Thalidomide in the treatment of erythema nodosum leprosum (ENL): systematic review of clinical trials and prospects of new investigations

FUNDAMENTOS: A hanseníase persiste como problema de saúde pública, e episódios de ENH são eventos agudos que ocorrem antes, durante e após PQT. Na última década, o uso da talidomida como agente imunomodulador foi expandido a outras doenças. OBJETIVOS: realizar revisão sistemática dos ensaios clínicos publicados sobre a eficácia e efeitos colaterais da talidomida no ENH. Descrever metodologia e resultados da triagem para recrutamento de ensaio clínico visando avaliar dose-resposta da talidomida seguida de desmame no ENH moderado e grave, realizado no Brasil. MÉTODOS: Analisaram-se ensaios publicados sobre talidomida no ENH. Foi delineado um ensaio clínico duplo-cego randomizado para avaliar dose de 100 thalid 300mg/dia de talidomida durante fase aguda de ENH, seguida de desmame da talidomida, thalid placebo. Para este ensaio clínico descreve-se metodologia e dados de recrutamento de pacientes, com ênfase na gravidade dos episódios de ENH. RESULTADOS: Os seis ensaios clínicos publicados nas décadas de 1960 e 1970 apontam para o benefício da talidomida no ENH, embora diferenças metodológicas dificultem a comparação. Na fase de recrutamento do ensaio brasileiro, dos 143 pacientes de ENH triados, 65% eram potencialmente elegíveis. A associação com neurite em 56,4% dos ENH moderados e graves exigiu co-intervenção com corticosteróide. CONCLUSÃO: O padrão de recrutamento dos pacientes evidenciou alta freqüência de neurite nos episódios de ENH. O esquema de talidomida isolada no ENH foi avaliado como infreqüente na prática clínica brasileira. O desafio atual é acumular evidências sobre a eficácia e efeitos colaterais da talidomida em associação com corticosteróides.BACKGROUND: Leprosy remains a public health problem. Episodes of erythema nodosum leprosum (ENL) are acute events that occur before, during and after polychemotherapy. In the last decade, the use of thalidomide as an immunomodulating agent was expanded to other diseases. OBJECTIVES: To perform a systematic review of published clinical trials on efficacy and side effects of thalidomide in ENL. To describe the methodology and screening results of recruiting for a clinical trial performed in Brazil, which aimed to assess the dose-response of thalidomide followed by tapering regimen in severe and moderate cases of ENL. METHODS: Published clinical trials on the use of thalidomide in ENL were analyzed. A randomized, double-blind clinical trial was designed to evaluate the doses of 100mg versus 300mg/day thalidomide during the acute stage of ENL, followed by thalidomide tapering regimen versus placebo. For this clinical trial, the methodology and data for enrollment of patients were described, with an emphasis on severity of ENL episodes. RESULTS: Six clinical trials published in the 1960's and 1970's indicated the benefits of thalidomide in ENL, although methodological differences made comparison difficult. In the enrollment stage of the Brazilian trial, 65% of patients were potentially eligible out of 143 ENL patients screened. The association with neuritis in 56.4% of moderate and severe cases of ENL required the co-intervention with steroids. CONCLUSION: The patients' enrollment pattern demonstrated high frequency of neuritis in ENL episodes. The treatment regimen with thalidomide in monotherapy for ENL was considered infrequent in the clinical practice in Brazil. The current challenge is to accumulate evidence about efficacy and side effects of thalidomide in combination with steroids

An investigation into applicability of TQM to audit firms in Singapore.

Quality is a major factor for achieving commercial success. A quality culture that permeates the entire company constitutes competitive edge in the present-day-business arena. Increasing emphasis on quality has Ied to the spread ofimerest in Total Quality Management (TQM) as a way of improving company’s quality standard. With a more discerning market-place, TQM has gone beyond being just a phenomenon. Now, it is a movement spreading from production-oriented organisations to the service industry in Singapore. Despite its importance and diffusion in the service industry, it is not known how extensively TQM is embraced by local audit firms. No empirical studies have been conducted to analyze the development ofTQM in audit firms in Singapore. This research study is therefore undertaken to fill this void in the literature by providing an exploratory study on the development ofTQM in local audit firms. The research methodology for this Applied Research Project relies primarily on interviews and a questionaire survey, featuring questions pertaining to the practice of TQM principles among audit firms and their understanding and perceptions of TQM. The investigations seem to indicate that audit firms do have a Quality Management system. The evidence ofthe study seems to suggest that local audit firms are not lacking in the commitment to TQM procedures. The issue of feasibility of obtaining ISO 9000 certification was also investigated and the survey findings indicate a general consensus among the respondents that the benefit does not justify the cost of pursuing ISO 9000 certification. Future directions for research on this topic are highlighted at the end ofthe study.ACCOUNTANC

Fatores de risco e prevenção das lesões musculoesqueléticas em praticantes de corrida. Revisão de literatura

Introdução: Uma das conseqüências da popularização da corrida é o aumento das lesões entre os adeptos. Entender os fatores de é importante para que sejam tomadas medidas preventivas. Objetivo: Realizar uma revisão a respeito dos principais fatores de risco e prevenção de lesões musculoesqueléticas em corredores. Metodologia: Constitui­se de uma revisão da literatura onde foi realizada consulta a livros e artigos científicos pesquisados nos bancos de dados do Google acadêmico e Scielo. Resultado: Dentre os principais fatores de risco está a má periodização, dor, pisada irregular, aumento do ângulo Q, desigualdade estrutural de membros inferiores, fatores biomecânicos associados com lesões, pisos irregulares e calçados. Avaliação, treinamento periodizado e manutenção dos níveis de segurança são fundamentais para prevenir e diminuir os riscos de lesão em corredores. Conclusão: Conhecer as causas que levam ao aumento da incidência de lesão desportiva é fundamental para adotar medidas preventivas.Introduction: A consequence of the popularization of the race is the increase in injuries among fans. Understanding the factors is important so that preventive measures are taken. Objective: To review about the main risk factors and prevention of musculoskeletal injuries in runners. Methodology: It consists of a literature review which was carried out consulting books and scientific papers researched on the banks of the Google Scholar and Scielo. Results: Among the main risk factors is poor periodization, pain, irregular trampled, increased Q angle, structural inequality of the lower limbs, biomechanical factors associated with injuries, uneven floors and shoes. Evaluation, periodized training and maintenance of security levels are critical to prevent and reduce the risk of injury in runners. Conclusion: Knowing the causes that lead to increased incidence of sports injury is essential to adopt preventive measures

Myocardial Infarction Across COVID‐19 Pandemic Phases: Insights From the Veterans Health Affairs System

Background Cardiovascular procedural treatments were deferred at scale during the COVID‐19 pandemic, with unclear impact on patients presenting with non–ST‐segment–elevation myocardial infarction (NSTEMI). Methods and Results In a retrospective cohort study of all patients diagnosed with NSTEMI in the US Veterans Affairs Healthcare System from January 1, 2019 to October 30, 2022 (n=67 125), procedural treatments and outcomes were compared between the prepandemic period and 6 unique pandemic phases: (1) acute phase, (2) community spread, (3) first peak, (4) post vaccine, (5) second peak, and (6) recovery. Multivariable regression analysis was performed to assess the association between pandemic phases and 30‐day mortality. NSTEMI volumes dropped significantly with the pandemic onset (62.7% of prepandemic peak) and did not revert to prepandemic levels in subsequent phases, even after vaccine availability. Percutaneous coronary intervention and coronary artery bypass grafting volumes declined proportionally. Compared with the prepandemic period, patients with NSTEMI experienced higher 30‐day mortality during Phases 2 and 3, even after adjustment for COVID‐19‐positive status, demographics, baseline comorbidities, and receipt of procedural treatment (adjusted odds ratio for Phases 2 and 3 combined, 1.26 [95% CI, 1.13–1.43], P<0.01). Patients receiving Veterans Affairs‐paid community care had a higher adjusted risk of 30‐day mortality compared with those at Veterans Affairs hospitals across all 6 pandemic phases. Conclusions Higher mortality after NSTEMI occurred during the initial spread and first peak of the pandemic but resolved before the second, higher peak—suggesting effective adaptation of care delivery but a costly delay to implementation. Investigation into the vulnerabilities of the early pandemic spread are vital to informing future resource‐constrained practices

Association of insurance type with receipt of oral anticoagulation in insured patients with atrial fibrillation: A report from the American college of cardiology NCDR PINNACLE registry

Background: It is poorly understood whether insurance type may be a major contributor to the underuse of oral anticoagulation (OAC) among patients with atrial fibrillation (AF), particularly for novel oral anticoagulants (NOACs). Methods: We performed a retrospective cohort registry study of patients with insurance, AF, CHA2DS2-VASc ≥2, and at least one outpatient encounter recorded in the ACC NCDR\u27s PINNACLE Registry between January 1, 2011 and December 31, 2014. We used hierarchical regression, adjusting for patient characteristics and clustering by physician, to evaluate the association of insurance type (Private, Military, Medicare, Medicaid, Other) with receipt of OAC (any OAC, warfarin, or NOAC). Results: In 363,309 patients (age 75±10; 48% female), we found a significant difference in proportions of OAC and NOAC prescription across insurance types (OAC: Military 53%, Private 53%, Medicare 52%, Other 41%, Medicaid 41%, P\u3c.001; NOAC: Military 24%, Private 19%, Medicare 17%, Other 17%, Medicaid 8%, P\u3c.001). After adjustment for patient characteristics and facility, private, Medicaid, and other insurance were independently associated with a lower odds of OAC prescription relative to Medicare, but military insured patients were not significantly different. After adjustment, military and private insurance were independently associated with a higher odds of NOAC prescription relative to Medicare, while Medicaid and other insurance were associated with a lower odds of NOAC prescription. Conclusions: In a contemporary US AF population, there was significant variation of OAC prescription across insurance plans, with the highest among private and Medicare insured patients. These differences may indicate that insurance plan, and its associated pharmacy benefits, affect the pace of diffusion of new therapie

Cardiovascular Procedural Deferral and Outcomes over COVID-19 Pandemic Phases: A Multi-Center Study.

BACKGROUND: The COVID-19 pandemic has disrupted routine cardiovascular care, with unclear impact on procedural deferrals and associated outcomes across diverse patient populations. METHODS: Cardiovascular procedures performed at 30 hospitals across six Western states in two large, non-profit healthcare systems (Providence St. Joseph Health and Stanford Healthcare) from December 2018-June 2020 were analyzed for changes over time. Risk-adjusted in-hospital mortality was compared across pandemic phases with multivariate logistic regression. RESULTS: Among 36,125 procedures (69% percutaneous coronary intervention, 13% coronary artery bypass graft surgery, 10% transcatheter aortic valve replacement, and 8% surgical aortic valve replacement), weekly volumes changed in two distinct phases after the initial inflection point on February 23, 2020: an initial period of significant deferral (COVID I: March 15 to April 11) followed by recovery (COVID II: April 12 onwards). Compared to pre-COVID, COVID I patients were less likely to be female (p=0.0003), older (p CONCLUSIONS: Significant decreases in cardiovascular procedural volumes occurred early in the COVID-19 pandemic, with disproportionate impacts by race, gender, and age. These findings should inform our approach to future healthcare disruptions

Intravascular lithotripsy for the treatment of severely calcified coronary artery disease: A DISRUPT CAD III intravascular ultrasound substudy

BACKGROUND: Coronary intravascular lithotripsy (IVL) has emerged as a novel technique for the treatment of severely calcified coronary lesions. We evaluated the mechanism and efficacy of IVL in facilitating optimal stent implantation in heavily calcified coronary lesions using intravascular ultrasound (IVUS). METHODS: Forty-six patients were initially enrolled as a part of the Disrupt CAD III study. Of these, 33 had pre-IVL, 24 had post-IVL, and 44 had post-stent IVUS evaluation. The final analysis was performed on 18 patients who had IVUS images interpretable at all three intervals. The primary endpoint was increase in minimum lumen area (MLA) from pre-IVL to post-IVL treatment to post-stenting. RESULTS: Pre-IVL, MLA was 2.75 ± 0.84 mm(2), percent area stenosis was 67.22 % ± 20.95 % with maximum calcium angle of 266.90° ± 78.30°, confirming severely calcified lesions. After IVL, MLA increased to 4.06 ± 1.41 mm(2) (p = 0.0003), percent area stenosis decreased to 54.80 % ± 25.71 % (p = 0.0009), and maximum calcium angle decreased to 239.40° ± 76.73° (p = 0.003). There was a further increase in MLA to 6.84 ± 2.18 mm(2) (p \u3c 0.0001) and decrease in percent area stenosis to 30.33 % ± 35.08 % (p \u3c 0.0001) post-stenting with minimum stent area of 6.99 ± 2.14 mm(2). The success rate of stent delivery, implantation, and post-stent dilation was 100 % post-IVL. CONCLUSION: In this first study evaluating the mechanism of IVL using IVUS, the primary endpoint of increase in MLA from pre-IVL to post-IVL treatment to post-stenting was successfully achieved. Our study showed that the use of IVL-assisted percutaneous coronary intervention is associated with improved vessel compliance, facilitating optimal stent implantation in de novo severely calcified lesions