutical industry clinical trials: a controlled survey.

BACKGROUND: The rapid increase of industry-sponsored clinical research towards developing countries has led to potentially complex ethical issues to assess. There is scarce evidence about the perception of these participants about the ethical compliance, security, and protection. We sought to evaluate and contrast the awareness and perception of participants and non-participants of industry-sponsored research trials (ISRT) on ethical, safety, and protection topics. METHODS: A Cases-control survey conducted at twelve research sites in México. Previous and current participants of ISRT (cases) as well as non-participants (controls) with one of four chronic diseases, were asked to complete the survey which focused on ethical compliance and protection issues of ISRT, and the perception of participating in a trial. RESULTS: A total of 604 cases and 604 controls were surveyed. Cases significantly answered that ethics committees are aware of what is happening in studies (50.5% vs. 33.8%, P = ≤ 0.001), and that medical care of industry-sponsored research trials is better than their usual medical care (77.2% vs. 38.2%, P = < 0.001). The same proportion of cases and controls thought patients must receive economical reimbursement for participating in a research study (49.5% vs. 53.1%, P = 0.205). The informed consent of the pharmaceutical clinical trial was fully read by 90.4% of the cases. Most cases were satisfied or very satisfied with their overall study participation (35.6 and 62.3%, respectively). CONCLUSION: Previous and current participants of industry-sponsored research trials have a more positive attitude towards ethics committees, the quality of medical care of the research trials, and the main purpose of economical reimbursements, when compared to non-participants.

Sub-hyaloid and sub-internal limiting membrane macular hemorrhage after laser exposure at music festival: a case report.

PURPOSE: To describe the first case of a combined sub-hyaloid and sub-internal limiting membrane macular hemorrhage after recreational laser exposure. METHODS: A 23-year-old patient presented with an acute loss of vision in his right eye (OD) immediately after a brief exposure to a laser beam at a music festival. Color photography, spectral-domain optical coherence tomography (SD-OCT), and multifocal electroretinogram (mfERG) were performed for diagnosis and follow-up. RESULTS: On presentation, visual acuity was 20/400 in the OD and 20/20 in the left eye. Posterior segment examination of his OD revealed a preretinal hemorrhage at the macula. SD-OCT images exposed a combined sub-hyaloid and sub-internal limiting membrane localization. Successful VPP with ILM peeling was carried out. Although sequential mfERG displayed almost complete restoration of the P1 amplitude 6 months posterior to VPP, SD-OCT demonstrated permanent damage to outer retinal layers. Final BCVA on OD was 20/30. CONCLUSION: The expanding and unregulated use of lasers in everyday life has created an increasing amount of cases of laser-induced retinopathy in recent years. Much more attention should be addressed in laser safety and awareness to prevent future ocular injuries. In acute phases of sub-hyaloid hemorrhages blocking direct visualization of the posterior pole, mfERG is a valuable tool to address initial macular pathology.

Riley-Day Syndrome in a Hispanic Infant of Non-Jewish Ashkenazi Descent.

Riley-Day syndrome is an autosomal recessive sensory and autonomic neuropathy. Patients present a lack of fungiform papilla, alacrima and usually feeding difficulties. It is present almost exclusively in Ashkenazi Jewish individuals and has a poor prognosis. We describe an unusual case of Riley-Day syndrome with pseudostrabismus in a non-Ashkenazi Jewish patient. A one-year-old female infant was referred for evaluation of strabismus, absence of fungiform papillae, feeding difficulty, gastroesophageal reflux and episodes of self-mutilation. Deep tendon reflexes were depressed, the blinking rate and corneal reflex were diminished as well and corneas were opaque due to corneal erosions. Reduced lacrimal production was confirmed by the Schirmer test. Eye drops were recommended every 2-3 hours for corneal erosion and the patient was referred to the genetics department for further diagnostic confirmation.

Participants' perception of pharmaceutical clinical research: a cross-sectional controlled study.

BACKGROUND: There is scarce scientific information assessing participants' perception of pharmaceutical research in developed and developing countries concerning the risks, safety, and purpose of clinical trials. METHODS: To assess the perception that 604 trial participants (cases) and 604 nonparticipants (controls) of pharmaceutical clinical trials have about pharmaceutical clinical research, we surveyed participants with one of four chronic diseases from 12 research sites throughout Mexico. RESULTS: Participation in clinical trials positively influences the perception of pharmaceutical clinical research. More cases (65.4%) than controls (50.7%) perceived that the main purpose of pharmaceutical research is to cure more diseases and to do so more effectively. In addition, more cases considered that there are significant benefits when participating in a research study, such as excellent medical care and extra free services, with this being the most important motivation to participate for both groups (cases 52%, controls 54.5%). We also found a sense of trust in their physicians to deal with adverse events, and the perception that clinical research is a benefit to their health, rather than a risk. More controls believed that clinical trial participants' health is put at risk (57% vs 33.3%). More cases (99.2%) than controls (77.5%) would recommend participating in a clinical trial, and 90% of cases would enroll in a clinical trial again. CONCLUSION: Participation in clinical trials positively influences the perception that participants have about pharmaceutical clinical research when compared to nonparticipants. This information needs to be conveyed to clinicians, public health authorities, and general population to overcome misconceptions.

Glucocorticoid functional reserve in full-spectrum intensity of primary hypothyroidism.

Adrenal function might be impaired in patients with primary hypothyroidism. The objective was to evaluate adrenocortical function using the low-dose cosyntropin test in patients with primary hypothyroidism. Consequently a prospective, longitudinal, controlled study of sixty adult patients with primary hypothyroidism was carried out. Patients naïve to L-T4 treatment were compared with control participants. A low-dose cosyntropin test was done before and after L-T4 therapy. Thirty and sixty minutes after the low-dose cosyntropin, the mean cortisol values were lower in the cases group (612.6 ± 133.1 and 603.4 ± 153.7 nmol/L) when compared to the control group (677.0 ± 82.4 and 669.9 ± 83.7 nmol/L) (P = 0.001 and 0.003), respectively. After L-T4 therapy, this difference was lost. Four out of 60 cases (6.7%) taking a cortisol cutoff value of 500 mmol/L and 11 out of 60 (18.3%) having 550 mmol/L as the cutoff had adrenal insufficiency before L-T4 therapy. After L-T4 therapy, 50% and 81% of the cases had normal cortisol response. In conclusion, patients with different degrees of intensity of primary hypothyroidism had improved cortisol response after reaching euthyroidism. The incidence of adrenal insufficiency was 6.7-18.3% and more than 50% of the cases had a normal cortisol response after L-T4 therapy.

Hemoglobin A1c: a reliable and accurate test for diabetes care? A prospective study in Mexico / Hemoglobina A1c: ¿una prueba precisa y confiable para el cuidado de la diabetes ? Estudio prospectivo en México

Objective. To compare the concordance correlation coefficient for HbA1c results in an in-field experience. Materials and methods. A prospective study in Monterrey, Mexico from April to August 2012 was conducted to evaluate the day-to-day clinical situation when measuring HbA1c. Blood samples from 38 consecutive patients were sent to seven local laboratories and one international reference laboratory. Results. Poor concordance was found in 4 out of 7 laboratories, moderate in 2 out of 7, and significant in just one. HbA1c values from three laboratories fluctuated more than 1% above or below the reference laboratory in more than 30% of cases, and more than 2% in 10%-20% of subjects. Conclusions. Standardized HbA1c measurement has not occurred worldwide. Physicians should be aware of this issue and be cautious of HbA1c guidelines on diabetes diagnosis or management until proper standardization programs are implemented.

Objetivo. Comparar el coeficiente de correlación de concordancia de HbA1c. Material y métodos. Estudio prospectivo en Monterrey, México, de abril a agosto de 2012 para evaluar la medición de la HbA1c. Participaron 38 individuos y se envió la muestra a 7 laboratorios locales y a uno internacional de referencia. Resultados. Se encontró pobre concordancia en 4 de 7 laboratorios, moderada en 2 y una concordancia significativa en uno. Los valores de HbA1c de tres laboratorios fluctuaron más de 1% del laboratorio de referencia en más de 30% de los casos y más de 2% en 10 a 20%. Conclusiones. La estandarización de la HbA1c no está concluida. Los médicos deberían tomar con cautela las recomendaciones de las guías para HbA1c en el diagnóstico o manejo de la diabetes hasta que se implementen los programas de estandarización.

Hyperglycemia related to high-dose glucocorticoid use in noncritically ill patients.

BACKGROUND: Glucocorticoids commonly cause drug-induced diabetes. This association is well recognized but available evidence does not answer clinically relevant issues in subjects without diabetes. METHODS: Thirty-five individuals without diabetes with a recent diagnosis of acute lymphoblastic leukemia or non-Hodgkin's lymphoma on high-dose glucocorticoid therapy were studied. Close systematic monitoring of fasting and postprandial glycemia and fasting insulin determinations, HOMA-insulin resistance and HOMA ß-cell function were performed. The primary objective was to define the incidence of secondary diabetes in patients treated with high-dose glucocorticoids. Secondary objectives were to specify the intensity, the moment it appears and the evolution of hyperglycemia, in addition to the risk factors, mechanisms and impact of continuous and cyclical glucocorticoids on the development of hyperglycemia. RESULTS: Mean age of patients was 38.4 ± 18.7 years. The incidence of diabetes was 40.6% and was found after the first week; half the time it occurred between the second and fourth. Two-thirds spontaneously normalized by eight weeks. Continuous glucocorticoid administration had a higher incidence of fasting hyperglycemia (P = 0.003). Mean peak insulin levels were significantly higher in cases of diabetes. CONCLUSIONS: High-dose prednisone for 2 to 3 months produced an elevated incidence of diabetes, usually with mild hyperglycemia occurring between the second and fourth week, normalizing spontaneously in all cases. Hyperglycemia was more frequent with continuous doses and occurred in cases with increased insulin resistance. The clinical and therapeutic characteristics of our participants, who were otherwise healthy, could represent the clinical setting of many patients with illness from other medical areas that might require high doses of GC for six to twelve weeks.

Hemoglobin A1c: a reliable and accurate test for diabetes care? A prospective study in Mexico.

OBJECTIVE: To compare the concordance correlation coefficient for HbA1c results in an in-field experience. MATERIALS AND METHODS: A prospective study in Monterrey, Mexico from April to August 2012 was conducted to evaluate the day-to-day clinical situation when measuring HbA1c. Blood samples from 38 consecutive patients were sent to seven local laboratories and one international reference laboratory. RESULTS: Poor concordance was found in 4 out of 7 laboratories, moderate in 2 out of 7, and significant in just one. HbA1c values from three laboratories fluctuated more than 1% above or below the reference laboratory in more than 30% of cases, and more than 2% in 10%-20% of subjects. CONCLUSIONS: Standardized HbA1c measurement has not occurred worldwide. Physicians should be aware of this issue and be cautious of HbA1c guidelines on diabetes diagnosis or management until proper standardization programs are implemented.