The E592K variant of SF3B1 creates unique RNA missplicing and associates with high-risk MDS without ring sideroblasts.

Among the most common genetic alterations in the myelodysplastic syndromes (MDS) are mutations in the spliceosome gene SF3B1. Such mutations induce specific RNA missplicing events, directly promote ring sideroblast (RS) formation, and generally associate with more favorable prognosis. However, not all SF3B1 mutations are the same, and little is known about how distinct hotspots influence disease. Here we report that the E592K variant of SF3B1 associates with high-risk disease features in MDS, including a lack of RS, increased myeloblasts, a distinct co-mutation pattern, and a lack of the favorable survival seen with other SF3B1 mutations. Moreover, compared to other hotspot SF3B1 mutations, E592K induces a unique RNA missplicing pattern, retains an interaction with the splicing factor SUGP1, and preserves normal RNA splicing of the sideroblastic anemia genes TMEM14C and ABCB7. These data have implications for our understanding of the functional diversity of spliceosome mutations, as well as the pathobiology, classification, prognosis, and management of SF3B1-mutant MDS.

Large-scale RNA-seq mining reveals ciclopirox triggers TDP-43 cryptic exons.

Nuclear clearance and cytoplasmic aggregation of TDP-43 in neurons, initially identified in ALS-FTD, are hallmark pathological features observed across a spectrum of neurodegenerative diseases. We previously found that TDP-43 loss-of-function leads to the transcriptome-wide inclusion of deleterious cryptic exons in brains and biofluids post-mortem as well as during the presymptomatic stage of ALS-FTD, but upstream mechanisms that lead to TDP-43 dysregulation remain unclear. Here, we developed a web-based resource (SnapMine) to determine the levels of TDP-43 cryptic exon inclusion across hundreds of thousands of publicly available RNA sequencing datasets. We established cryptic exon inclusion across a variety of human cells and tissues to provide ground truth references for future studies on TDP-43 dysregulation. We then explored studies that were entirely unrelated to TDP-43 or neurodegeneration and found that ciclopirox olamine (CPX), an FDA-approved antifungal, can trigger the inclusion of TDP-43-associated cryptic exons in a variety of mouse and human primary cells. CPX induction of cryptic exon occurs via heavy metal toxicity and oxidative stress, suggesting that similar vulnerabilities could play a role in neurodegeneration. Our work demonstrates how diverse datasets can be linked through common biological features and underscores that public archives of sequencing data represent a vastly underutilized resource with tremendous potential for uncovering novel insights into complex biological mechanisms and diseases.

Podocyte number and glomerulosclerosis indices are associated with the response to therapy for primary focal segmental glomerulosclerosis.

Corticosteroid therapy, often in combination with inhibition of the renin-angiotensin system, is first-line therapy for primary focal and segmental glomerulosclerosis (FSGS) with nephrotic-range proteinuria. However, the response to treatment is variable, and therefore new approaches to indicate the response to therapy are required. Podocyte depletion is a hallmark of early FSGS, and here we investigated whether podocyte number, density and/or size in diagnostic biopsies and/or the degree of glomerulosclerosis could indicate the clinical response to first-line therapy. In this retrospective single center cohort study, 19 participants (13 responders, 6 non-responders) were included. Biopsies obtained at diagnosis were prepared for analysis of podocyte number, density and size using design-based stereology. Renal function and proteinuria were assessed 6 months after therapy commenced. Responders and non-responders had similar levels of proteinuria at the time of biopsy and similar kidney function. Patients who did not respond to treatment at 6 months had a significantly higher percentage of glomeruli with global sclerosis than responders (p < 0.05) and glomerulosclerotic index (p < 0.05). Podocyte number per glomerulus in responders was 279 (203-507; median, IQR), 50% greater than that of non-responders (186, 118-310; p < 0.05). These findings suggest that primary FSGS patients with higher podocyte number per glomerulus and less advanced glomerulosclerosis are more likely to respond to first-line therapy at 6 months. A podocyte number less than approximately 216 per glomerulus, a GSI greater than 1 and percentage global sclerosis greater than approximately 20% are associated with a lack of response to therapy. Larger, prospective studies are warranted to confirm whether these parameters may help inform therapeutic decision making at the time of diagnosis of primary FSGS.

Cross-linked enzyme aggregates of polyethylene terephthalate hydrolyse (PETase) from Ideonella sakaiensis for the improvement of plastic degradation.

Polyethylene terephthalate (PET) is one of the most produced plastics globally and its accumulation in the environment causes harm to the ecosystem. Polyethylene terephthalate hydrolyse (PETase) is an enzyme that can degrade PET into its monomers. However, free PETase lacks operational stabilities and is not reusable. In this study, development of cross-linked enzyme aggregate (CLEA) of PETase using amylopectin (Amy) as cross-linker was introduced to solve the limitations of free PETase. PETase-Amy-CLEA exhibited activity recovery of 81.9 % at its best immobilization condition. Furthermore, PETase-Amy-CLEA exhibited 1.37-, 2.75-, 2.28- and 1.36-fold higher half-lives than free PETase at 50 °C, 45 °C, 40 °C and 35 °C respectively. Moreover, PETase-Amy-CLEA showed broader pH stability from pH 5 to 10 and could be reused up to 5 cycles. PETase-Amy-CLEA retained >70 % of initial activity after 40 days of storage at 4 °C. In addition, lower Km of PETase-Amy-CLEA indicated better substrate affinity than free enzyme. PETase-Amy-CLEA corroded PET better and products yielded was 66.7 % higher than free PETase after 32 h of treatment. Hence, the enhanced operational stabilities, storage stability, reusability and plastic degradation ability are believed to make PETase-Amy-CLEA a promising biocatalyst in plastic degradation.

A fluid biomarker reveals loss of TDP-43 splicing repression in presymptomatic ALS-FTD.

Although loss of TAR DNA-binding protein 43 kDa (TDP-43) splicing repression is well documented in postmortem tissues of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), whether this abnormality occurs during early-stage disease remains unresolved. Cryptic exon inclusion reflects loss of function of TDP-43, and thus detection of proteins containing cryptic exon-encoded neoepitopes in cerebrospinal fluid (CSF) or blood could reveal the earliest stages of TDP-43 dysregulation in patients. Here we use a newly characterized monoclonal antibody specific to a TDP-43-dependent cryptic epitope (encoded by the cryptic exon found in HDGFL2) to show that loss of TDP-43 splicing repression occurs in ALS-FTD, including in presymptomatic C9orf72 mutation carriers. Cryptic hepatoma-derived growth factor-like protein 2 (HDGFL2) accumulates in CSF at significantly higher levels in familial ALS-FTD and sporadic ALS compared with controls and is elevated earlier than neurofilament light and phosphorylated neurofilament heavy chain protein levels in familial disease. Cryptic HDGFL2 can also be detected in blood of individuals with ALS-FTD, including in presymptomatic C9orf72 mutation carriers, and accumulates at levels highly correlated with those in CSF. Our findings indicate that loss of TDP-43 cryptic splicing repression occurs early in disease progression, even presymptomatically, and that detection of the HDGFL2 cryptic neoepitope serves as a potential diagnostic biomarker for ALS, which should facilitate patient recruitment and measurement of target engagement in clinical trials.

Correlation of vitamin D receptor genotypes, specific IgE levels and other variables with asthma control in children.

INTRODUCTION: Asthma is a common condition affecting millions of children globally. The main goal of this study is to assess factors related to asthma management, particularly atopy level and the impact of genetic variants of the vitamin D receptor (VDR) gene. METHODS: Asthmatic children were enrolled in an outpatient respiratory clinic. Information on patients' medication adherence, medical and medication factors, and sociodemographic were gathered. Spirometry FEV1% and FVC% measurements, and the asthma control test were used to evaluate the severity of asthma, and genotyping of the VDR gene and radioallergosorbent test (RAST) were conducted. Regression analyses were conducted to evaluate variables associated with asthma control and spirometry measures. RESULTS: A total of 313 participants (67.4% males) were recruited in the current study. The mean age was 9.37 (±3.45) years. The mean score for adherence was 4.26 (±2.52), and only 46% of the participants had controlled asthma. Forward conditional stepwise binary regression showed that low and moderate Inhaled corticosteroids (ICS) dose (OR= 0.42 (95% CI 0.20-0.90), p = 0.026; OR = 0.371 (95% CI 0.2-0.72), p = 0.003, respectively) decreased the odds of being in the controlled asthma group, while higher inhaler score (OR = 2.75 (95% CI 2.17-3.49, p < 0.001)) increased the odds of being in the controlled asthma group. However, results found no association between VDR genotype and asthma control, spirometry values or hospitalization due to asthma. CONCLUSIONS: The results indicated that many of the asthma patients had poorly controlled asthma. Factors that were associated with poor asthma control included poor inhaler technique.

Multivalent GU-rich oligonucleotides sequester TDP-43 in the nucleus by inducing high molecular weight RNP complexes.

TDP-43 nuclear clearance and cytoplasmic aggregation are hallmarks of TDP-43 proteinopathies. We recently demonstrated that binding to endogenous nuclear GU-rich RNAs sequesters TDP-43 in the nucleus by restricting its passive nuclear export. Here, we tested the feasibility of synthetic RNA oligonucleotide-mediated augmentation of TDP-43 nuclear localization. Using biochemical assays, we compared the ability of GU-rich oligonucleotides to engage in multivalent, RRM-dependent binding with TDP-43. When transfected into cells, (GU)16 attenuated TDP-43 mislocalization induced by transcriptional blockade or RanGAP1 ablation. Clip34nt and (GU)16 accelerated TDP-43 nuclear re-import after cytoplasmic mislocalization. RNA pulldowns confirmed that multivalent GU-oligonucleotides induced high molecular weight RNP complexes, incorporating TDP-43 and possibly other GU-binding proteins. Transfected GU-repeat oligos disrupted TDP-43 cryptic exon repression, likely by diverting TDP-43 from endogenous RNAs, except for Clip34nt which contains interspersed A and C. Thus, exogenous multivalent GU-RNAs can promote TDP-43 nuclear localization, though pure GU-repeat motifs impair TDP-43 function.

Validation of an Arabic version of the female version of The Sexual Dysfunctional Beliefs Questionnaire: a factor analysis study.

Several questionnaires have been developed to evaluate female sexual dysfunction (FSD) and sexual health problems. However, there is a lack of validated versions of these questionnaires in Arabic. One of the most used instruments is the female version of The Sexual Dysfunctional Beliefs Questionnaire (SDBQ). The current study aimed to validate an Arabic version of the SDBQ. The Arabic version of SDBQ-Female was incorporated into an online questionnaire using and distributed among Jordanian Facebook groups and women-only groups. Factor analysis was performed to investigate evidence for the validity of the questionnaire. 530 females (mean age 30 years, SD = 9) completed the questionnaire. Principal component analysis produced the final model composed of 24 items distributed across four factors: Sexual Desire & Pleasure, Affection Primacy, Sexual Conservatism and Age-Related Beliefs. Confirmatory factor analysis was conducted, and fit indices were acceptable (CMIN/DF = 2.52, GFI = 0.91, AGFI = 0.89, CFI = 0.90, SRMR = 0.05 and RMSEA = 0.05). Income level and marital status both influenced FSD beliefs, with higher scores associated with higher income and being single. The Arabic version of the SDBQ-female demonstrated evidence of validity and reliability. Additional research is necessary to explore beliefs related to FSD within an Arabic context.

This study provides evidence for the validity and reliability of an Arabic questionnaire for assessing female sexual dysfunction (FSD) among Jordanian women recruited through Facebook. Women's income level and marital status influenced their FSD beliefs. Further research is needed to explore these beliefs in an Arabic context.

Loss of TDP-43 splicing repression occurs early in the aging population and is associated with Alzheimer's disease neuropathologic changes and cognitive decline.

LATE-NC, the neuropathologic changes of limbic-predominant age-related TAR DNA-binding protein 43 kDa (TDP-43) encephalopathy are frequently associated with Alzheimer's disease (AD) and cognitive impairment in older adults. The association of TDP-43 proteinopathy with AD neuropathologic changes (ADNC) and its impact on specific cognitive domains are not fully understood and whether loss of TDP-43 function occurs early in the aging brain remains unknown. Here, using a large set of autopsies from the Baltimore Longitudinal Study of Aging (BLSA) and another younger cohort, we were able to study brains from subjects 21-109 years of age. Examination of these brains show that loss of TDP-43 splicing repression, as judged by TDP-43 nuclear clearance and expression of a cryptic exon in HDGFL2, first occurs during the 6th decade, preceding by a decade the appearance of TDP-43+ neuronal cytoplasmic inclusions (NCIs). We corroborated this observation using a monoclonal antibody to demonstrate a cryptic exon-encoded neoepitope within HDGFL2 in neurons exhibiting nuclear clearance of TDP-43. TDP-43 nuclear clearance is associated with increased burden of tau pathology. Age at death, female sex, high CERAD neuritic plaque score, and high Braak neurofibrillary stage significantly increase the odds of LATE-NC. Faster rates of cognitive decline on verbal memory (California Verbal Learning Test immediate recall), visuospatial ability (Card Rotations Test), mental status (MMSE) and semantic fluency (Category Fluency Test) were associated with LATE-NC. Notably, the effects of LATE-NC on verbal memory and visuospatial ability are independent of ADNC. However, the effects of TDP-43 nuclear clearance in absence of NCI on the longitudinal trajectories and levels of cognitive measures are not significant. These results establish that loss of TDP-43 splicing repression is an early event occurring in the aging population during the development of TDP-43 proteinopathy and is associated with increased tau pathology. Furthermore, LATE-NC correlates with high levels of ADNC but also has an impact on specific memory and visuospatial functions in aging that is independent of AD.

Using artificial intelligence to improve public health: a narrative review.

Artificial intelligence (AI) is a rapidly evolving tool revolutionizing many aspects of healthcare. AI has been predominantly employed in medicine and healthcare administration. However, in public health, the widespread employment of AI only began recently, with the advent of COVID-19. This review examines the advances of AI in public health and the potential challenges that lie ahead. Some of the ways AI has aided public health delivery are via spatial modeling, risk prediction, misinformation control, public health surveillance, disease forecasting, pandemic/epidemic modeling, and health diagnosis. However, the implementation of AI in public health is not universal due to factors including limited infrastructure, lack of technical understanding, data paucity, and ethical/privacy issues.

Using a participatory approach to encourage uptake of breast, colorectal, and cervical cancer screening for Scottish Muslim women: a pilot qualitative study.

BACKGROUND: Muslim women use cancer screening less often than the general female population, which puts them at risk of delayed detection. We used an asset-based approach to co-design a faith-based intervention to increase uptake of breast, colorectal, and cervical screening in Scottish Muslim women. METHODS: In this pilot qualitative study, we recruited Muslim women (n=28) of Asian and Arab ethnicity, aged 25-74 years, through snowball sampling from community organisations in Glasgow and Edinburgh. Ten of these women participated in four online workshops in February, 2021, with the aim to codesign the intervention, underpinned by the socio-ecological model and the behaviour change wheel. The final intervention included health education delivered by doctors, testimonials by Muslim women sharing experiences of cancer or screening, and the perspective on cancer screening from a female religious scholar. The intervention was delivered to two groups of eight and ten Muslim women respectively, in March 2021. A week later, the 18 women participated in two focus groups to qualitatively evaluate the intervention. Analyses were conducted thematically. FINDINGS: Themes included barriers to screening, acceptability of content and delivery, attitudinal change, and intervention improvement. Participants believed that lack of awareness was an important barrier to screening. They found the intervention informative. They particularly liked the combination of multiple components, including spirituality, culture, and health education. They valued the faith-based element and highlighted how Islam could facilitate overcoming cultural barriers including social stigma, embarrassment, and modesty, although this could vary with different levels of religiosity. Participants also emphasised that faith-based approaches in isolation would not be enough. They appreciated input of trusted sources such as doctors and religious scholars and were especially drawn to personal narratives. Participants expressed preference for face-to-face delivery and advised using translators to overcome language barriers. INTERPRETATION: Barriers to screening are complex. Using faith as an asset, integrated with the socio-ecological model and behaviour change wheel, resulted in a holistic intervention tackling multiple barriers, which appealed to participants. Collaborating with communities and faith leaders can help to develop culturally sensitive interventions that harness positive aspects of faith for better health outcomes. Intervention effectiveness needs more robust investigation, which we are undertaking in a feasibility study with 200 Muslim women in northeast England and Scotland. FUNDING: Scottish Inequalities Fund, the Scottish Government.

The future of clinical trials-is it virtual?

INTRODUCTION: Participant recruitment to clinical trials is often sub-optimal. Decentralized clinical trials have the potential to address challenges in traditional site-based clinical trial recruitment. SOURCES OF DATA: This review is based on recently published literature and the experience of running a large industry-sponsored interventional trial using both traditional and decentralized methods. AREAS OF AGREEMENT: Efficient delivery of clinical trials is essential to continue to provide therapeutic improvements in a timely and cost-efficient way. Clinical trial designs are constantly evolving to achieve effective trial delivery, manage the complexity of new therapeutic algorithms and conform to cultural developments. AREAS OF CONTROVERSY: Digitally innovative decentralized clinical trials may be a solution to improve recruitment and retention. Although many trials incorporate digital innovations to reduce patient burden, decentralized clinical trials allow remote access to clinical research, potentially enhancing geographical diversity as well as reducing participant burden. GROWING POINTS: Areas for development currently being discussed are developing a 'recruitment platform' that exploits the reach of digital connectivity, automated identification of eligible participants from volunteers, employing technology for remote interaction and exploring the logistic process of delivering the interventions. AREAS TIMELY FOR RELEVANT RESEARCH: The focus of development must ensure that the overall impact will widen participation and reduce inequalities in healthcare.

You clapped, you cheered, but did anybody hear? A mixed-methods systematic review of dementia homecare workers' training and psychosocial needs.

The homecare sector's high turnover rate is linked to poor working conditions and a lack of person-centered practice. Limited research exists on the training and psychosocial needs of homecare workers caring for people living with dementia (PLWD). This systematic review explored these needs and identified 285 studies, of which seven studies met the inclusion criteria. A narrative synthesis identified four themes: "training and education challenges and facilitators;" "social isolation and the importance of peer support;" "emotional attachments and distress experienced by homecare workers;" and "working with families and its emotional impact on homecare workers." This review highlights the unmet educational and psychosocial needs of homecare workers and the negative impacts these unmet needs have. To improve person-centered practice in homecare, workers require dementia-specific training, and concurrent emotional and peer support, alongside support managing relationships with clients' families. Future research is required to implement an intervention to meet these needs.

COVID-19 Vaccination Booster Dose: Knowledge, Practices, and Intention among Pregnant/Planning to Get Pregnant and Lactating Women.

Pregnant women are at higher risk of developing severe COVID-19 symptoms. Therefore, booster dose against COVID-19 was recommended for this special population in Jordan. However, vaccine hesitancy/refusal remains the main obstacle to providing immunity against the spread of COVID-19. Thus, the aim of this study is to examine the intention of pregnant/planning to get pregnant and lactating women towards receiving a booster dose against COVID-19 and its associated factors. A questionnaire was given to Jordanian pregnant/planning to get pregnant and lactating females. A total of 695 females were enrolled in the study. Older age, having a chronic disease, high education, high income, and high perceived risk of COVID-19 were significantly associated with higher knowledge about COVID-19. High perceived risk of COVID-19 was significantly associated with better practice. Participants who anticipated they might contract COVID-19 in the next six months, had high perceived risk of COVID-19, had high knowledge, had received the COVID-19 vaccine based on conviction, and smokers had higher intention to receive a booster dose of the COVID-19 vaccination. In order to increase pregnant and lactating women's intention to receive a booster dose of the COVID-19 vaccine, public health organizations should consider developing comprehensive health education campaigns.

Prevalence and predictors of bullying among in-school adolescents in Nigeria.

Objective: As an emerging significant public health issue affecting many students globally, school bullying is a threat that should not be disregarded. While several published studies have focused on bullying in developed countries, very little is known about the prevalence and predictors of bullying in Nigeria. This study aimed to determine the prevalence and predictors of bullying in secondary schools in Edo State, Nigeria. Method: A descriptive cross-sectional study was conducted with 621 in-school adolescents using a multistage random sampling technique. The 40-item Olweus Bully/Victim Questionnaire (OBVQ) was utilized for data collection. The chi-squared test, Fisher's test, and binomial logistic regression analysis were utilized to examine associations between variables at 5% level of significance. Results: Approximately half of the respondents (51.9%) had experienced at least one type of bullying, while 173 (27.9%) reported themselves as bullies. The most common type of bullying was physical bullying in different forms (belonging taken/stolen-68.3%; kicked, pushed or locked indoor-52.2%; threatened-47.8%), while the most common location of bullying was the classroom in the absence of a teacher (75%); the perpetrators were reported by the majority (58.3%) to be classmates. Respondents in junior classes were 1.61-fold more likely to be bullied than those in senior classes (adjusted odds ratio [AOR]: 1.60; confidence interval [CI]: 1.15-2.24), those who live in rural areas were 1.75-fold more likely to be bullied than urban cities (AOR: 0.45; CI: 0.58-1.80), and those who were frequently beaten by their parents were 2.28-fold more likely to be bullies than those who were not beaten (AOR: 2.16; CI: 1.33-3.52). Furthermore, the act of bullying others was significantly associated with family monthly income (p = 0.01). Conclusion: Owing to the prevalence and predictors of bullying reported in this study, we recommend that policies should be implemented in schools to protect the most affected and vulnerable groups from being victims of school bullying.

'The Addiction Was Making Things Harder for My Mental Health': A Qualitative Exploration of the Views of Adults and Adolescents Accessing a Substance Misuse Treatment Service.

The relationship between substance use and mental health is complex, and both constitute a global public health burden. In the UK, the estimated annual financial costs of alcohol-related harm and illicit drug use are GBP 21.5 billion and GBP 10.7 billion, respectively. This issue is magnified in the North East of England, where treatment access is low and a large proportion of individuals experience socioeconomic deprivation. The present study aimed to explore the experiences of adults and adolescents accessing a substance misuse treatment service in the North East, in order to inform policy makers, commissioners, and providers of substance misuse treatment and prevention. Semi-structured qualitative interviews were conducted with an opportunistic sample of n = 15 adult participants (aged 18 years and over) and n = 10 adolescent participants (aged between 13 and 17 years). Interviews were audio-recorded, transcribed, anonymised, and analysed thematically. Five key themes were identified: (1) initiation of substance use, (2) early life experiences, (3) the bi-directional relationship of mental health and substance use, (4) cessation of substance use, and (5) accessing treatment. Future preventative interventions should focus on providing support to individuals who have been exposed to adverse childhood experiences, with treatment provision for individuals experiencing co-occurring mental health and substance use issues taking a more holistic approach.

A qualitative study exploring attitudes and perceptions of the COVID-19 booster vaccine in minority ethnic individuals in North East England.

Objectives: COVID-19 booster vaccine uptake among minority ethnic individuals in the United Kingdom has been lower than in the general population. This is the case not only for the first and second dose of the vaccine, but particularly for the booster dose. However, little research has examined psychosocial factors contributing to vaccine hesitancy in minority ethnic individuals. This study conducted a qualitative exploration, informed by Protection Motivation Theory, of attitudes towards and perceptions of the COVID-19 booster vaccination among ethnic minority individuals in North East England. Design: Semi-structured interviews were conducted with 16 ethnic minority individuals (11 females, five males) aged between 27 and 57, residing in North East England. Results: Inductive thematic analysis showed that perceived susceptibility to COVID-19 influenced vaccination decisions. Perceived response costs acted as barriers to COVID-19 booster vaccination among interviewees, in the form of time constraints and a perceived lack of practical support in the event of experiencing side effects from the vaccine. There was a lack of confidence in the vaccine, with individuals seeing it as lacking sufficient research. Participants also spoke of medical mistrust due to historical events involving medical experimentation on minority ethnic individuals. Interviewees suggested involving community leaders in addressing people's concerns, misassumptions, and lack of confidence in COVID-19 vaccination. Conclusion: Campaigns to increase COVID-19 booster vaccine uptake need to be designed to address physical barriers towards vaccination, misconceptions, and a lack of confidence in the vaccine. Further research needs to determine the effectiveness of enlisting community leaders in these efforts.

Knowledge, Attitudes, and Practices of Influenza Vaccination among Parents of Children with Asthma: A Cross-Sectional Study.

Asthma is the most common chronic disease in childhood. Exacerbation is a significant problem for asthmatic patients, and viral infections remain the most frequent triggers of asthma exacerbations. This study explored knowledge, attitudes, and practices (KAP) of parents of asthmatic children towards providing influenza vaccine to their children. This cross-sectional study enrolled parents of asthmatic children who visited the outpatient respiratory clinics of two Jordanian hospitals. The present study enrolled 667 parents of asthmatic children (62.8% female). The median age of the participants' children was 7 years. The results showed that 60.4% of the children with asthma never received a flu vaccine. Most of those who had received the flu vaccine reported that the side effects were mild (62.7%). Asthma duration was positively and significantly associated with increased vaccine hesitancy/rejection (OR = 1.093, 95% CI = (1.004-1.190), p = 0.04; and OR = 1.092, 95% CI = (1.002-1.189), p = 0.044, respectively). As the attitude towards flu vaccine score increases, odds of vaccination hesitancy/rejection decreased (OR = 0.735, 95% CI = (0.676-0.800), p < 0.001; and OR = 0.571, 95% CI = (0.514-0.634), p < 0.001, respectively). The main reasons for vaccination hesitancy/refusal included "I don't think my child needs it" (22.3%) followed by "I forget it" (19.5%). The rate of vaccination among children was low and emphasized the necessity of encouraging parents with asthmatic children to vaccinate their children by conducting health awareness campaigns and also emphasized the role of doctors and other healthcare professionals.

Multifaceted Quality Improvement Interventions to Prevent Hemodialysis Catheter-Related Bloodstream Infections: A Systematic Review.

RATIONALE & OBJECTIVE: Central venous catheters (CVCs) are widely used for hemodialysis but are prone to burdensome and costly bloodstream infections. We determined whether multifaceted quality improvement interventions in hemodialysis units can prevent hemodialysis catheter-related bloodstream infections (HDCRBSI). STUDY DESIGN: Systematic review. SETTING & STUDY POPULATIONS: PubMed, EMBASE, and CENTRAL were searched from inception to April 23, 2022, to identify randomized trials, time-series analyses, and before-after studies that examined the effect of multifaceted quality improvement interventions on the incidence of HDCRBSI or access-related bloodstream infections (ARBSI) among people receiving hemodialysis outside of the intensive care unit (ICU). DATA EXTRACTION: Two people independently extracted data and assessed the risk of bias and quality of evidence using validated tools. ANALYTICAL APPROACH: Intervention effects, validity, and characteristics of studies with the same design were compared. Differences between study designs were described. RESULTS: We included 21 studies from 8,824 identified by our search. Among 15 studies that measured HDCRBSI, 2 methodologically heterogenous cluster randomized trials reported discordant intervention effects, 2 interrupted time-series analyses reported favorable interventions with discordant patterns of effect, and 11 before-after studies reported favorable interventions with a very high risk of bias. Among 6 studies that only measured ARBSI, 1 time-series analysis and 1 before-after study did not find a favorable intervention effect, and 4 before-after studies reported a favorable effect with a very high risk of bias. The overall quality of evidence was low for HDCRBSI and very low for ARBSI. LIMITATIONS: Nine definitions of HDCRBSI were used. Ten studies included hospital-based and satellite facilities but did not report separate intervention effects for each type of facility. CONCLUSIONS: Multifaceted quality improvement interventions may prevent HDCRBSI outside the ICU. However, evidence supporting them is of low quality, and further carefully conducted studies are warranted. REGISTRATION: Registered at PROSPERO with registration number CRD42021252290. PLAIN-LANGUAGE SUMMARY: People with kidney failure rely on central venous catheters to facilitate life-sustaining hemodialysis treatments. Unfortunately, hemodialysis catheters are a common source of problematic bloodstream infections. Quality improvement programs have effectively prevented catheter-related infections in intensive care units, but it is unclear whether they can be adapted to patients using hemodialysis catheters in the community. In a systematic review that included 21 studies, we found that most quality improvement programs were reported to be successful. However, the findings were mixed among higher-quality studies, and overall the quality of evidence was low. Ongoing quality improvement programs should be complemented by more high-quality research.