Implementation and Evaluation of a mHealth-Based Community Health Worker Feedback Loop for Hispanics with and at Risk for Diabetes.

BACKGROUND: Gaps in accessibility and communication hinder diabetes care in poor communities. Combining mobile health (mHealth) and community health workers (CHWs) into models to bridge these gaps has great potential but needs evaluation. OBJECTIVE: To evaluate a mHealth-based, Participant-CHW-Clinician feedback loop in a real-world setting. DESIGN: Quasi-experimental feasibility study with intervention and usual care (UC) groups. PARTICIPANTS: A total of 134 participants (n = 67/group) who were all low-income, uninsured Hispanics with or at-risk for type 2 diabetes. INTERVENTION: A 15-month study with a weekly to semimonthly mHealth Participant-CHW-Clinician feedback loop to identify participant issues and provide participants monthly diabetes education via YouTube. MAIN MEASURES: We used pre-defined feasibility measures to evaluate our intervention: (a) implementation, the execution of feedback loops to identify and resolve participant issues, and (b) efficacy, intended effects of the program on clinical outcomes (baseline to 15-month HbA1c, systolic blood pressure (SBP), diastolic blood pressure (DBP), and weight changes) for each group and their subgroups (at-risk; with diabetes, including uncontrolled (HbA1c ≥ 7%)). KEY RESULTS: CHWs identified 433 participant issues (mean = 6.5 ± 5.3) and resolved 91.9% of these. Most issues were related to supplies, 26.3% (n = 114); physical health, 23.1% (n = 100); and medication access, 20.8% (n = 90). Intervention participants significantly improved HbA1c (- 0.51%, p = 0.03); UC did not (- 0.10%, p = 0.76). UC DBP worsened (1.91 mmHg, p < 0.01). Subgroup analyses revealed HbA1c improvements for uncontrolled diabetes (intervention: - 1.59%, p < 0.01; controlled: - 0.72, p = 0.03). Several variables for UC at-risk participants worsened: HbA1c (0.25%, p < 0.01), SBP (4.05 mmHg, p < 0.01), DBP (3.21 mmHg, p = 0.01). There were no other significant changes for either group. CONCLUSIONS: A novel mHealth-based, Participant-CHW-Clinician feedback loop was associated with improved HbA1c levels and identification and resolution of participant issues. UC individuals had several areas of clinical deterioration, particularly those at-risk for diabetes, which is concerning for progression to diabetes and disease-related complications. CLINICAL TRIAL: NCT03394456, accessed at https://clinicaltrials.gov/ct2/show/NCT03394456.

The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection.

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant NEIL2 in A549-ACE2 cells shows decreased expression of proinflammatory genes and viral E-gene, as well as lowers the yield of viral progeny compared to mock-treated cells. Mechanistically, NEIL2 cooperatively binds to the 5'-UTR of SARS-CoV-2 genomic RNA to block viral protein synthesis. Collectively, these data strongly suggest that the maintenance of basal NEIL2 levels is critical for the protective response of hosts to viral infection and disease.

Determining call-to-entry rate and recruitment barriers in clinical studies for community clinics serving low-income populations: a cohort study.

BACKGROUND: Recruitment for clinical studies is challenging. To overcome barriers, investigators have previously established call-to-entry rates to assist in planning. However, rates specific to low-income minority populations are needed to account for additional barriers to enrolment these individuals face. OBJECTIVE: To obtain a call-to-entry rate in a low-income uninsured Hispanic population with chronic disease. METHODS: We used data from four of our randomised clinical studies to determine the call-to-entry rate for individuals (n=1075) with or at risk for type 2 diabetes: participants needed/potential participants contacted=recruitment rate (yield). Research staff contacted potential participants to enrol in a study that evaluated 6 month diabetes programmes at community clinics from 2015 to 2020. We recorded call-to-entry rates, reasons for declining the study, show rates, and attrition. RESULTS: The call-to-entry rate was 14.5%. Forty per cent of potential participants could not be contacted, and 30.6%, 19.1%, and 5.4% responded yes, no, and maybe, respectively. No show percentages were 54% for yes and 91.4% for maybe responders. The majority (61.6%) declined due to inability to attend; reasons to decline included work (43%), eligibility (18%), transportation (10%), out of town (9%), did not think they needed the programme (7%) and other/unknown (14%). Being a physician predicted inability to reach participants (adjusted OR 2.91, 95% CI 1.73 to 4.90). Attrition was 6.8%. CONCLUSIONS: We described a call-to-entry rate and detailed recruitment data, including reasons to decline the study. This valuable information can assist investigators in study planning and overcoming enrolment barriers in low-income populations. Telehealth-based or strategies that limit transportation needs may increase participant involvement. TRIAL REGISTRATION NUMBER: NCT03394456.

Tocilizumab Is Associated with Increased Risk of Fungal Infections among Critically Ill Patients with COVID-19 and Acute Renal Failure: An Observational Cohort Study.

RESEARCH QUESTION: Does treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19? BACKGROUND: Numerous therapies have been evaluated as possible treatments for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor that has found a role as a therapy for patients with severe coronavirus-19 pneumonia. The immunomodulatory effects of tocilizumab may have the unintended consequence of predisposing recipients to secondary infections. We sought to assess the risk of invasive fungal disease and the therapeutic impact of tocilizumab on the hospital length of stay, duration of mechanical ventilation, and intensive-care-unit length of stay in critically ill patients with severe coronavirus-19 pneumonia. METHODS: Records of critically ill patients with coronavirus-2019 admitted from March to September 2020 at our institution were reviewed. The risk for fungal infections, intensive-care-unit length of stay, hospital length of stay, and duration of mechanical ventilation in those that received tocilizumab in addition to standard coronavirus-2019 treatments was assessed. RESULTS: Fifty-six critically ill patients treated with dexamethasone and remdesivir for coronavirus-2019 were included, of which 16 patients also received tocilizumab. The majority of the cohort was African American, Asian, or of other ethnic minorities (53.6%). Invasive fungal infections occurred in 10.7% of all patients, and infection rates were significantly higher in the tocilizumab group than in the control group (31.2% vs. 2.5%, risk difference [RD] = 28.8%, p < 0.01). The increased risk in the tocilizumab group was strongly associated with renal replacement therapy. There was a dose-response relationship between the risk of fungal infection and number of tocilizumab doses received, with 2.5% of infections occurring with zero doses, 20% with a single dose (RD = 17.5%), and 50% with two doses (RD = 47.5%) (trend test p < 0.001). In addition, ICU LOS (23.4 days vs. 9.0 days, p < 0.01), the duration of mechanical ventilation (18.9 vs. 3.5 days, p = 0.01), and hospital length of stay (LOS) (29.1 vs. 15.5, p < 0.01) were increased in patients that received tocilizumab. CONCLUSIONS: Repurposed immunomodulator therapies, such as tocilizumab, are now recommended treatments for severe coronavirus-2019 pneumonia, but safety concerns remain. In this early pandemic cohort, the addition of tocilizumab to dexamethasone was associated with an increased risk of fungal infection in those that were critically ill and received renal replacement therapy. Tocilizumab use was also associated with increased ICU and hospital LOSs and duration of mechanical ventilation.

Premedication with midazolam in low-risk surgery in children does not reduce postoperative delirium. Prospective cohort study

Introduction: Pediatric postoperative delirium is a frequent complication for which preventive pharmacological measures have been suggested. The use of midazolam as a prophylactic strategy has not yet been thoroughly assessed. Notwithstanding the fact that it is used in pediatric presurgical separation anxiety, its role in delirium is yet to be established. Objective: To quantify the incidence of pediatric postoperative delirium in patients undergoing low risk surgical interventions, exposed to oral midazolam-based premedication and to explore the protective and risk factors associated with the development of delirium. Methods: Prospective, analytical observational study with a cohort design. Children were conveniently selected in accordance with the daily list of surgical procedures in the operating rooms. The inclusion criteria were children between 2 and 10 years old, ASA I-II, undergoing low risk surgeries. Concurrent and longitudinal follow-up was then conducted upon admission to the post-anesthesia care unit (PACU) for the first hour. Results: A total of 518 children were included. The overall incidence of delirium was 14.4 % (95 % CI: 11.4 %-17.5 %). In the subgroup exposed to midazolam, 178 children were analyzed, with an incidence of delirium of 16.2% (95% CI of 10,8 %-21,7). These patients exhibited a higher tendency to delirium with the use of sevoflurane or fentanyl, and/orwhen presenting with severe postoperative pain. Patients exposed to propofol and/or remifentanil showed lower incidences. Conclusions: No reduction in the incidence of emergency pediatric delirium associated with the use of pre-surgical oral midazolam in low risk surgical procedures. Prospective controlled trials and additional research are required to study the effectiveness and safety of this intervention.

Introducción: El delirio pediátrico posoperatorio es una complicación frecuente para la cual se han sugerido medidas farmacológicas de prevención. El uso de midazolam como estrategia profiláctica aún no ha sido suficientemente evaluado. A pesar de que se emplea para la ansiedad de separación pediátrica prequirúrgica, su papel en delirio aún no se ha establecido. Objetivo: Cuantificar la incidencia de delirio pediátrico posoperatorio en pacientes sometidos a cirugías de bajo riesgo quirúrgico, expuestos a premedicación basada en midazolam oral y adicionalmente, explorar los factores protectores y de riesgo asociados a la ocurrencia. Materiales y métodos: Estudio observacional analítico prospectivo con un diseño de cohorte. Se seleccionaron niños por conveniencia de acuerdo con la lista quirúrgica diaria en salas de cirugía. Como criterios de inclusión se tomaron sujetos entre 2 y 10 años de edad, ASA 1-11, sometidos a cirugías de bajo riesgo quirúrgico. Posteriormente se realizó seguimiento concurrente y longitudinal al ingreso a la unidad de recuperación posanestésica (UCPA) durante la primera hora de estancia. Resultados: Se incluyeron 518 niños. La incidencia global de delirio fue del 14,4 % (IC 95 %;11,4 %-17,5 %). En el subgrupo expuesto a midazolam se analizaron 178 niños, quienes presentaron una incidencia de delirio del 16,2 % (IC 95 %;10,8 %-21,7 %). Estos pacientes presentaron una mayor tendencia a delirio con el uso de sevofluorano o fentanilo, y/o cuando presentaron dolor severo posoperatorio. Pacientes con exposición a propofol y/o remifentanilo exhibieron incidencias inferiores. Conclusiones: No se encontró una reducción en la incidencia de delirio pediátrico de emergencia asociada al empleo de midazolam oral prequirúrgico en cirugías de bajo riesgo. Se requieren estudios prospectivos controlados e investigación adicional para el estudio de la efectividad y seguridad de esta intervención.

Factors associated with posoperative mortality in high perioperative risk patients. Cohort study / Factores asociados a mortalidad posoperatoria en pacientes de alto riesgo perioperatorio. Estudio de cohorte

Abstract Introduction: Determining perioperative risk is part of the strategies implemented with the aim of reducing morbidity and mortality in the surgical population in the world. Although there is no established definition, high perioperative risk is associated with the group of patients with the highest disease burden. Objective: To determine postoperative mortality and its associated factors in patients with high perioperative risk. Methods: Analytical observational cohort study of high perioperative risk patients included in the database (n = 843) of the anesthesia program in a high complexity hospital in Colombia, between January 2011 and April 2018. Pre and postoperative variables were analyzed using uni and multivariate logistic regression per protocol. Overall and stratified mortality were estimated and factors associated with their occurrence were analyzed. Finally, survival was analyzed, the primary outcome being overall cohort mortality and stratified high cardiovascular risk mortality. Results: Cumulative 7-day mortality was 3.68% (95% CI 2.40-4.95%) and 30-day mortality was 10.08% (95% CI 8.05-12.12%). Perioperative mortality in the high cardiovascular risk group in the first 7 days was 3.60% (95% CI 1.13-6.07%) and 14.86% (95% CI 10.15-19.58%) at 30 days. The following preoperative variables were associated with mortality: chronic obstructive pulmonary disease, chronic kidney disease, limited functional class and abdominal aortic aneurysm. A strong association was observed between postoperative complications and a significant increase in mortality rate; the most relevant complications were cerebrovascular events and cardiogenic shock. Conclusions: In this group of high perioperative risk patients, and in the subgroup of high cardiovascular risk patients, overall mortality at 7 and at 30 days was estimated to be above values reported in various countries. Mortality was significantly increased by the presence of preoperative factors and postoperative complications.

Resumen Introducción: La determinación del riesgo perioperatorio hace parte de las estrategias de reducción de la morbimortalidad en la población quirúrgica mundial. El alto riesgo perioperatorio, a pesar de no tener una definición establecida, corresponde al grupo con mayor carga de enfermedad. Objetivo: Establecer la mortalidad posoperatoria en pacientes de alto riesgo perioperatorio y sus factores asociados. Métodos: Estudio observacional analítico con diseño de cohorte, que incluyó pacientes del programa de anestesiología de alto riesgo perioperatorio de un hospital de alta complejidad en Colombia. Base de datos compuesta por n = 843, entre enero de 2011 y abril de 2018. Se analizaron variables pre y posoperatorias mediante regresión logística uni y multivariada por protocolo. Se calculó la mortalidad global y estratificada y se analizaron factores asociados a su ocurrencia. Finalmente, se realizó análisis de supervivencia. El desenlace primario fue la mortalidad global de la cohorte y la mortalidad estratificada para el alto riesgo cardiovascular. Resultados: La mortalidad acumulada a los primeros 7 días fue de 3,68 % (IC 95 %; 2,40 %-4,95 %) y a los 30 días 10,08 % (IC 95 %; 8,05 %-12,12 %). La mortalidad perioperatoria en el grupo de alto riesgo cardiovascular a los primeros 7 días fue de 3,60 % (IC 95 %; 1,13 %-6,07 %) y a los 30 días 14,86 % (IC 95 %; 10,15 %-19,58 %). Las siguientes variables preoperatorias estuvieron asociadas a la mortalidad: enfermedad pulmonar obstructiva crónica, enfermedad renal crónica, clase funcional limitada y aneurisma de aorta abdominal. Se observó una fuerte asociación entre complicaciones posoperatorias y un significativo incremento de la tasa de mortalidad; los más relevantes fueron el evento cerebro-vascular y el choque cardiogénico. Conclusiones: En este grupo de pacientes de alto riesgo perioperatorio, la mortalidad global a los 7 días y a los 30 días, y en el subgrupo de alto riesgo cardiovascular, se estimó por encima de los valores reportados en diversos países. La presencia de factores preoperatorios y las complicaciones posoperatorias aumentaron significativamente la mortalidad.

The DNA glycosylase NEIL2 plays a vital role in combating SARS-CoV-2 infection.

Compromised DNA repair capacity of individuals could play a critical role in the severity of SARS-CoV-2 infection-induced COVID-19. We therefore analyzed the expression of DNA repair genes in publicly available transcriptomic datasets of COVID-19 patients and found that the level of NEIL2, an oxidized base specific mammalian DNA glycosylase, is particularly low in the lungs of COVID-19 patients displaying severe symptoms. Downregulation of pulmonary NEIL2 in CoV-2-permissive animals and postmortem COVID-19 patients validated these results. To investigate the potential roles of NEIL2 in CoV-2 pathogenesis, we infected Neil2-null (Neil2-/-) mice with a mouse-adapted CoV-2 strain and found that Neil2-/- mice suffered more severe viral infection concomitant with increased expression of proinflammatory genes, which resulted in an enhanced mortality rate of 80%, up from 20% for the age matched Neil2+/+ cohorts. We also found that infected animals accumulated a significant amount of damage in their lung DNA. Surprisingly, recombinant NEIL2 delivered into permissive A549-ACE2 cells significantly decreased viral replication. Toward better understanding the mechanistic basis of how NEIL2 plays such a protective role against CoV-2 infection, we determined that NEIL2 specifically binds to the 5'-UTR of SARS-CoV-2 genomic RNA and blocks protein synthesis. Together, our data suggest that NEIL2 plays a previously unidentified role in regulating CoV-2-induced pathogenesis, via inhibiting viral replication and preventing exacerbated proinflammatory responses, and also via its well-established role of repairing host genome damage.

Chronic pain-related consultations to the emergency department of children with complex pain conditions: A retrospective analysis of healthcare utilization and costs.

Background: There is limited information regarding the effects of pediatric chronic pain management on the number and cost of chronic pain-related emergency department (ED) consultations. Aim: This retrospective study aimed to evaluate the number and costs of chronic pain-related ED consultations of children and adolescents with chronic pain conditions at the Montreal Children's Hospital (MCH). Methods: Charts of patients followed by the Edwards Family Interdisciplinary Center for Complex Pain (CCP) of the MCH between April 2017 and December 2018 were reviewed. ED consultations, specialist consultations, medication prescriptions, hospital admissions, and outpatient consultation referrals were assessed for the period of 1 year before and after the patients' first consultation with the CCP. Associated costs were also calculated. Results: One-hundred sixty-eight patients were included in the analysis. Fifty-one percent consulted the ED and had 151 chronic pain-related ED consultations within 1 year before their initial CCP consultation. In the year following their first CCP consultation, 52 patients (31%) consulted the ED, of which 24 consultations were chronic pain-related (84% reduction). There was an 81% reduction in the costs associated with chronic pain-related ED consultations within 1 year after CCP management. In addition, there was a significant reduction in ED interventions within 1 year after CCP management, though there was no change in medication prescriptions, hospital admissions, or subspecialist consultations. Conclusion: Children and adolescents with chronic pain conditions had fewer chronic pain-related ED consultations within 1 year after the first evaluation by an interdisciplinary center for complex pain, contributing to reduced ED costs.

Contexte : L'information sur les effets de la prise en charge de la douleur chronique pédiatrique sur le nombre et le coût des consultations liées à la douleur chronique au service des urgences est limitée.Objectif : Cette étude rétrospective visait à évaluer le nombre et le coût des consultations liées à la douleur chronique des enfants et des adolescents souffrant de douleur chronique au service des urgences de l'Hôpital de Montréal pour enfants.Méthodes : Les dossiers de patients suivis par le Centre interdisciplinaire de la famille Edwards pour la douleur complexe (CCP) de l'Hôpital de Montréal pour enfants entre avril 2017 et décembre 2018 ont été examinés. Les consultations au service des urgences, les consultations de spécialistes, les ordonnances de médicaments, les admissions à l'hôpital et les références pour consultation externe ont été évaluées pour la période d'un an avant et après la première consultation des patients auprés du CCP. Les coûts associés ont également été calculés.Résultats : Cent soixante-huit patients ont été inclus dans l'analyse. Cinquante et un pour cent ont consulté le service des urgences dans le cadre de 151 consultations liées à la douleur chronique au service des urgences au cours de l'année précédant leur première consultation au CCP. Dans l'année suivant leur première consultation au CCP, 52 patients (31 %) ont consulté le service des urgences. Vingt-quatre de ces consultations étaient liées à la douleur chronique (une réduction de 84 %). Une réduction de 81 % des coûts associés aux consultations liées à la douleur chronique au service des urgences a été observée dans l'année suivant la prise en charge par le CCP. En outre, une réduction significative des interventions du services des urgences dans l'année suivant la prise en charge par le CCP a été observée, bien quéil néy ait pas eu de changement dans les ordonnances de médicaments, les admissions à léhôpital ou les consultations de sous-spécialistes.Conclusion : Les enfants et les adolescents souffrant de douleur chronique ont consulté le service des urgences pour la douleur chronique moins souvent dans l'année suivant la première évaluation par un centre interdisciplinaire pour la douleur complexe, contribuant ainsi à réduire les coûts du service des urgences.

Temporal Variations in Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Infections by Race and Ethnicity in Arkansas.

Background: The aim of this study was to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates in the small rural state of Arkansas, using SARS-CoV-2 antibody prevalence as an indicator of infection. Methods: We collected residual serum samples from adult outpatients seen at hospitals or clinics in Arkansas for non-coronavirus disease 2019 (COVID-19)-related reasons. A total of 5804 samples were identified over 3 time periods: 15 August-5 September 2020 (time period 1), 12 September-24 October 2020 (time period 2), and 7 November-19 December 2020 (time period 3). Results: The age-, sex-, race-, and ethnicity-standardized SARS-CoV-2 seroprevalence during each period, from 2.6% in time period 1 to 4.1% in time period 2 and 7.4% in time period 3. No statistically significant difference in seroprevalence was found based on age, sex, or residence (urban vs rural). However, we found higher seroprevalence rates in each time period for Hispanics (17.6%, 20.6%, and 23.4%, respectively) and non-Hispanic Blacks (4.8%, 5.4%, and 8.9%, respectively) relative to non-Hispanic Whites (1.1%, 2.6%, and 5.5%, respectively). Conclusions: Our data imply that the number of Arkansas residents infected with SARS-CoV-2 rose steadily from 2.6% in August to 7.4% in December 2020. There was no statistical difference in seroprevalence between rural and urban locales. Hispanics and Blacks had higher rates of SARS-CoV-2 antibodies than Whites, indicating that SARS-CoV-2 spread disproportionately in racial and ethnic minorities during the first year of the COVID-19 pandemic.

State-wide random seroprevalence survey of SARS-CoV-2 past infection in a southern US State, 2020.

The purpose of this cross-sectional study was to estimate the proportion of Arkansas residents who were infected with the SARS-CoV-2 virus between May and December 2020 and to assess the determinants of infection. To estimate seroprevalence, a state-wide population-based random-digit dial sample of non-institutionalized adults in Arkansas was surveyed. Exposures were age, sex, race/ethnicity, education, occupation, contact with infected persons, comorbidities, height, and weight. The outcome was past COVID-19 infection measured by serum antibody test. We found a prevalence of 15.1% (95% CI: 11.1%, 20.2%) by December 2020. Seropositivity was significantly elevated among participants who were non-Hispanic Black, Hispanic (prevalence ratio [PRs]:1.4 [95% CI: 0.8, 2.4] and 2.3 [95% CI: 1.3, 4.0], respectively), worked in high-demand essential services (PR: 2.5 [95% CI: 1.5, 4.1]), did not have a college degree (PR: 1.6 [95% CI: 1.0, 2.4]), had an infected household or extra-household contact (PRs: 4.7 [95% CI: 2.1, 10.1] and 2.6 [95% CI: 1.2, 5.7], respectively), and were contacted in November or December (PR: 3.6 [95% CI: 1.9, 6.9]). Our results indicate that by December 2020, one out six persons in Arkansas had a past SARS-CoV-2 infection.

Bacillus of Calmette and Guérin (BCG) and the risk of leprosy in Ciudad del Este, Paraguay, 2016-2017.

OBJECTIVES: Paraguay has experienced a 35% reduction in the detected incidence of leprosy during the last ten years, as the vaccination coverage against tuberculosis (Bacillus of Calmette and Guérin [BCG] vaccine) reached ≥95% among infants. The objective of this case-control study was to evaluate the protective effect of BCG on the risk of leprosy. METHODS: We used a population-based case-control study of 20 leprosy confirmed cases reported among residents of Ciudad del Este, Paraguay, diagnosed in 2016-2017. Three controls were selected from a random sample of households from the city. We assessed vaccine effectiveness using 1- odds ratio [OR], and confounding for age, gender, education, occupation, and marital status using stratified and exact logistic regression, and explored if there was effect modification calculating the synergy factor (SF) and relative excess risk due to interaction (RERI). RESULTS: After controlling for age, gender, education, occupation and marital status, the OR of BCG scar on the risk of leprosy was 0.10 (95% confidence interval [CI], 0.02 to 0.45), for an estimate of vaccine effectiveness of 89.5% reduced risk of leprosy (95% CI, 55.2 to 98.1). There was evidence of heterogeneity by which the effectiveness of BCG seemed stronger among younger persons (Breslow-Day and Z-test of the SF had a p<0.05), and both the RERI and SF indicated a less then multiplicative and additive interaction of BCG and younger age. CONCLUSIONS: BCG vaccination was associated with a decreased risk of leprosy in the study population, particularly in persons born after 1980.

Transnasal Sphenopalatine Ganglion Block for the Preventive Treatment of Chronic Daily Headache in Adolescents.

Chronic headaches are a major source of morbidity in the pediatric population, affecting physical function, school attendance, social capacity, mood, and sleep. In adults, repetitive sphenopalatine ganglion (SPG) blockade has been studied as a preventive treatment for chronic migraines. This case series aims to evaluate the SPG block for the preventive treatment of chronic daily headache (CDH) in adolescents. We prospectively evaluated 17 adolescents (14 females, 14 ± 1 year) with CDH not responding to cognitive behavioral therapy (CBT), physiotherapy, and standard medications. Each patient received 10 SPG blocks (two blocks/week) using the Tx360® device. At the end of treatment, 10 patients (59%) reported a Patient's Global Impression of Change (PGIC) score ≥ 67%, and 3 months after the end of treatment, nine patients (53%) sustained a PGIC ≥ 67%. There was also a statistically significant reduction in the depression subscale of the Revised Children's Anxiety and Depression Scale (RCADS) at the end of treatment and 3 months post-treatment compared with baseline. The procedure was well tolerated with no adverse effects. In our study, the use of repeat SPG blockade was associated with sustained benefits on the PGIC and the depression subscale of the RCADS when used as preventive headache treatment in adolescents with refractory CDH.

Mast cell stabilizer ketotifen fumarate reverses inflammatory but not neuropathic-induced mechanical pain in mice.

INTRODUCTION: Mast cell (MC) activation could establish a positive feedback loop that perpetuates inflammation and maintains pain. Stabilizing MCs with ketotifen fumarate (KF) may disrupt this loop and relieve pain. OBJECTIVE: We aimed to test the effect of treatment with KF in pain assays in mice and in a case series of patients with chronic widespread pain. METHODS: The analgesic effect of KF was tested in CD-1 mice injected with formalin, complete Freund's adjuvant, or subjected to spared nerve injury. In addition, wild-type (C57BL/6) and MC-deficient (C57BL/6-Kit W-sh/W-sh) mice were injected with formalin or complete Freund's adjuvant and treated with KF. Patients with chronic widespread pain (n = 5; age: 13-16 years) who failed to respond to standard of care participated in a 16-week treatment trial with KF (6 mg/d). Ketotifen fumarate's therapeutic effect was evaluated using the patient global impression of change. RESULTS: In the mouse experiments, KF produced dose- and MC-dependent analgesic effects against mechanical allodynia in the acute and chronic inflammatory pain but not neuropathic pain assays. In the patient case series, 4 patients reported that activity limitations, symptoms, emotions, and overall quality of life related to their pain condition were "better" or "a great deal better" since beginning treatment with KF. This was accompanied by improvements in pain comorbid symptoms. CONCLUSION: Treatment with KF is capable of reducing established inflammatory-induced mechanical nociception in an MC-dependent manner in mice, and it may be beneficial for the treatment of chronic pain conditions.

Intrapulmonary administration of purified NEIL2 abrogates NF-κB-mediated inflammation.

Aberrant or constitutive activation of nuclear factor kappa B (NF-κB) contributes to various human inflammatory diseases and malignancies via the upregulation of genes involved in cell proliferation, survival, angiogenesis, inflammation, and metastasis. Thus, inhibition of NF-κB signaling has potential for therapeutic applications in cancer and inflammatory diseases. We reported previously that Nei-like DNA glycosylase 2 (NEIL2), a mammalian DNA glycosylase, is involved in the preferential repair of oxidized DNA bases from the transcriptionally active sequences via the transcription-coupled base excision repair pathway. We have further shown that Neil2-null mice are highly sensitive to tumor necrosis factor α (TNFα)- and lipopolysaccharide-induced inflammation. Both TNFα and lipopolysaccharide are potent activators of NF-κB. However, the underlying mechanism of NEIL2's role in the NF-κB-mediated inflammation remains elusive. Here, we have documented a noncanonical function of NEIL2 and demonstrated that the expression of genes, such as Cxcl1, Cxcl2, Cxcl10, Il6, and Tnfα, involved in inflammation and immune cell migration was significantly higher in both mock- and TNFα-treated Neil2-null mice compared with that in the WT mice. NEIL2 blocks NF-κB's binding to target gene promoters by directly interacting with the Rel homology region of RelA and represses proinflammatory gene expression as determined by co-immunoprecipitation, chromatin immunoprecipitation, and electrophoretic mobility-shift assays. Remarkably, intrapulmonary administration of purified NEIL2 via a noninvasive nasal route significantly abrogated binding of NF-κB to cognate DNA, leading to decreased expression of proinflammatory genes and neutrophil recruitment in Neil2-null as well as WT mouse lungs. Our findings thus highlight the potential of NEIL2 as a biologic for inflammation-associated human diseases.

Use of bisphosphonates in a retrospective case series of children and adolescents with complex regional pain syndrome.

BACKGROUND: There is increasing evidence for the use of bisphosphonates to treat Complex Regional Pain Syndrome in adults. However, there are scarce data for their use in children with Complex Regional Pain Syndrome. AIM: This retrospective case series aimed to analyze the effects of intravenous bisphosphonate use in children and adolescents with Complex Regional Pain Syndrome enrolled in a multidimensional pain treatment program. METHODS: We analyzed the data of 16 patients (15 females and 1 male, mean age 14 ± 3 years) who received infusions of zoledronic acid (0.015 ± 0.0044mg/kg), pamidronate (0.72 ± 0.17mg/kg), or both depending on their initial response between October 2014 and December 2019. The primary endpoint of the study was the patient's global impression of change. Secondary outcomes included pain intensity, physical function, role function (school attendance), need for pain medications, and adverse effects. RESULTS: Nine of 16 patients reported meaningful improvements (global impressions of change of 84% or higher) at a median follow-up time of 16 (8-21) months after their last infusion of bisphosphonates. There were also meaningful reductions in pain intensity and the need for pain medications. There was an increase in the proportion of patients with minimal or without physical disability, and almost all patients normalized their school activities. Thirteen patients (81%) reported adverse effects, mostly flu-like symptoms, for a few days after the infusion. CONCLUSION: The use of bisphosphonate infusions may represent an effective treatment option for children with Complex Regional Pain Syndrome, not responding to multidisciplinary pain treatment programs.

Osteoporosis severa: fundamentos para su terapia farmacológica en México / Severe osteoporosis: Principles for pharmacological therapy in Mexico

Antecedentes: El presente artículo muestra la evidencia y recomendaciones de la eficacia y seguridad de las terapias hasta hoy aprobadas y disponibles en México para el tratamiento de la osteoporosis en su etapa severa o establecida, con la finalidad de establecer una postura terapéutica acerca de la eficacia y seguridad para esta etapa del padecimiento, de acuerdo con las cédulas descriptivas del Cuadro Básico y Catálogo de Medicamentos del Sector Salud en México. Métodos: Se realizó una revisión sistemática y narrativa de la evidencia de teriparatida y denosumab, desde su perfil farmacológico, efectividad y seguridad derivado de ensayos clínicos, además de un análisis de las recomendaciones generales de las principales guías de práctica clínica nacionales e internacionales. Resultados: La evidencia establece que teriparatida y denosumab pertenecen a clases terapéuticas distintas, con mecanismos de acción biológicamente opuestos e indicaciones de uso claramente diferenciadas en sus respectivas cédulas, por lo cual no son sustituibles ni intercambiables en la terapia de osteoporosis severa. Ambas representan la mejor opción disponible hasta el momento para esta etapa del padecimiento. Son similares en su eficacia de prevención de nuevas fracturas vertebrales por fragilidad, con un RR de 0,35 (IC 95%: 0,22-0,55) para teriparatida, y de 0,32 (IC 95%: 0,26-0,41) para denosumab. La reducción absoluta del riesgo es mayor con teriparatida 9,3% (21 meses) que con denosumab 4,8% (36 meses). Conclusiones: Nuestros resultados concuerdan con las recomendaciones disponibles en las principales guías de práctica clínica nacionales e internacionales, por lo que son propuestas ambas terapias como consecutivas y nunca como sustitutivas.(AU)

Background: This article presents evidence and recommendations regarding the efficacy and safety of the approved and available therapies in Mexico to treat severe or established osteoporosis with the aim of developing a position regarding therapeutics in this stage of the disease, according to the descriptive cards of the National Drug Formulary of the National General Health Council of Mexico. Methods: We performed a systematic and narrative review of the evidence of teriparatide and denosumab, from their pharmacological profile, effectiveness, and safety derived from clinical trials, as well as an analysis of the general recommendations of the national and international clinical practice guidelines. Results: The evidence establishes that teriparatide and denosumab belong to different therapeutic classes, with biologically opposed mechanisms of action and indications of use, which are clearly differentiated in their respective national codes, therefore these drugs cannot be substitutable or interchangeable in severe osteoporosis therapy. Both represent the best options currently available for this stage of the disease; being similar in their efficacy in preventing new vertebral fragility fractures, with an RR of .35 (CI 95%; .22-.55) for teriparatide, and .32 (CI 95%: .26-.41) for denosumab. The absolute risk reduction is higher with teriparatide 9.3% (21 months) compared with denosumab at 4.8% (36 months). Conclusions: Our results agree with the recommendations available in national and international clinical practice guidelines, with both therapies proposed as a sequential, but not a substitute, treatment.(AU)

Severe osteoporosis: Principles for pharmacological therapy in Mexico. / Osteoporosis severa: fundamentos para su terapia farmacológica en México.

BACKGROUND: This article presents evidence and recommendations regarding the efficacy and safety of the approved and available therapies in Mexico to treat severe or established osteoporosis with the aim of developing a position regarding therapeutics in this stage of the disease, according to the descriptive cards of the National Drug Formulary of the National General Health Council of Mexico. METHODS: We performed a systematic and narrative review of the evidence of teriparatide and denosumab, from their pharmacological profile, effectiveness, and safety derived from clinical trials, as well as an analysis of the general recommendations of the national and international clinical practice guidelines. RESULTS: The evidence establishes that teriparatide and denosumab belong to different therapeutic classes, with biologically opposed mechanisms of action and indications of use, which are clearly differentiated in their respective national codes, therefore these drugs cannot be substitutable or interchangeable in severe osteoporosis therapy. Both represent the best options currently available for this stage of the disease; being similar in their efficacy in preventing new vertebral fragility fractures, with an RR of .35 (CI 95%; .22-.55) for teriparatide, and .32 (CI 95%: .26-.41) for denosumab. The absolute risk reduction is higher with teriparatide 9.3% (21 months) compared with denosumab at 4.8% (36 months). CONCLUSIONS: Our results agree with the recommendations available in national and international clinical practice guidelines, with both therapies proposed as a sequential, but not a substitute, treatment.

Utilizing Telemedicine for Group Visit Provider Encounters: A Feasibility and Acceptability Study.

BACKGROUND: The value of telemedicine has been underscored during the coronavirus pandemic. Utilizing telemedicine could markedly enhance group visit scalability and sustainability. However, there are limited data demonstrating telemedicine use for group visits. OBJECTIVE: To evaluate the feasibility and acceptability of provider encounters conducted via telemedicine in group visits. MATERIALS AND METHODS: We conducted a 6-month diabetes group visit program and compared in-person (months 1-3) versus telemedicine (videoconferencing) (months 4-6) patient-provider encounters. Participants completed the Telehealth Usability Questionnaire (TUQ) at 6-months (primary outcome). To ensure telemedicine did not negatively affect clinical outcomes, we compared in-person versus telemedicine differences in HbA1c, blood pressure, body mass index (BMI), and attendance. RESULTS: The TUQ revealed that participants (N=19) found telemedicine useful and easy to use (4.9/5.0, 4.4/5.0, respectively) and with excellent interface (4.3/5.0), interaction (4.6/5.0), reliability (4.2/5.0), and satisfaction (4.4/5.0). There were no significant differences in clinical outcomes between arms: HbA1c (in-person: -0.60%, telemedicine: -0.52%, p=0.86), blood pressure (systolic: p=0.475, diastolic: p=0.683), weight (p=0.982), BMI (p=0.981), attendance (in-person: 75.44%, telemedicine: 70.12%, p=0.551). CONCLUSION: Provider telemedicine encounters in group visits are feasible and acceptable. This is a promising model to address provider limitations in group visits and increase access to care. Larger studies are needed to further evaluate these findings.