Improved Side Effect Profile of Alternate-Day Dosing of Lenalidomide.

Myelodysplastic syndrome (MDS) is a heterogeneous hematological condition associated with cytopenia, inadequate blood cell synthesis, and the risk of developing acute myeloid leukemia (AML). Patients are divided into risk groups according to the International Prognostic Scoring System (IPSS) to help direct therapy. Allogeneic stem cell transplantation, despite its limitations, is curative. Medical management, such as the use of lenalidomide, has potential benefits but can cause adverse effects that require dose regimen modification. Lenalidomide is approved for low-risk MDS with 5q deletion (5q- MDS). In this case study, a 79-year-old woman with 5q- MDS was switched from a daily regimen to an alternate-day lenalidomide dose schedule to achieve complete remission with fewer adverse effects. The management of hematological toxicity and the mechanisms of action of lenalidomide are discussed. We recommend individualized treatment strategies and additional research to improve MDS management.

Active Case Finding for Tuberculosis in Migrants: a Systematic Review.

Background: Active case finding (ACF) is an alternative strategy to accelerate the identification of TB cases among the migrant population. Objective: This study aimed to synthesize the evidence for the effectiveness of ACF TB in migrants. Methods: This study uses the PRISMA model as a method of searching for journal articles in the databases of Google Scholar, ProQuest, EBSCO, ScienceDirect, Elsevier, and PubMed, as well as other sources such as textbooks and reports from 2017 to 2021 with the keywords "tuberculosis" AND "active case finding" AND "migrant". The search revealed 371 articles, of which 26 met the criteria for further discussion. Results: Most studies show that the TB incidence among migrants is higher than in the local population. Factors leading to increased cases include lack of knowledge about the symptoms, high mobilization, social isolation, economic problems, and medication adherence that impact an advanced stage. Furthermore, it is also influenced by the low quality of health services, including accessibility, health facilities, health workers, and information. Therefore, Active Case Finding (ACF) is more effective in identifying cases of TB in the risk groups. This was conducted on migrants with increased notifications followed up with treatment. Conclusion: ACF is effective approach in screening and diagnosing TB in the migrant group.

Unsupervised item response theory models for assessing sample heterogeneity in patient-reported outcomes measures.

PURPOSE: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models. METHODS: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics. RESULTS: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease. CONCLUSION: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF.

Transitions between versions of the International Classification of Diseases and chronic disease prevalence estimates from administrative health data: a population-based study.

BACKGROUND: Diagnosis codes in administrative health data are routinely used to monitor trends in disease prevalence and incidence. The International Classification of Diseases (ICD), which is used to record these diagnoses, have been updated multiple times to reflect advances in health and medical research. Our objective was to examine the impact of transitions between ICD versions on the prevalence of chronic health conditions estimated from administrative health data. METHODS: Study data (i.e., physician billing claims, hospital records) were from the province of Manitoba, Canada, which has a universal healthcare system. ICDA-8 (with adaptations), ICD-9-CM (clinical modification), and ICD-10-CA (Canadian adaptation; hospital records only) codes are captured in the data. Annual study cohorts included all individuals 18 + years of age for 45 years from 1974 to 2018. Negative binomial regression was used to estimate annual age- and sex-adjusted prevalence and model parameters (i.e., slopes and intercepts) for 16 chronic health conditions. Statistical control charts were used to assess the impact of changes in ICD version on model parameter estimates. Hotelling's T2 statistic was used to combine the parameter estimates and provide an out-of-control signal when its value was above a pre-specified control limit. RESULTS: The annual cohort sizes ranged from 360,341 to 824,816. Hypertension and skin cancer were among the most and least diagnosed health conditions, respectively; their prevalence per 1,000 population increased from 40.5 to 223.6 and from 0.3 to 2.1, respectively, within the study period. The average annual rate of change in prevalence ranged from -1.6% (95% confidence interval [CI]: -1.8, -1.4) for acute myocardial infarction to 14.6% (95% CI: 13.9, 15.2) for hypertension. The control chart indicated out-of-control observations when transitioning from ICDA-8 to ICD-9-CM for 75% of the investigated chronic health conditions but no out-of-control observations when transitioning from ICD-9-CM to ICD-10-CA. CONCLUSIONS: The prevalence of most of the investigated chronic health conditions changed significantly in the transition from ICDA-8 to ICD-9-CM. These results point to the importance of considering changes in ICD coding as a factor that may influence the interpretation of trend estimates for chronic health conditions derived from administrative health data.

Extracellular expression in Bacillus subtilis of a thermostable Geobacillus stearothermophilus lipase

BACKGROUND The extracellular expression of enzymes in a secretion host such as Bacillus subtilis is a useful strategy in reducing the cost of downstream processing of industrial enzymes. Here, we present the first report of the successful extracellular expression in Bacillus subtilis WB800 of Geobacillus stearothermophilus lipase (T1.2RQ), a novel industriallydesirable thermostable lipolytic enzyme which has an excellent hydrolytic and transesterification activity. Signal peptides of a-amylase, extracellular protease, and lipase A, as well as two different promoters, were used in the secretion and expression of lipase T1.2RQ. RESULTS Lipase activity assay using p-nitrophenyl laurate showed that all three signal peptides directed the secretion of lipase T1.2RQ into the extracellular medium. The signal peptide of lipase A, resulted in the highest extracellular yield of 5.6 U/ml, which corresponds to a 6-fold increase over the parent Bacillus subtilis WB800 strain. SDS-PAGE and zymogram analysis confirmed that lipase T1.2RQ was correctly processed and secreted in its original size of 44 kDa. A comparison of the expression levels of lipase T1.2RQ in rich medium and minimal media showed that the enzyme was better expressed in rich media, with up to an 8-fold higher yield over minimal media. An attempt to further increase the lipase expression level by promoter optimization showed that, contrary to expectation, the optimized promoter exhibited similar expression levels as the original one, suggesting the need for the optimization of downstream factors. CONCLUSIONS The successful extracellular secretion of lipase T1.2RQ in Bacillus subtilis represents a remarkable feat in the industrial-scale production of this enzyme

Role of statin as inducer of Hmox-1 system in treatment of preeclampsia.

Preeclampsia is the major cause of both maternal and neonatal morbidity and mortality. Its insidence remains high and the management has not been established yet because its etiology and pathophysiological are still poorly understood. Theories regarding etiopathogenesis and management of preeclampsia have been postulated yet it remains controversial. Placental ischemic and angiogenic imbalance are suggested to be predisposing factors of preeclampsia. It is thereby targeted in prevention of preeclampsia. Unfortunately, both primary and secondary prevention using various supplements and drugs fails to exhibit good outcome. Overall, these efforts are considered useless. In recent years, researchers have been using statin derivative in management of preclampsia. It has been reported that statin provides protective effect in endothelial cells by inducing expression of Hmox-1 and inihibiting release of sFlt-1 as well as potent antioxidant properties. Thus, statin has been proposed as promising agent to significantly reduce anti-angiogenic in preeclamptic patients which is overviewed in this review based on recent studies.