Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case-control study.

Background: Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. Methods: The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). Findings: Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50). Interpretation: There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. Funding: The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case­control study

BACKGROUND Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. METHODS The INTERSTROKE study is a case­control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). FINDINGS Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46­1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61­2.11) than ICH (OR 1.19 95% CI 1.00­1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24­4.10) and PAR (18.6%, 15.1­22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63­2.87) and undetermined cause (OR 1.97, 95% CI 1.55­2.50). Both filtered (OR 1.73, 95% CI 1.50­1.99) and non-filtered (OR 2.59, 95% CI 1.79­3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69­2.27), ischemic stroke (OR 1.89, 95% CI 1.59­2.24) and ICH (OR 2.00, 95% CI 1.60­2.50). INTERPRETATION There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. FUNDING The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Mortality and major postoperative complications within 1 year after vascular surgery: a prospective cohort study.

INTRODUCTION: Patients undergoing vascular procedures are prone to developing postoperative complications affecting their short­term mortality. Prospective reports describing the incidence of long­term complications after vascular surgery are lacking. OBJECTIVES: We aimed to describe the incidence of complications 1 year after vascular surgery and to evaluate an association between myocardial injury after noncardiac surgery (MINS) and 1­year mortality. PATIENTS AND METHODS: This is a substudy of a large prospective cohort study Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION). Recruitment took place in 28 centers across 14 countries from August 2007 to November 2013. We enrolled patients aged 45 years or older undergoing vascular surgery, receiving general or regional anesthesia, and hospitalized for at least 1 night postoperatively. Plasma cardiac troponin T concentration was measured before the surgery and on the first, second, and third postoperative day. The patients or their relatives were contacted 1 year after the procedure to assess the incidence of major postoperative complications. RESULTS: We enrolled 2641 patients who underwent vascular surgery, 2534 (95.9%) of whom completed 1­year follow­up. Their mean (SD) age was 68.2 (9.8) years, and the cohort was predominantly male (77.5%). The most frequent 1­year complications were myocardial infarction (224/2534, 8.8%), amputation (187/2534, 7.4%), and congestive heart failure (67/2534, 2.6%). The 1­year mortality rate was 8.8% (223/2534). MINS occurred in 633 patients (24%) and was associated with an increased 1­year mortality (hazard ratio, 2.82; 95% CI, 2.14-3.72; P <0.001). CONCLUSIONS: The incidence of major postoperative complications after vascular surgery is high. The occurrence of MINS is associated with a nearly 3­fold increase in 1­year mortality.

One-year Outcomes after Discharge from Noncardiac Surgery and Association between Predischarge Complications and Death after Discharge: Analysis of the VISION Prospective Cohort Study.

BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.

Accuracy of HemoCue301 portable hemoglobin analyzer for anemia screening in capillary blood from women of reproductive age in a deprived region of Northern Peru: An on-field study.

OBJECTIVE: We aim to assess the accuracy and effectiveness of the HemoCue 301, a point-of-care (POC) device for measuring hemoglobin levels, and detecting anemia among individuals living in Tumbes, a rural, underserved area in Northern Peru. METHODS: Baseline analysis of a clinical trial aimed at assessing the effect of multi-fortified bread (NCT05103709). Adult women with capillary blood HemoCue 301 readings below 12 g/dL were recruited in coastal city of Tumbes, Peru. A total of 306 women took part of the study, venous blood samples were taken and analyzed with an automated hematology analyzer. Serum samples were used to measure ferritin, serum iron and C reactive protein. RESULTS: Capillary blood measured by the Hemocue 301 has a bias of 0.36 ± 0.93 g/dL respect to the automated Hb. More than 50% of women with normal ferritin values were classified as anemics according to the HemoCue 301. Automated Hb cut-off of 10.8 g/dL [AUC 0.82 (0.77-0.88)] had a specificity of 0.817 and a sensitivity 0.711 while with the HemoCue 301 cut-off of 11.1 g/dL [AUC 0.71 (0.62-0.79)] had a specificity of 0.697 and a sensitivity 0.688. The performance of the automated Hb cut-off was significantly better than the HemoCue (p<0.001). CONCLUSION: Caution must be taken when using POC devices, especially with values around the threshold. Cut-off values found in our study could be used as surrogate means when no confirmatory tests are available. Clinical outcomes should be prioritized when diagnosing iron deficiency anemia in women of reproductive age to ensure proper diagnosis.

Association of Psychosocial Stress With Risk of Acute Stroke.

Importance: Psychosocial stress is considered a modifiable risk factor for stroke. Given the prevalence of chronic and acute exposure to stress, it represents a potentially attractive target for population-health interventions. Objectives: To determine the association of psychosocial stress with the risk of acute stroke and explore factors that might modify the association of stress with risk of acute stroke in a large international population. Design, Setting, and Participants: INTERSTROKE is an international retrospective case-control study of risk factors for first acute stroke in 32 countries in Asia, North and South America, Europe, Australia, the Middle East, and Africa. A total of 13 462 patients with stroke and 13 488 matched controls were recruited between January 11, 2007, and August 8, 2015. The present analyses were performed from June 1 to 30, 2021, and included 13 350 cases and 13 462 controls with available data on psychosocial stress. Exposures: Psychosocial stress and occurrence of stressful life events within the preceding year were measured using a standardized questionnaire of self-reported stress at home and work. Main Outcomes and Measures: The association of stress with acute stroke and its subtypes was examined using multivariable conditional logistic regression and factors that might modify the association, particularly self-reported locus of control. Results: Among 26 812 participants included in the analysis, the mean (SD) age of cases was 62.2 (13.6) years; that of controls, 61.3 (13.3) years; 7960 cases (59.6%) and 8017 controls (59.6%) were men. Several periods of stress and permanent stress were reported for 2745 cases (20.5%) and 1933 controls (14.4%), with marked regional variation in prevalence, with the lowest in China (201 of 3981 [5.0%] among controls and 364 of 3980 [9.1%] among cases) and highest in South East Asia (233 of 855 [26.1%] among controls and 241 of 782 [30.8%] among cases). Increased stress at home (odds ratio [OR], 1.95 [95% CI, 1.77-2.15]) and at work (OR, 2.70 [95% CI, 2.25-3.23]) and recent stressful life events (OR, 1.31 [95% CI, 1.19-1.43]) were associated with an increased risk of acute stroke on multivariable analyses (vs no self-reported stress). Higher locus of control at home was associated with a reduced odds of all stroke (OR, 0.73 [95% CI, 0.68-0.79]), and higher locus of control both at work and at home were associated with a lower odds of acute stroke and significantly diminished the association with stress at work (OR, 2.20 [95% CI, 1.88-2.58]; P = .008 for interaction) and home (OR, 1.69 [95% CI, 1.44-1.98]; P < .001 for interaction) for acute stroke. Conclusions and Relevance: Psychosocial stress is a common risk factor for acute stroke. The findings of this case-control study suggest that higher locus of control is associated with lower risk of stroke and may be an important effect modifier of the risk associated with psychosocial stress.

Pilot Feasibility Assessment of a Tailored Physical Activity Prescription in Overweight and Obese People in a Public Hospital.

We aimed to evaluate the feasibility of a tailored physical activity (PA) prescription in overweight and obese people in a tertiary hospital in Lima, Peru. A feasibility pre-post-pilot study was conducted using mixed methods. Participants received a tailored prescription scheme for PA that lasted twelve weeks. It included two prescription sessions, three follow-up phone calls, and three evaluations. Primary feasibility outcomes were recruitment, visits, and phone call adherence. Primary intervention outcomes were self-reported PA levels and the 6 min walk test. Out of 228 people invited to participate, 30 were enrolled and received the first session of prescription, 11 went to the second session, and 21 went to the final evaluation; phone call participation decreased progressively during follow-up. There were no differences in the 6th week and the 12th week compared to the baseline for all the measures, except in the 6 min walk test. The participants considered the intervention was well designed, but they suggested complementing it with dietary instructions. The prescription of PA in overweight and obese people is feasible for promoting PA, but its implementation requires refinements to anticipate possible barriers to changing behavior.

Home-Based Respiratory Physiotherapy and Telephone-Based Psychological Support for COVID-19 Survivors in Peru: Protocol for a Randomized Controlled Trial.

BACKGROUND: Both pulmonary and mental health are affected following hospitalization for COVID-19 pneumonia. Pulmonary rehabilitation therapy has demonstrated benefits in improving mental health, but no validated combined programs that include mental health have been proposed. OBJECTIVE: This article presents the design of a trial that aimed to assess whether the participation in a combined rehabilitation program that includes home-based respiratory physiotherapy and telephone-based psychological support is associated with a greater improvement of pulmonary and mental health outcomes 7-12 weeks after COVID-19 hospitalization discharge compared with posthospital usual care provided by a public Peruvian hospital. METHODS: WAYRA (the word for air in the Quechua language) was an open-label, unblinded, two-arm randomized controlled trial. We recruited 108 participants aged 18-75 years who were discharged from the hospital after COVID-19 pneumonia that required >6 liters/minute of supplemental oxygen during treatment. Participants were randomly assigned at a 1:1 ratio to receive the combined rehabilitation program or usual posthospital care provided by a public Peruvian hospital. The intervention consisted of 12 at-home respiratory rehabilitation sessions and 6 telephone-based psychological sessions. The primary outcome was the 6-minute walk distance. Secondary outcomes included lung function, mental health status (depression, anxiety, and trauma), and quality of life. Outcomes were assessed at baseline (before randomization) and at 7 and 12 weeks after hospital discharge to assess the difference between arms. RESULTS: This study was funded by the Peruvian National Council of Science Technology and Technology Innovation in July 2020. Ethics approval was obtained on September 2, 2020. Recruitment and data collection occurred between October 2020 and June 2021. Results are expected to be published by the end of 2022. CONCLUSIONS: WAYRA was the first randomized controlled trial evaluating combined pulmonary-mental health rehabilitation for hospitalized COVID-19 survivors in resource-limited settings, potentially providing a foundation for the cost-effective scale-up of similar multidisciplinary rehabilitation programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04649736; https://clinicaltrials.gov/ct2/show/NCT04649736. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/36001.

Analysis of medical appointments for patients with overweight and obesity in a public hospital of Lima, Peru: a cross-sectional study of audio-recorded consultations.

OBJECTIVE: To describe the content of overweight and obesity counseling performed in a public Peruvian hospital. METHODS: We audio-recorded 40 visits of patients with overweight or obesity from the internal medicine, cardiology, endocrinology, and family medicine services at Cayetano Heredia Hospital. Fragments of the recordings in which counseling was performed were transcribed and codified. We established a checklist to score each counseling session and performed descriptive analyses. RESULTS: Complete counseling (including weight, nutrition, and physical activity) was performed in 32.5% of consultations. The average time spent in counseling was 1.72 minutes. Counseling on weight loss was performed in 65% of consultations, nutrition in 65%, and physical activity in 35%. On average, 8 of 26 checklist items were fulfilled per appointment. Weight loss goals were established in 15% of visits. The most frequent diet recommendations were eating more fruits and vegetables (32.5%) and eating fewer carbohydrates (30.0%). Suggested physical activities were walking (10.0%), running (7.5%), and playing any sport (7.5%). CONCLUSIONS: Complete counseling was only addressed in one-third of the appointments, and most counseling was superficial without considering therapeutic goals. This suggests the need to include lifestyle counseling in consultations, regardless of the medical specialty or patient's background condition.

Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE).

BACKGROUND AND PURPOSE: The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes. METHODS: Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH). RESULTS: Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P<0.0001). CONCLUSIONS: The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.

Enfermedad de Kawasaki, enfermedad similar a Kawasaki y MIS-C asociado a COVID-19 en niños: revisión sistemática / Kawasaki disease, Kawasaki-like disease, and MIS-C associated with COVID-19 in children: systematic review

Resumen Objetivo: Sintetizar las características epidemiológicas y clínicas de los niños de COVID-19 con EK, KLD y MIS-C. Métodos: Se realizó una búsqueda en 4 bases de datos y preprints hasta el 31 de Mayo del 2021. Se incluyeron reportes/series de caso que evaluaron las caracte rísticas clínicas del EK, KLD o MIS-C en pacientes pediátricos con COVID-19. Resultados: Se incluyeron 16 estudios (seis informes de casos y diez series de casos, 367 pacientes en total, 58 pacientes con EK, 87 con KLD y 290 pacientes con MIS-C); con edades entre los 6 meses y los 10 años, y el 62% eran mujeres. Se observó COVID-19 positivo en 75,2%. Respecto a EK, KLD y MIS-C, las características clínicas repor tadas fueron compatibles con los cuadros diagnósticos estandarizados en el contexto de COVID-19. La duración de la hospitalización fue de 5 a 14 días para EK y de 4,3 a 13 para MIS-C. Once pacientes con MIS-C (2,8%) necesitaron ECMO. Seis pacientes con MIS-C fueron reportados muertos. Ocho estudios reportaron pacientes en la UCI. Conclusiones: EK o KLD puede asociarse a COVID-19 en niños, y pueden complicarse con MIS-C. El tiempo de hospitalización es prolongado si se presenta EK o KLD asociado a COVID-19 en niños.

Abstract Objective: To synthesize the epidemiological and clinical characteristics of COVID-19 children with MIS-C, KLD and EK. Methods: Databases and preprints were searched until May 31, 2021. Reports/case series that evaluated the clinical features of EK, KLD, or MIS-C in pediatric patients with COVID-19 were included. Results: Sixteen studies were included (six case reports and ten case series, 367 patients total, 58 patients with EK, 87 with KLD, and 290 patients with MIS-C); with ages ranging from 6 months to 10 years, and 62% were female. Positive COVID-19 was observed in 75.2%. Regarding EK, KLD and MIS-C, the reported clinical characteristics were compatible with the standardized diagnostic pictures in the context of COVID-19. The duration of hospitalization was 5 to 14 days for EK and 4.3 to 13 for MIS-C. Eleven patients with MIS-C (2.8%) needed ECMO. Eleven patients with MIS-C (2.8%) needed ECMO. Six patients with MIS-C were reported dead. Eight studies reported patients in the ICU. Conclusions: Children with COVID-19 develop EK or KLD, and can be complicated by MIS-C. Prevention, diagnosis, and treatment measures are needed.

Morphine and clinical outcomes in patients with ST segment elevation myocardial infarction treated with fibrinolytic and antiplatelet therapy: Insights from the TREAT trial.

BACKGROUND: Morphine is commonly used to relieve pain, anxiety and dyspnea in STEMI but it lowers blood pressure and delays the activity of oral antiplatelet agents. The impact of morphine on clinical outcomes remains unknown. This analysis was performed to determine if morphine use was associated with increased risk of adverse clinical events among STEMI patients treated with fibrinolytic therapy and clopidogrel or ticagrelor. METHODS: In the Ticagrelor in Patients with ST Elevation Myocardial Infarction Treated with Pharmacological Thrombolysis (TREAT) study, 3799 STEMI patients treated with fibrinolysis were randomized to receive clopidogrel or ticagrelor. Morphine use was left to the discretion of the treating physicians. In this pre-specified analysis, we evaluated clinical outcomes based on the use and timing of morphine administration. Outcomes were stratified by randomized treatment group. Multivariable analysis was performed using Inverse Probability Treatment Weighting (IPTW) weighting. RESULTS: Morphine was used in 53% of patients. After adjustment using IPTW weighting, morphine use was associated with higher hazard of reinfarction at 7 days (HR 4.9, P = .0006) and 30 days (HR 1.7, P = .04), and lower hazard of major bleeding (HR 0.37, P = .006). There was no significant difference in mortality at any time point. CONCLUSIONS: Among patients with STEMI treated with fibrinolytic therapy, morphine use was associated with a higher risk of early reinfarction and a lower risk of major bleeding but no difference in mortality. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02298088.

The road to patient-centred care in Peru: The difficulties and opportunities to achieve participatory health care.

Patient-centred care (PCC) is a pillar of quality health services, where decision-making power is shared between the clinician and the patient. Although, this approach could be adopted with easiness in high income settings or in countries with unified health systems, in settings such as Peru, where universal access and other structural problems remain a challenge, the practice of PCC is not a priority. In Peru, research on PCC has been conducted for almost two decades, but this has not generated a need for development in academia, decision makers, health personnel or patients. Here, we give an overview of the road that PCC research has taken in Peru and the challenges that remain to translate it into clinical practice.

Efectos de una intervención con llamadas telefónicas educativas para mejorar la adherencia y el control metabólico en personas con diabetes mellitus tipo 2 mal controlada: un ensayo clínico aleatorizado / Effects of an Intervention with educational phone calls to improve adherence and metabolic control in people with type 2 diabetes mellitus: a randomized clinical trial

RESUMEN Introducción: Las tecnologías de información y comunicación pueden ayudarnos a mejorar el control metabólico y la adherencia de las personas con diabetes mellitus tipo 2 (DM2). Objetivo: Evaluar los efectos de una intervención con llamadas telefónicas en pacientes ambulatorios con DM2 mal controlada de un hospital en Perú. Métodos: Ensayo clínico aleatorizado. Incluimos adultos con DM2 con mal control glicémico (HbA1c > 7%), quienes fueron aleatorizados al grupo control (cuidado usual) o al grupo intervención (cuidado usual más una intervención con llamadas telefónicas cada dos semanas por tres meses). El desenlace principal fue la reducción ≥ 1% de hemoglobina glicosilada a los tres meses. Resultados: Se reclutó 94 participantes (47 en cada grupo). La edad promedio fue 59,8 años (DE: 10,2), 69,2 % fueron mujeres. A los tres meses, solo 14/47 participantes del grupo control y 13/47 participantes del grupo intervención tuvieron medición de HbA1c. Entre estos, el porcentaje de los que lograron una disminución ≥ 1% de HbA1c fue de 35,7% (5/14) en el grupo control y 53,8% (7/13) en el grupo intervención (RR: 0,72, IC 95%: 0,35-1,47). No se encontró diferencias en la adherencia al tratamiento entre ambos grupos. Conclusiones: No se encontró diferencias estadísticamente significativas para los desenlaces de interés. Posiblemente esto se deba al bajo porcentaje de participantes a los que se logró completar el seguimiento.

ABSTRACT Introduction: Information and communication technologies can help us improve metabolic control and adherence in people with type 2 diabetes mellitus (DM2). Objective: To evaluate the effects of an intervention with telephone calls in outpatients with poorly controlled DM2 in a hospital in Peru. Methods: Randomized clinical trial. We included adults with DM2 with poor glycemic control, who were randomized to the control group (usual care) or to the intervention group (usual care plus a telephone intervention every two weeks for three months). The primary outcome was a ≥ 1% reduction in glycosylated hemoglobin at three months. Results: 94 participants were recruited (47 in each group). Mean age was 59.8 years (SD: 10.2), 69.2 % were women. At three months, only 14/47 participants in the control group and 13/47 participants in the intervention group had HbA1c measurement. Among these, the percentage of those who achieved a ≥ 1% decrease in HbA1c was 35,7% (5/14) in the control group and 53,8% (7/13) in the intervention group (RR: 0,72, 95% CI: 0,35-1,47). No differences were found in adherence to treatment between groups. Conclusions: No statistically significant differences were found for the outcomes of interest. This is possibly due to the low percentage of participants who were able to complete follow-up. Innovative solutions are needed to improve the control of people with DM2.

Efectos de una intervención con llamadas telefónicas educativas para mejorar la adherencia y el control metabólico en personas con diabetes mellitus tipo 2 mal controlada: Un ensayo clínico aleatorizado / Effects of an Intervention with educational phone calls to improve adherence and metabolic control in people with type 2 diabetes mellitus: A randomized clinical trial

Introducción: Las tecnologías de información y comunicación pueden ayudarnos a mejorar el control metabólico y la adherencia de las personas con diabetes mellitus tipo 2 (DM2). Objetivo: Evaluar los efectos de una intervención con llamadas telefónicas en pacientes ambulatorios con DM2 mal controlada de un hospital en Perú. Material y Métodos: Ensayo clínico aleatorizado. Incluimos adultos con DM2 con mal control glicémico (HbA1c > 7%), quienes fueron aleatorizados al grupo control (cuidado usual) o al grupo intervención (cuidado usual más una intervención con llamadas telefónicas cada dos semanas por tres meses). El desenlace principal fue la reducción ≥ 1% de hemoglobina glicosilada a los tres meses. Resultados: Se reclutó 94 participantes (47 en cada grupo). La edad promedio fue 59,8 años (DE: 10,2), 69,2 % fueron mujeres. A los tres meses, solo 14/47 participantes del grupo control y 13/47 participantes del grupo intervención tuvieron medición de HbA1c. Entre estos, el porcentaje de los que lograron una disminución ≥ 1% de HbA1c fue de 35,7% (5/14) en el grupo control y 53,8% (7/13) en el grupo intervención (RR: 0,72, IC 95%: 0,35-1,47). No se encontró diferencias en la adherencia al tratamiento entre ambos grupos. Conclusiones: No se encontró diferencias estadísticamente significativas para los desenlaces de interés. Posiblemente esto se deba al bajo porcentaje de participantes a los que se logró completar el seguimiento.

Introduction: Information and communication technologies can help us improve metabolic control and adherence in people with type 2 diabetes mellitus (DM2). Objective: To evaluate the effects of an intervention with telephone calls in outpatients with poorly controlled DM2 in a hospital in Peru. Material and Methods: Randomized clinical trial. We included adults with DM2 with poor glycemic control, who were randomized to the control group (usual care) or to the intervention group (usual care plus a telephone intervention every two weeks for three months). The primary outcome was a ≥ 1% reduction in glycosylated hemoglobin at three months. Results: 94 participants were recruited (47 in each group). Mean age was 59.8 years (SD: 10.2), 69.2 % were women. At three months, only 14/47 participants in the control group and 13/47 participants in the intervention group had HbA1c measurement. Among these, the percentage of those who achieved a ≥ 1% decrease in HbA1c was 35,7% (5/14) in the control group and 53,8% (7/13) in the intervention group (RR: 0,72, 95% CI: 0,35-1,47). No differences were found in adherence to treatment between groups. Conclusions: No statistically significant differences were found for the outcomes of interest. This is possibly due to the low percentage of participants who were able to complete follow-up. Innovative solutions are needed to improve the control of people with DM2.

Quality of stroke guidelines in low- and middle-income countries: a systematic review.

OBJECTIVE: To identify gaps in national stroke guidelines that could be bridged to enhance the quality of stroke care services in low- and middle-income countries. METHODS: We systematically searched medical databases and websites of medical societies and contacted international organizations. Country-specific guidelines on care and control of stroke in any language published from 2010 to 2020 were eligible for inclusion. We reviewed each included guideline for coverage of four key components of stroke services (surveillance, prevention, acute care and rehabilitation). We also assessed compliance with the eight Institute of Medicine standards for clinical practice guidelines, the ease of implementation of guidelines and plans for dissemination to target audiences. FINDINGS: We reviewed 108 eligible guidelines from 47 countries, including four low-income, 24 middle-income and 19 high-income countries. Globally, fewer of the guidelines covered primary stroke prevention compared with other components of care, with none recommending surveillance. Guidelines on stroke in low- and middle-income countries fell short of the required standards for guideline development; breadth of target audience; coverage of the four components of stroke services; and adaptation to socioeconomic context. Fewer low- and middle-income country guidelines demonstrated transparency than those from high-income countries. Less than a quarter of guidelines encompassed detailed implementation plans and socioeconomic considerations. CONCLUSION: Guidelines on stroke in low- and middle-income countries need to be developed in conjunction with a wider category of health-care providers and stakeholders, with a full spectrum of translatable, context-appropriate interventions.

Workplace Violence Against Physicians Treating COVID-19 Patients in Peru: A Cross-Sectional Study.

BACKGROUND: The COVID-19 pandemic is an unprecedented challenge to health systems that has revealed shortcomings and increased unmet demands. Such situations might exacerbate workplace violence (WPV) against physicians, as has been reported in several parts of the world. METHODS: To identify the frequency and characteristics of WPV suffered by physicians attending COVID-19 patients in Peru, a descriptive, cross-sectional study was conducted with an online survey of 200 physicians. RESULTS: Of the survey respondents, 84.5% had suffered some type of WPV; 97.6% of these suffered nonphysical violence. Suffering more than one incident of violence was reported by 75.7% of respondents. The primary aggressor was a patient's family member or caregiver. Violence occurred most frequently in critical areas inside the health service facility, such as COVID-19 triage, tents, and hospital units, although it also occurred during teleconsultations. Multiple shortcomings of the health services were perceived as the main trigger of violence. Being a female physician (odds ratio [OR] = 2.48, 95% confidence interval [CI] = 1.06-5.83) and working in a COVID-19 ICU (OR = 5.84, 95% CI = 1.60-21.28) were the main factors associated with WPV. CONCLUSION: Violence against physicians attending COVID-19 patients in Peru is common. The perceived factors that contribute most to violence are linked to deficiencies in health services.

[Severe sepsis and retinopathy of prematurity in very low birth weight preterm newborns in a third-level healthcare center in Lima, Peru between 2008 and 2018: A case-control study]. / Sepsis severa y retinopatía de prematuridad en recién nacidos con peso inferior a 1500 gramos al nacer de un hospital de tercer nivel de Lima, Perú en el periodo de 2008 a 2018: estudio de casos y controles.

BACKGROUND: Retinopathy of prematurity is the leading worldwide cause of visual impairment. There is little available data on its epidemiology and related factors and consequences in developing countries such as Peru. Due to this lack of information, we decided to do this study. OBJECTIVES: To evaluate factors related to the development of retinopathy of prematurity in very low birth weight newborn patients. METHODS: We did a case-control (paired 1:1) study of patients admitted to the Neonatal Intensive Care Unit of the Hospital Cayetano Heredia between 2008 and 2018 who had a complete record in the Neocosur network database (N = 293). The case was defined as a preterm newborn patient with a birth weight lower than 1500 grams who developed any type or stage of retinopathy of prematurity; control was defined as a patient with similar characteristics without retinopathy. Univariate and bivariate analysis (using logistic regression model) was performed to obtain the odds ratio with a 95% confidence interval. RESULTS: Data were obtained from 57 cases and 57 controls admitted to the Neonatal Intensive Care Unit at Hospital Cayetano Heredia. Late-onset sepsis was the main factor associated with retinopathy of prematurity (odds ratio 4.39; 95% confidence interval 1.23 to 15.76, p = 0.02). Additionally, we performed a bivariate and multivariate analysis that showed that exposure to supplementary oxygen at 36 weeks of postmenstrual age and retinopathy of prematurity were not significantly associated (8.47; 0.51 to 141.17, p = 0.14). CONCLUSIONS: Patients with late-onset sepsis have a 4.39 times higher odds of developing retinopathy of prematurity. Prospective studies are needed with larger sample sizes.

INTRODUCCIÓN: La retinopatía de la prematuridad es una causa importante de discapacidad visual. Existe poca información sobre la epidemiología, factores asociados con su desarrollo y consecuencias para países de medianos ingresos como Perú. OBJETIVO: Evaluar factores asociados al desarrollo de retinopatía de la prematuridad en recién nacidos pretérmino con peso menor de 1500 gramos. MÉTODOS: Estudio de casos y controles (pareados 1:1) de pacientes admitidos en la unidad de cuidados intensivos neonatales del Hospital Cayetano Heredia durante el periodo de 2008 a 2018, con registro completo en la base de datos de la red Neocosur (N = 293). Caso: paciente recién nacido pretérmino con peso al nacer menor de 1500 gramos, que haya desarrollado cualquier tipo o grado de retinopatía; control: paciente con las mismas características, sin retinopatía. Se realizó análisis bivariado y multivariado (empleando modelo de regresión logística) para obtener Odds ratio, utilizando un intervalo de confianza del 95%. RESULTADOS: La información se obtuvo de 57 casos y 57 controles. El antecedente de sepsis tardía se asocia de manera significativa con el desarrollo de retinopatía de la prematuridad (Odds ratio 4,39; intervalo de confianza 95%; 1,23 a 15,76; p = 0,02). Al realizar el análisis bivariado y el análisis multivariado no se encontró asociación estadísticamente significativa entre la exposición a oxígeno a las 36 semanas de edad postmenstrual y el desarrollo de retinopatía de la prematuridad (Odds ratio 8,47; intervalo de confianza 95%; 0,51 a 141,17; p = 0,14). CONCLUSIONES: En pacientes con antecedente de sepsis tardía, la probabilidad de desarrollar retinopatía de la prematuridad fue 4,39 veces mayor. Se requieren estudios prospectivos que involucren un mayor tamaño muestral.

Renal Impairment and Risk of Acute Stroke: The INTERSTROKE Study.

BACKGROUND: Previous studies reported an association of renal impairment with stroke, but there are uncertainties underpinning this association. AIMS: We explored if the association is explained by shared risk factors or is independent and whether there are regional or stroke subtype variations. METHODS: INTERSTROKE is a case-control study and the largest international study of risk factors for first acute stroke, completed in 27 countries. We included individuals with available serum creatinine values and calculated estimated glomerular filtration rate (eGFR). Renal impairment was defined as eGFR <60 mL/min/1.73 m2. Multivariable conditional logistic regression was used to determine the association of renal function with stroke. RESULTS: Of 21,127 participants, 41.0% were female, the mean age was 62.3 ± 13.4 years, and the mean eGFR was 79.9 ± 23.5 mL/min/1.73 m2. The prevalence of renal impairment was higher in cases (22.9% vs. 17.7%, p < 0.001) and differed by region (p < 0.001). After adjustment, lower eGFR was associated with increased odds of stroke. Renal impairment was associated with increased odds of all stroke (OR 1.35; 95% CI: 1.24-1.47), with higher odds for intracerebral hemorrhage (OR 1.60; 95% CI: 1.35-1.89) than ischemic stroke (OR 1.29; 95% CI: 1.17-1.42) (pinteraction 0.12). The largest magnitudes of association were seen in younger participants and those living in Africa, South Asia, or South America (pinteraction < 0.001 for all stroke). Renal impairment was also associated with poorer clinical outcome (RRR 2.97; 95% CI: 2.50-3.54 for death within 1 month). CONCLUSION: Renal impairment is an important risk factor for stroke, particularly in younger patients, and is associated with more severe stroke and worse outcomes.

Randomized clinical trial to compare the efficacy of ivermectin versus placebo to negativize nasopharyngeal PCR in patients with early COVID-19 in Peru (SAINT-Peru): a structured summary of a study protocol for randomized controlled trial.

OBJECTIVES: The primary objective is to determine the effect of a daily dose of ivermectin administered in three consecutive days to non-severe COVID-19 patients with no more than 96 hours of symptoms, on the detection of SARS-CoV-2 RNA by PCR from nasopharyngeal swabs at day seven post-treatment initiation. The secondary objectives are: 1. To assess the efficacy of ivermectin to reduce the SARS-CoV-2 viral load in the nasopharyngeal swab on days 4, 7, 14 and 21 post-treatment initiation 2. To assess the efficacy of ivermectin on the improvement of symptoms 3. To assess the proportion of seroconversions at day 21 4. To assess the safety of ivermectin at the proposed dose 5. To determine the magnitude of the immune response against SARS-CoV-2 6. To assess correlation of the presence of intestinal helminths on participants on baseline and day 14 with COVID-19 progression and treatment. TRIAL DESIGN: SAINT PERU is a triple-blinded, randomized, placebo-controlled trial with two parallel arms to evaluate the efficacy of ivermectin in negativizing nasopharyngeal PCR in patients with SARS-CoV-2 infection. PARTICIPANTS: The trial is conducted in two national hospitals in Lima-Peru. The study population is patients with a positive PCR test for SARS-CoV-2 in a nasopharyngeal specimen, symptomatic for 96 hours or less, with non-severe COVID-19 disease at baseline, regardless of the presence of risk factors for progression to severity. The study will not include pregnant women or minors (17 years old or younger). Inclusion criteria 1. COVID-19 symptomatology (cough, fever, anosmia, etc.) lasting no more than 96 hours, with a positive nasopharyngeal swab PCR test for SARS-CoV-2. 2. 18 years or older. 3. No use of ivermectin in the month prior to the visit. 4. No known history of ivermectin allergy. 5. Capable to give informed consent. 6. Not current use of CYP 3A4 or P-gp inhibitor drugs such as quinidine, amiodarone, diltiazem, spironolactone, verapamil, clarithromycin, erythromycin, itraconazole, ketoconazole, cyclosporine, tacrolimus, indinavir, ritonavir, cobicistat or critical CYP3A4 substrate drugs such as warfarin. Exclusion criteria 1. COVID-19 pneumonia diagnosed by the attending physician (oxygen saturation < 95% or lung examination) 2. Positive pregnancy test for women at childbearing age. 3. Positive IgG against SARS-CoV-2 by rapid diagnostic test at screening. Participants will be recruited by the investigators at the emergency services of the study sites. They are expected to remain in the trial for a period of 21 days. Follow-up visits will be conducted by the trial medical staff at the participant's home or at a hospital in case of hospitalization. Follow-up visits will assess clinical and laboratory parameters of the patients. INTERVENTION AND COMPARATOR: Ivermectin (300 mcg/kg) or placebo will be administered in one daily dose for three consecutive days. Currently, there is no solid data on the efficacy of ivermectin against the virus in vivo; therefore the use of placebo in the control group is ethically justified. MAIN OUTCOMES: Primary Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment. Secondary 1. Mean viral load as determined by PCR cycle threshold (Ct) on days 4, 7, 14, and 21 2. Proportion of patients with fever and cough at days 4, 7, 14, and 21 as well as proportion of patients progressing to severe disease or death during the trial 2. Proportion of patients with a positive rapid diagnostic test at day 21 3. Proportion of drug-related adverse events during the trial 4. Median levels of IgG, IgM, IgA measured by Luminex RANDOMIZATION: Participants will be randomized to receive one dose of 300 mcg/kg ivermectin or placebo daily for three consecutive days. The epidemiologist will generate a list of correlative numbers, in randomized blocks of size 4, with the assignment to the treatment groups (a and b). The randomization list will be kept in an encrypted file accessible only to the trial statistician. This list will be handed directly to the pharmacist. Independently, the principal investigator will randomly assign the intervention (ivermectin) to one of the two groups (a or b) by tossing a coin, and will inform the pharmacist of the result of this process. The pharmacist will prepare and label the treatment vials according to the randomization list prepared by the epidemiologist and the treatment assignment given by the principal investigator. Eligible patients will be allocated in a 1:1 ratio using this randomization list. BLINDING (MASKING): The clinical trial team, the statistician, and the patients will be blinded as to arm allocation. The vials with placebo will be visibly identical to the ones with the active drug. Treatment will be administered by staff not involved in the clinical care or participant's follow up. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The planned sample size is 186 SARS-CoV-2 PCR positive patients: 93 patients to treatment and 93 to the placebo group. TRIAL STATUS: Current protocol version: 2.0 dated January 15th, 2021. Recruitment started on Aug 29th, 2020. Recruitment is expected to be completed April 30th 2021. TRIAL REGISTRATION: "Ensayo Clínico aleatorizado de Fase IIa para comparar la efectividad de la ivermectina versus placebo en la negativización del PCR en pacientes en fase temprana de COVID-19" Peru National Health Institute REPEC with number: PER-034-20 , registered July 17th 2020 (National Peruvian Registration before the first participant enrolled). "Randomized Phase IIA Clinical Trial to Evaluate the Efficacy of Ivermectin to Obtain Negative PCR Results in Patients With Early Phase COVID-19" Clinicaltrials.gov: NCT04635943 , retrospectively registered in November 19th 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.