COVID-19 and pregnancy: A European study on pre- and post-infection medication use

PURPOSE: The COVID-19 pandemic has impacted medication needs and prescribing practices, including those affecting pregnant women. Our goal was to investigate patterns of medication use among pregnant women with COVID-19, focusing on variations by trimester of infection and location. METHODS: We conducted an observational study using six electronic healthcare databases from six European regions (Aragon/Spain; France; Norway; Tuscany, Italy; Valencia/Spain; and Wales/UK). The prevalence of primary care prescribing or dispensing was compared in the 30-day periods before and after a positive COVID-19 test or diagnosis. RESULTS: The study included 294,126 pregnant women, of whom 8943 (3.0%) tested positive for, or were diagnosed with, COVID-19 during their pregnancy. A significantly higher use of antithrombotic medications was observed particularly after COVID-19 infection in the second and third trimesters. The highest increase was observed in the Valencia region where use of antithrombotic medications in the third trimester increased from 3.8% before COVID-19 to 61.9% after the infection. Increases in other countries were lower; for example, in Norway, the prevalence of antithrombotic medication use changed from around 1-2% before to around 6% after COVID-19 in the third trimester. Smaller and less consistent increases were observed in the use of other drug classes, such as antimicrobials and systemic corticosteroids. CONCLUSION: Our findings highlight the substantial impact of COVID-19 on primary care medication use among pregnant women, with a marked increase in the use of antithrombotic medications post-COVID-19. These results underscore the need for further research to understand the broader implications of these patterns on maternal and neonatal/fetal health outcomes

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Efeitos do intervalo de recuperação entre as séries sobre a pressão arterial após exercícios resistidos Efectos del intervalo de recuperación entre las series sobre la presión arterial luego de ejercicios de resistencia Effects of rest interval between exercise sets on blood pressure after resistance exercises

FUNDAMENTO: Apesar de os estudos demonstrarem a ocorrência da hipotensão pós-exercício (HPE) em exercícios resistidos, ainda não há consenso sobre um protocolo ideal. OBJETIVO: Avaliar os efeitos de diferentes intervalos de recuperação (IR) entre séries de exercício resistido (ER) na pressão arterial (PA) pós-exercício. MÉTODOS: Dezesseis homens jovens sedentários e não hipertensos realizaram, de forma contrabalanceada três protocolos de ER com 1 (P1), 2 (P2) e 3 (P3) minutos de IR entre as séries, e um protocolo controle (CON). Os protocolos de ER consistiram em três séries de oito repetições em seis exercícios. As cargas utilizadas na 1ª, 2ª e 3ª série dos exercícios foram respectivamente 80, 70 e 60% de 1 repetição máxima (1RM). As medidas foram realizadas em repouso (REP), 15 (T15), 30 (T30), 45 (T45), 60 (T60), 75 (T75) e 90 (T90) minutos após a sessão. Foi realizada uma análise de variância fatorial (ANOVA) com post hoc LSD. RESULTADOS: Não foi encontrada alteração significativa na PA sistólica após os protocolos. Foi encontrado um aumento significativo da PA diastólica, após o CON, nos momentos T45 e T90. Ocorreu redução significativa na PA diastólica após P1 e P3, com duração de 30 e 15 minutos respectivamente. Não foram encontradas diferenças significativas nas respostas da PA sistólica e diastólica entre os protocolos com diferentes IR. CONCLUSÃO: Parece que o IR não influencia a redução da PA sistólica após uma sessão de ER. No entanto, foi encontrada uma queda na PA diastólica (P1 e P3) com duração de até 30 minutos.<br>FUNDAMENTO: A pesar de que los estudios demuestran la aparición de hipotensión post-ejercicio (HPE) en Ejercicios de Resistencia, aún no existe consenso sobre un protocolo ideal. OBJETIVO: Evaluar los efectos de diferentes intervalos de recuperación (IR) entre series de ejercicios de resistencia (ER) en la presión arterial (PA) post-ejercicio. MÉTODOS: Dieciséis hombres jóvenes sedentarios y no hipertensos realizaron, de forma contrabalanceada, tres protocolos de ER con 1 (P1), 2 (P2) y 3 (P3) min de IR entre las series, y un protocolo control (CON). Los protocolos de ER consistieron en tres series de ocho repeticiones en seis ejercicios. Las cargas utilizadas en la 1ª, 2ª y 3ª serie de los ejercicios fueron respectivamente 80, 70 y 60% de 1RM. Las mediciones fueron realizadas en reposo (REP), 15 (T15), 30 (T30), 45 (T45), 60 (T60), 75 (T75) y 90 (T90) min luego de la sesión. Se realizó un análisis de varianza factorial (ANOVA) con post hoc LSD. RESULTADOS: No se halló alteración significativa en la PA sistólica luego de los protocolos. Se encontró un aumento significativo de la PA diastólica, luego del CON, en los momentos T45 y T90. Ocurrió una reducción significativa en la PA diastólica luego de P1 y P3, con una duración de 30 y 15 min respectivamente. No se hallaron diferencias significativas en las respuestas de la PA sistólica y diastólica entre los protocolos con diferentes IR. CONCLUSIÓN: Parece que el IR no tiene influencia sobre la reducción de la PA sistólica luego de una sesión de ER. Sin embargo, se encontró una caída en la PA diastólica (P1 y P3) con duración de hasta 30 min.<br>BACKGROUND: Although studies have demonstrated the occurrence of postexercise hypotension (PEH) in resistance exercises, there is still no consensus on an ideal protocol. OBJECTIVE: To evaluate the effects of different rest intervals (RI) between resistance exercise (RE) sets on postexercise blood pressure (BP). METHODS: Sixteen sedentary non-hypertensive young men performed three RE protocols with RI of 1 (P1), 2 (2) and 3 (P3) minutes between the sets, as well as a control protocol (CON), in a counterbalanced manner. The RE protocols consisted of three sets of eight repetitions in six exercises. The loads used in the 1st, 2nd, and 3rd exercise sets were 80%, 70% and 60% of one repetition maximum (1RM), respectively. Measurements were taken at rest (RES), 15 (T15), 30 (T30), 45 (T45), 60 (T60), 75 (T75), and 90 (T90) minutes after the session. Factorial analysis of variance (Anova) was carried out, followed by post hoc LSD. RESULTS: No significant change was found in systolic BP after the protocols. A significant increase in diastolic BP was verified after CON at timepoints T45 and T90. Significant reduction in diastolic BP occurred after P1 and P3, with duration of 30 and 15 minutes, respectively. No significant differences were found in the systolic and diastolic BP responses between the protocols with different RI. CONCLUSION: RI does not seem to influence systolic BP reduction after an RE session. However, reductions in diastolic BP (P1 and P3) lasting up to 30 minutes were observed

Chemotherapy for advanced non-small cell lung cancer in the elderly population

ABSTRACT BACKGROUND: Approximately 50% of patients with newly diagnosed non-small cell lung cancer (NSCLC) are over 70 years of age at diagnosis. Despite this fact, these patients are underrepresented in randomized controlled trials (RCTs). As a consequence, the most appropriate regimens for these patients are controversial, and the role of single-agent or combination therapy is unclear. In this setting, a critical systematic review of RCTs in this group of patients is warranted. OBJECTIVES: To assess the effectiveness and safety of different cytotoxic chemotherapy regimens for previously untreated elderly patients with advanced (stage IIIB and IV) NSCLC. To also assess the impact of cytotoxic chemotherapy on quality of life. METHODS: Search methods: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (1966 to 31 October 2014), EMBASE (1974 to 31 October 2014), and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 31 October 2014). In addition, we handsearched the proceedings of major conferences, reference lists from relevant resources, and the ClinicalTrial.gov database. Selection criteria: We included only RCTs that compared non-platinum single-agent therapy versus non-platinum combination therapy, or non-platinum therapy versus platinum combination therapy in patients over 70 years of age with advanced NSCLC. We allowed inclusion of RCTs specifically designed for the elderly population and those designed for elderly subgroup analyses. Data collection and analysis: Two review authors independently assessed search results, and a third review author resolved disagreements. We analyzed the following endpoints: overall survival (OS), one-year survival rate (1yOS), progression-free survival (PFS), objective response rate (ORR), major adverse events, and quality of life (QoL). MAIN RESULTS: We included 51 trials in the review: non-platinum single-agent therapy versus non-platinum combination therapy (seven trials) and non-platinum combination therapy versus platinum combination therapy (44 trials). Non-platinum single-agent versus non-platinum combination therapy Low-quality evidence suggests that these treatments have similar effects on overall survival (hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.72 to 1.17; participants = 1062; five RCTs), 1yOS (risk ratio (RR) 0.88, 95% CI 0.73 to 1.07; participants = 992; four RCTs), and PFS (HR 0.94, 95% CI 0.83 to 1.07; participants = 942; four RCTs). Non-platinum combination therapy may better improve ORR compared with non-platinum single-agent therapy (RR 1.79, 95% CI 1.41 to 2.26; participants = 1014; five RCTs; low-quality evidence). Differences in effects on major adverse events between treatment groups were as follows: anemia: RR 1.10, 95% 0.53 to 2.31; participants = 983; four RCTs; very low-quality evidence; neutropenia: RR 1.26, 95% CI 0.96 to 1.65; participants = 983; four RCTs; low-quality evidence; and thrombocytopenia: RR 1.45, 95% CI 0.73 to 2.89; participants = 914; three RCTs; very low-quality evidence. Only two RCTs assessed quality of life; however, we were unable to perform a meta-analysis because of the paucity of available data. Non-platinum therapy versus platinum combination therapy Platinum combination therapy probably improves OS (HR 0.76, 95% CI 0.69 to 0.85; participants = 1705; 13 RCTs; moderate-quality evidence), 1yOS (RR 0.89, 95% CI 0.82 to 0.96; participants = 813; 13 RCTs; moderate-quality evidence), and ORR (RR 1.57, 95% CI 1.32 to 1.85; participants = 1432; 11 RCTs; moderate-quality evidence) compared with non-platinum therapies. Platinum combination therapy may also improve PFS, although our confidence in this finding is limited because the quality of evidence was low (HR 0.76, 95% CI 0.61 to 0.93; participants = 1273; nine RCTs). Effects on major adverse events between treatment groups were as follows: anemia: RR 2.53, 95% CI 1.70 to 3.76; participants = 1437; 11 RCTs; low-quality evidence; thrombocytopenia: RR 3.59, 95% CI 2.22 to 5.82; participants = 1260; nine RCTs; low-quality evidence; fatigue: RR 1.56, 95% CI 1.02 to 2.38; participants = 1150; seven RCTs; emesis: RR 3.64, 95% CI 1.82 to 7.29; participants = 1193; eight RCTs; and peripheral neuropathy: RR 7.02, 95% CI 2.42 to 20.41; participants = 776; five RCTs; low-quality evidence. Only five RCTs assessed QoL; however, we were unable to perform a meta-analysis because of the paucity of available data. AUTHORS' CONCLUSIONS: In people over the age of 70 with advanced NSCLC who do not have significant co-morbidities, increased survival with platinum combination therapy needs to be balanced against higher risk of major adverse events when compared with non-platinum therapy. For people who are not suitable candidates for platinum treatment, we have found low-quality evidence suggesting that non-platinum combination and single-agent therapy regimens have similar effects on survival. We are uncertain as to the comparability of their adverse event profiles. Additional evidence on quality of life gathered from additional studies is needed to help inform decision makin

Efectos del intervalo de recuperación entre las series sobre la presión arterial luego de ejercicios de resistencia

FUNDAMENTO: Apesar de os estudos demonstrarem a ocorrência da hipotensão pós-exercício (HPE) em exercícios resistidos, ainda não há consenso sobre um protocolo ideal. OBJETIVO: Avaliar os efeitos de diferentes intervalos de recuperação (IR) entre séries de exercício resistido (ER) na pressão arterial (PA) pós-exercício. MÉTODOS: Dezesseis homens jovens sedentários e não hipertensos realizaram, de forma contrabalanceada três protocolos de ER com 1 (P1), 2 (P2) e 3 (P3) minutos de IR entre as séries, e um protocolo controle (CON). Os protocolos de ER consistiram em três séries de oito repetições em seis exercícios. As cargas utilizadas na 1ª, 2ª e 3ª série dos exercícios foram respectivamente 80, 70 e 60% de 1 repetição máxima (1RM). As medidas foram realizadas em repouso (REP), 15 (T15), 30 (T30), 45 (T45), 60 (T60), 75 (T75) e 90 (T90) minutos após a sessão. Foi realizada uma análise de variância fatorial (ANOVA) com post hoc LSD. RESULTADOS: Não foi encontrada alteração significativa na PA sistólica após os protocolos. Foi encontrado um aumento significativo da PA diastólica, após o CON, nos momentos T45 e T90. Ocorreu redução significativa na PA diastólica após P1 e P3, com duração de 30 e 15 minutos respectivamente. Não foram encontradas diferenças significativas nas respostas da PA sistólica e diastólica entre os protocolos com diferentes IR. CONCLUSÃO: Parece que o IR não influencia a redução da PA sistólica após uma sessão de ER. No entanto, foi encontrada uma queda na PA diastólica (P1 e P3) com duração de até 30 minutos.BACKGROUND: Although studies have demonstrated the occurrence of postexercise hypotension (PEH) in resistance exercises, there is still no consensus on an ideal protocol. OBJECTIVE: To evaluate the effects of different rest intervals (RI) between resistance exercise (RE) sets on postexercise blood pressure (BP). METHODS: Sixteen sedentary non-hypertensive young men performed three RE protocols with RI of 1 (P1), 2 (2) and 3 (P3) minutes between the sets, as well as a control protocol (CON), in a counterbalanced manner. The RE protocols consisted of three sets of eight repetitions in six exercises. The loads used in the 1st, 2nd, and 3rd exercise sets were 80%, 70% and 60% of one repetition maximum (1RM), respectively. Measurements were taken at rest (RES), 15 (T15), 30 (T30), 45 (T45), 60 (T60), 75 (T75), and 90 (T90) minutes after the session. Factorial analysis of variance (Anova) was carried out, followed by post hoc LSD. RESULTS: No significant change was found in systolic BP after the protocols. A significant increase in diastolic BP was verified after CON at timepoints T45 and T90. Significant reduction in diastolic BP occurred after P1 and P3, with duration of 30 and 15 minutes, respectively. No significant differences were found in the systolic and diastolic BP responses between the protocols with different RI. CONCLUSION: RI does not seem to influence systolic BP reduction after an RE session. However, reductions in diastolic BP (P1 and P3) lasting up to 30 minutes were observed.FUNDAMENTO: A pesar de que los estudios demuestran la aparición de hipotensión post-ejercicio (HPE) en Ejercicios de Resistencia, aún no existe consenso sobre un protocolo ideal. OBJETIVO: Evaluar los efectos de diferentes intervalos de recuperación (IR) entre series de ejercicios de resistencia (ER) en la presión arterial (PA) post-ejercicio. MÉTODOS: Dieciséis hombres jóvenes sedentarios y no hipertensos realizaron, de forma contrabalanceada, tres protocolos de ER con 1 (P1), 2 (P2) y 3 (P3) min de IR entre las series, y un protocolo control (CON). Los protocolos de ER consistieron en tres series de ocho repeticiones en seis ejercicios. Las cargas utilizadas en la 1ª, 2ª y 3ª serie de los ejercicios fueron respectivamente 80, 70 y 60% de 1RM. Las mediciones fueron realizadas en reposo (REP), 15 (T15), 30 (T30), 45 (T45), 60 (T60), 75 (T75) y 90 (T90) min luego de la sesión. Se realizó un análisis de varianza factorial (ANOVA) con post hoc LSD. RESULTADOS: No se halló alteración significativa en la PA sistólica luego de los protocolos. Se encontró un aumento significativo de la PA diastólica, luego del CON, en los momentos T45 y T90. Ocurrió una reducción significativa en la PA diastólica luego de P1 y P3, con una duración de 30 y 15 min respectivamente. No se hallaron diferencias significativas en las respuestas de la PA sistólica y diastólica entre los protocolos con diferentes IR. CONCLUSIÓN: Parece que el IR no tiene influencia sobre la reducción de la PA sistólica luego de una sesión de ER. Sin embargo, se encontró una caída en la PA diastólica (P1 y P3) con duración de hasta 30 min