Loss of helicase C-terminal domain of SMARCAL1 protein associated with severe Schimke immuno-osseous dysplasia.

Schimke immuno-osseous dysplasia (SIOD) is a rare multi-system condition caused by biallelic loss-of-function mutations in the SMARCAL1 gene. This disorder is characterized by disproportionate growth failure, T-cell deficiency, and renal dysfunction. Pathogenic variants in the SMARCAL1 gene have been reported in only approximately half of SIOD-affected individuals. Among these alterations, nonsense and frameshift mutations generally lead to a severe phenotype with early onset. In this study, we identified novel mutations in an Iranian patient with SIOD. A 4-year-old girl with developmental delay and facial dysmorphism was referred to our center for molecular diagnosis. We applied whole-exome and Sanger sequencing for co-segregation analysis. Subsequently, bioinformatic analysis was performed to assess the pathogenic effects of the variants and their post-transcriptional effects. We discovered two novel mutations (c.2281delT and c.2283delA) in exon 15 of the SMARCAL1 gene, resulting in a truncated protein with a loss of 193 amino acids (p.S761Rfs*1). Variant effect predictors indicated that these variants are pathogenic, and multi-sequence alignments revealed high conservation of this region among different species. Given that our patient exhibited severe a phenotype and passed away soon after receiving a definitive molecular diagnosis, we propose that the loss of the helicase C-terminal domain in the deleted part of SMARCAL1 may lead to the severe form of SIOD. Besides, the combination of growth retardation and bone abnormalities also plays a crucial role in the early diagnosis of the disease.

Relationship Between Patient Activation and Type 2 Diabetes Mellitus Self-management and Clinical Outcomes in Saudi Arabian Primary Care Setting.

PURPOSE: Type 2 diabetes mellitus (T2DM) self-management is a comprehensive approach that individuals with T2DM employ to manage and control their condition. Patients' activation, "an individual's knowledge, skill, and confidence for managing their health and health care", has been used as a major driver of self-management. This study aimed to assess the relationship of patient activation with T2DM self-management and clinical outcomes. DESIGN: A cross-sectional study. SUBJECTS: Patients with type T2DM who age 18-years and older. SETTING: The primary care centers in Saudi Arabia. MEASURES: Patient activation measure (PAM) and the Summary of Diabetes Self-Care Activities (SDSCA). ANALYSIS: Descriptive statistic, T-test, One-way ANOVA test, Chi-square test, and linear and logistic regressions were performed. RESULTS: A total of 398 patients, mostly male (54.9%) with a mean age of 53.2 (±10.7) years old participated in the study. The participants' mean of Hemoglobin A1c (HbA1c) was 8.4% (±1.7%) and most of them (74.5%) had an uncontrolled HbA1c level (>7% %). The mean patient activation score was 55.9 (±13.5). 24.4% were at [PA1], 26.7% at [PA2], 37.4% at [PA3], and 11.5% at [PA4]. Patient activation level was positively associated with better glycemic control and self-management behaviors including diet, physical activity, blood glucose self-testing, foot care, and smoking (P < .05) but not with adherence to medication. CONCLUSIONS: Our findings reveal a positive association between patient activation level and enhanced glycemic control and self-management behaviors and suggest that patient activation-informed self-management interventions are more likely to yield promising health outcomes.

Does Geography Play a Role in the Receipt of End-of-Life Care for Advanced Cancer Patients? Evidence from an Australian Local Health District Population-Based Study.

Objectives: To assess the influence of geographic remoteness on health care utilization at end of life (EOL) by people with advanced cancer in a geographically diverse Australian local health district, using two objective measures of rurality and travel-time estimations to health care facilities. Methods: This retrospective cohort study examined the association between rurality (using the Modified Monash Model) and travel-time estimation, and demographic and clinical factors, with the receipt of >1 inpatient and outpatient health service in the last year of life in multivariate models. The study cohort comprised of 3546 patients with cancer, aged ≥18 years, who died in a public hospital between 2015 and 2019. Results: Compared with decedents from metropolitan areas, decedents from some rural areas had higher rates of emergency department visits (small rural towns: aRR 1.29, 95% CI: 1.07-1.57) and ICU admissions (large rural towns: aRR 1.32, 95% CI: 1.03-1.69), but lower rates of acute hospital admissions (large rural towns: aRR 0.83, 95% CI: 0.76-0.90), inpatient palliative care (PC) (regional centers: aRR 0.85, 95% CI: 0.75-0.97), and inpatient radiotherapy (lowest in small rural towns: aRR 0.07, 95% CI: 0.03-0.18). Decedents from rural and regional centers had lower rates of outpatient chemotherapy and radiotherapy use, yet higher rates of outpatient cancer service utilization (p < 0.05). Shorter travel times (10-<30 minutes) were associated with higher rates of inpatient specialist PC (aRR 1.48, 95% CI: 1.09-1.98). Conclusions: Reporting on a series of inpatient and outpatient services used in the last year of life, measures of rurality and travel-time estimates can be useful tools to estimate geographic variation in EOL cancer care provision, with significant gaps uncovered in inpatient PC and outpatient service utilization in rural areas. Policies aimed at redistributing EOL resources in rural and regional communities to reduce travel times to health care facilities could help to reduce regional disparities and ensure equitable access to EOL care services.

Challenges and strategies to improve the provision of end-of-life cancer care in rural and regional communities: Perspectives from Australian rural health professionals.

OBJECTIVE: To identify challenges and strategies to improve the provision of end-of-life (EOL) cancer care in an underserved rural and regional Australian local health district (LHD) from the perspective of general practitioners (GPs) and specialist clinicians while exploring the benefits of adopting a generalist health care approach to delivering EOL care in rural and regional communities. SETTING: Rural and regional Australia. PARTICIPANTS: General practitioners and palliative care and cancer care specialists (medical and nursing) involved in the provision of EOL care to people with advanced cancer in the rural and regional areas of an Australian LHD. DESIGN: Qualitative descriptive study involving 22 participants in four face-to-face and online focus groups. Thematic analysis of the transcripts identified key issues affecting EOL care for people with advanced cancer in rural and regional areas of the LHD. RESULTS: Four themes including geographical remoteness, system structures, medical management and expertise and training emerged from the focus groups. Key barriers to effective EOL care included insufficient remuneration for GPs and other clinicians (especially home visits), resource limitations, limited community awareness of palliative care and lack of confidence and training of clinicians. Continuity of care was identified as an important facilitator to effective EOL care. Participants suggested greater Medicare rebates for palliative care and home visits, adequate equipment and resources, technology-enabled clinician training and greater rural-based training for specialist PC clinicians may improve the provision of EOL care in regional and rural communities. CONCLUSIONS: Rural-based clinicians delivering EOL cancer care appear to be disproportionately affected by geographical challenges including resource and funding limitations. A multi-pronged strategy aimed at greater interdisciplinary collaboration, community awareness and greater resourcing and funding could help to improve the provision of EOL care in underserved rural and remote communities of Australia.

Application of Artificial Intelligence in Assessing the Self-Management Practices of Patients with Type 2 Diabetes.

The use of Artificial intelligence in healthcare has evolved substantially in recent years. In medical diagnosis, Artificial intelligence algorithms are used to forecast or diagnose a variety of life-threatening illnesses, including breast cancer, diabetes, heart disease, etc. The main objective of this study is to assess self-management practices among patients with type 2 diabetes in rural areas of Pakistan using Artificial intelligence and machine learning algorithms. Of particular note is the assessment of the factors associated with poor self-management activities, such as non-adhering to medications, poor eating habits, lack of physical activities, and poor glycemic control (HbA1c %). The sample of 200 participants was purposefully recruited from the medical clinics in rural areas of Pakistan. The artificial neural network algorithm and logistic regression classification algorithms were used to assess diabetes self-management activities. The diabetes dataset was split 80:20 between training and testing; 80% (160) instances were used for training purposes and 20% (40) instances were used for testing purposes, while the algorithms' overall performance was measured using a confusion matrix. The current study found that self-management efforts and glycemic control were poor among diabetes patients in rural areas of Pakistan. The logistic regression model performance was evaluated based on the confusion matrix. The accuracy of the training set was 98%, while the test set's accuracy was 97.5%; each set had a recall rate of 79% and 75%, respectively. The output of the confusion matrix showed that only 11 out of 200 patients were correctly assessed/classified as meeting diabetes self-management targets based on the values of HbA1c < 7%. We added a wide range of neurons (32 to 128) in the hidden layers to train the artificial neural network models. The results showed that the model with three hidden layers and Adam's optimisation function achieved 98% accuracy on the validation set. This study has assessed the factors associated with poor self-management activities among patients with type 2 diabetes in rural areas of Pakistan. The use of a wide range of neurons in the hidden layers to train the artificial neural network models improved outcomes, confirming the model's effectiveness and efficiency in assessing diabetes self-management activities from the required data attributes.

Lung Cancer and Self-Management Interventions: A Systematic Review of Randomised Controlled Trials.

Background: Lung cancer is the most common cancer worldwide. Evidence suggests self-management (SM) interventions benefit cancer patients. This review aims to determine the effectiveness of SM interventions for lung cancer patients. Method: Searches occurred in PubMed, Cinahl, ProQuest, Psych Info, Scopus, and Medline, using predefined criteria, assessing randomised controlled trials (RCTs). Results: Five hundred and eighty-seven studies were yielded, 10 RCTs met criteria. Of the total patient pool, 1001 of 1089 had Non-Small Cell Lung Cancer (NSCLC). Six studies tested home-based SM exercise, two studies SM education, and one each for diary utilisation and symptom reporting. Fatigue was the most targeted function. Other functions targeted included exercise capacity, anxiety, depression, quality of life (QoL), sleep quality, and symptom burden. Six studies met their primary endpoints (five SM exercise, one SM education). Positive outcomes are described for fatigue, anxiety/depression, sleep quality, self-efficacy, and exercise capacity. With exception to fatigue, early-stage NSCLC, younger age, female, never smokers, partnered patients experienced increased treatment effect. Conclusions: SM interventions improve outcomes among some lung cancer patients. Interventions targeting fatigue yield benefit despite histology, stage or gender and could encourage broader cohort engagement. Consideration of patient characteristics may predict SM effect. Effectiveness of home-based SM exercise by NSCLC stage and SM tailored to sociodemographic variables requires further research.

Association between e-cigarette use and asthma: a systematic review and meta-analysis.

OBJECTIVE: Increasing e-cigarette use combined with emerging evidence of their respiratory effects raises concerns about their potential impact on asthma prevalence. This review evaluates the most recent available evidence on the association of e-cigarette use and asthma world-wide. METHODS: A literature search was performed in PubMed, Scopus, CINAHL, Cochrane Library, Web of Science and ProQuest in March 2021. This study was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) registered with PROSPERO (registration number: CRD42020211812). STUDY SELECTIONS: Cross-sectional and cohort studies assessing the association between e-cigarette use and asthma were eligible for inclusion. Studies examining exacerbations in asthma symptoms and severity were excluded. The quality of the included studies was assessed using the Appraisal tool for Cross-Sectional Studies (AXIS). RESULTS: Thirteen cross-sectional studies with the sample size of 1,039,203 met the eligibility criteria. Odds ratios were pooled using a random effects model. Pooled analysis found a significant association between current e-cigarette use and asthma (pOR = 1.36, 95% CI 1.21-1.52) and ever e-cigarette use and asthma (pOR = 1.24 95% CI 1.13-1.36). CONCLUSION: Our review found that e-cigarette use and ever e-cigarette use are correlated with asthma. However, heterogeneity and inconsistencies between covariates limited the interpretation of the results. This warrants further studies to investigate any potential causal association between e-cigarette use and asthma. No funding was received for this systematic review.

Effectiveness of Health Literacy Interventions on COPD Self-Management Outcomes in Outpatient Settings: A Systematic Review.

Chronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease which imposes significant health and economic burdens on societies. Self-management is beneficial in controlling and managing COPD and health literacy (HL) is a major driver of COPD self-management. This review aims to summarize the most recent evidence on the effectiveness of HL driven COPD self-management interventions using randomized controlled trials (RCTs). Eight data bases including Science Citation Index, Academic Search Complete, Social Sciences Citation Index, CINAHL Plus, APA PsycInfo, MEDLINE, Scopus and ScienceDirect were searched to find eligible RCTs assessing the effectiveness of HL interventions on COPD self-management outcomes in outpatient settings between 2008 and February 2020. Ten RCTs met the eligibility criteria. The review found that HL interventions led to moderate improvements in physical activity levels (four out of seven trials) and COPD knowledge (three out of six trials). Surprisingly, none of the RCTs led to significant improvement in medication adherence, which warrants further studies. Furthermore, there were inconclusive findings regarding other COPD self-management outcomes such as smoking cessation, medication adherence, dyspnea, mental health, hospital admissions and health related quality of life.

End-of-Life Cancer Care Resource Utilisation in Rural Versus Urban Settings: A Systematic Review.

BACKGROUND: Despite the advances in End-of-life (EOL) cancer care, disparities remain in the accessibility and utilisation of EOL cancer care resources. Often explained by socio-demographic factors, geographic variation exists in the availability and provision of EOL cancer care services among EOL cancer decedents across urban versus rural settings. This systematic review aims to synthesise mortality follow-back studies on the patterns of EOL cancer care resource use for adults (>18 years) during end-of-life cancer care. METHODS: Five databases were searched and data analysed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria involved; a) original research; b) quantitative studies; c) English language; d) palliative care related service use in adults (>18 years) with any malignancy excluding non-melanoma skin cancers; e) exclusive end of life focus; f) urban-rural focus. Narrative reviews and discussions were excluded. RESULTS: 24 studies met the inclusion criteria. End-of-life cancer care service utilisation patterns varied by rurality and treatment intent. Rurality was strongly associated with higher rates of Emergency Department (ED) visits and hospitalisations and lower rates of hospice care. The largest inequities between urban and rural health service utilisation patterns were explained by individual level factors including age, gender, proximity to service and survival time from cancer diagnosis. CONCLUSIONS: Rurality is an important predictor for poorer outcomes in end-of-life cancer care. Findings suggest that addressing the disparities in the urban-rural continuum is critical for efficient and equitable palliative cancer care. Further research is needed to understand barriers to service access and usage to achieve optimal EOL care for all cancer patient populations.

The Role of Health Literacy on the Self-Management of Chronic Obstructive Pulmonary Disease: A Systematic Review.

The effects of health literacy in developing self-management skills among people suffering from Chronic Obstructive Pulmonary Disease (COPD) is a topic that has been lightly tread upon. The advent of tobacco smoking and air pollution caused by the industrialisation era has caused a startling increase in the rates of incidence and prevalence of those diagnosed with COPD. Despite advancement in medical treatment, prevention and health care systems COPD poses a great challenge to public health now than ever before. This systematic review examines eight articles that have dealt with the role health literacy plays in developing self-management skills. This study found that there is no relationship between the adequacy of health literacy and the knowledge or learning of a self-management skill. The relationship between heath literacy and developing skills such as correct technique of inhaler use, awareness of an exacerbation, usage of home-based technological support (telehomecare) needs further delving. Remarkably, it also revealed that health literacy sensitive materials improved self-management skills in all the levels of health literacy. More research is required in identifying literacy sensitive methods that would be beneficial to all disregarding of the level health literary. A wider range of self-management skills pertaining to prevention, maintenance and control needs to be explored.

RUNX1 variant as a genetic predisposition factor for acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common hematological malignancy among adults and is characterized by accumulation of immature myeloid cells. Different genetic factors have role in the occurrence of AML. Among different proteins, RUNX1 and BAALC are involved in the development AML. It has been shown that BAALC overexpression is a factor that indicate shorter disease free survival in a subset of AML patients. RUNX1 has been implicated in the development of breast, prostate, lung, and skin cancers. The aim of this study is determination of the prevalence of common polymorphisms in BAALC (rs6999622 and rs62527607) and RUNX1 (rs13051066 and rs61750222) in AML patients compared with healthy subjects. A total of 100 AML patients and 100 healthy control subjects were included in our study. Genomic DNA was isolated from peripheral blood and the polymorphisms were genotyped by applying ARMS and PCR-RFLP methods. Finally, data was analyzed using SPPSS software. Our results demonstrate a significant association between the RUNX1 rs13051066 and AML in the co-dominant (odd ratio = 6.66, 95% Cl = 1.85-25, p = .006) and dominant (GT + TT versus GG: odd ratio = 6.15, 95% CI = 1.73-21.87, p = .002) models. The RUNX1 rs13051066 polymorphism is associated with risk of AML in Iranian population. Future studies should consider larger sample size for assessment of RUNX1 gene polymorphisms, and employ cytogenetic and molecular analyses in AML patients from different ethnic origins.

Dual biomarkers long non-coding RNA GAS5 and its target, NR3C1, contribute to acute myeloid leukemia.

Acute myeloid leukemia (AML) is a complex hematological neoplasm with poor prognosis. At present, overwhelming evidence indicates that different genetic abnormalities are relevant to the pathogenesis of AML. Nevertheless, its exact molecular mechanism is still unknown. Recently, it was reported that lncRNAs play crucial roles in tumorigenesis. But, their role in the molecular pathogenesis of AML has not been extensively explored. GAS5, one of the earliest known lncRNAs, has an essential role in the formation and progression of multiple human cancers. It was recently demonstrated that GAS5 acts as a riborepressor of the Glucocorticoid receptor) GR) and abnormal levels of GAS5 may alter response of hematopoietic cells to glucocorticoids. GAS5 can have interaction with the GR that encoded by NR3C1 gene and inhibit its transcriptional activity. To test whether the genetic variants can be associated with AML risk, we genotyped rs55829688 (T > C) polymorphism in GAS5 and three NR3C1 SNPs namely rs6195, rs41423247 and rs6189/rs6190 in a population of 100 Iranian AML patients and 100 healthy subjects. The analysis of the data showed the frequency of alleles and genotypes of rs55829688 and rs6189/rs6190 polymorphisms did not differ between patients and healthy subjects. But, rs41423247 and rs6195 demonstrated a significant correlation with AML risk. The rs6195 was associated with higher AML susceptibility in the co-dominant (OR = 4.58, 95% CI = 2.11-9.981, P < .0001), dominant (OR = 4.55, 95% CI = 2.155-9.613, P < .0001), and over-dominant (OR = 4.43, 95% CI = 2.042-9.621, P < .0001) models. Also, the rs41423247 polymorphism was associated with higher risk of AML in co-dominant (OR = 2.07, 95% CI = 1.171-4.242, P = .012) and dominant (OR = 2.47, 95% CI = 1.192-5.142, P = .010) models. Furthermore, haplotype analysis (rs41423247, rs6189.rs6190, rs6195, and rs55829688 respectively) demonstrated that GGAT, CGGT, and GGGT haplotypes were associated with higher risk of AML in the studied population (p-values = .007, 0.042 and 0.044, respectively). The present study reveals a possible role for NR3C1 in the pathogenesis of AML.

Effectiveness of chronic obstructive pulmonary disease self-management interventions in primary care settings: a systematic review.

Chronic obstructive pulmonary disease (COPD) is one of the more disabling diseases and the third cause of mortality worldwide. Self-management is considered an effective strategy for controlling and managing COPD. This review aims to summarise the available evidence on the effectiveness of COPD self-management in primary care settings. Social Sciences, Citation Index, MEDLINE, CINAHL, Academic Search Complete and Scopus were searched for randomised controlled trials of COPD self-management in general practice between 2001 and 2018. Ten randomised controlled trials of COPD self-management trials conducted in primary care settings were included in this review. The identified trials have recruited stable patients; a majority having mild to moderate COPD. The trials implemented different types of interventions and measured improvements in knowledge, skills and behaviours of self-management, mental health, self-efficacy and endpoint outcomes such as hospitalisation and quality of life. The findings showed that COPD self-management trials had positive effects on COPD knowledge and improved self-management behaviours such as adherence to medication, physical activities and smoking cessation in some cases; however, the effect of trials on hospitalisation rate, quality of life and healthcare utilisation were not conclusive. There was also not enough evidence to suggest that the trials were efficient in improving self-efficacy, a major driver of self-management behaviours. Primary care COPD self-management trials are efficient in improving surrogate outcomes such as knowledge of and adherence to self-management behaviours; however, such improvements are less likely to be sustainable in the absence of self-efficacy. Future studies should also focus on improving endpoint self-management outcomes like hospitalisation rate and quality of life to benefit both patient and healthcare system.

Nutritional assessment and factors associated with malnutrition among the elderly population of Nepal: a cross-sectional study.

OBJECTIVES: This study aimed at assessing the nutritional status among the elderly population and factors associated with malnutrition in the community setting in rural Nepal. RESULTS: Out of 339 participants, 24.8% (95% CI 20.21-29.30) fell into the normal nutritional status range; 49.6% (95% CI 44.29-54.91) were at risk for malnutrition while 24.8% (95% CI 20.21-29.30) were in the malnourished range, based on Mini Nutritional Assessment scores. Our findings revealed that belonging to a Dalit community, being unemployed, having experience of any form of mistreatment, lack of physical exercise, experiencing problems with concentration in past 30 days and taking medication for more than one co-morbidity was significantly associated with the malnutrition status of the elderly.

Inter/intra-observer reproducibility of Gleason scoring in prostate adenocarcinoma in Iranian pathologists.

PURPOSE: To measure the level of inter/intra-observer reproducibility among pathologists as far as Gleason scoring of adenocarcinoma of the prostate is concerned. MATERIALS AND METHODS: A total of 101 prostate biopsy slides, diagnosed with adenocarcinoma of the prostate by five pathologists from different education centers, were exposed to Gleason scoring. Two months later, the slides were re-examined by three of the same pathologists. Thereafter, the kappa was calculated for the data provided in the first and second reports of each pathologist and compared between pathologists. RESULTS: Inter-observer reproducibility was inappropriate, but intra-observer diagnostic reproducibility was almost perfect with a corresponding percentage of agreement of 85.2%. CONCLUSION: The inter-observer reproducibility was poor.