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Nutritional analysis and characterization of carbapenemase producing-<i>Klebsiella pneumoniae</i> resistant genes associated with bovine mastitis infected cow’s milk

by Mr. Saddam, Muddasir Khan, Muhsin Jamal, Sadeeq Ur Rahman, Abdul Qadeer, Imad Khan, Mohamed H. Mahmoud, Gaber El-Saber Batiha, Syed Hussain Shah

The current study was designed to analyze nutritional parameters and to characterize carbapenemase producing-Klebsiella pneumoniae isolates from bovine mastitic cow’s milk. Out of 700 milk samples K. pneumoniae was identified by phenotypic and molecular techniques along with their antibiogram analysis and nutritional analysis was performed using the procedure of Association of Official Analytical Chemists. Carbapenemase-producing K. pneumoniae was detected by phenotypic CarbaNP test followed by molecular characterization of their associated resistant genes blaVIM, blaKPC, blaOXA-48, blaNDM, and blaIMP along with insertion sequence common region 1 (ISCR1) and integrons (Int1, Int2, and Int3) genes. Among nutritional parameters, fat content was observed (2.99%) followed by protein (2.78%), lactose (4.32%), and total solid (11.34%), respectively. The prevalence of K. pneumoniae among bovine mastitis was found 25.71%. Antibiogram analysis revealed that more effective antibiotics was ceftazidime (80%) followed by amikacin (72%), while highly resistant antibiotics was Fusidic acid (100%). Distribution of carbapenemase producer K. pneumoniae was found 44.4%. Among carbapenem resistant genes blaKPC was found 11.25%, blaVIM 2.75%, blaNDM 17.5%, and blaOXA-48 7.5%, while blaIMP gene was not detected. Furthermore, distribution of ISCR1 was found 40%, while integron 1 was found 61.2% followed by integron 2 (20%), and integron 3 (5%). In conclusion, the recent scenario of carbapenemase resistant K. pneumoniae isolates responsible for mastitis may affect not only the current treatment regime but also possess a serious threat to public health due to its food borne transmission and zoonotic potential.

Quantifying the potential epidemiological impact of a 2-year active case finding for tuberculosis in rural Nepal: a model-based analysis

Por: Shrestha · S. · Mishra · G. · Hamal · M. · Dhital · R. · Shrestha · S. · Shrestha · A. · Shah · N. P. · Khanal · M. · Gurung · S. · Caws · M.
Objectives

Active case finding (ACF) is an important tuberculosis (TB) intervention in high-burden settings. However, empirical evidence garnered from field data has been equivocal about the long-term community-level impact, and more data at a finer geographic scale and data-informed methods to quantify their impact are necessary.

Methods

Using village development committee (VDC)-level data on TB notification and demography between 2016 and 2017 in four southern districts of Nepal, where ACF activities were implemented as a part of the IMPACT-TB study between 2017 and 2019, we developed VDC-level transmission models of TB and ACF. Using these models and ACF yield data collected in the study, we estimated the potential epidemiological impact of IMPACT-TB ACF and compared its efficiency across VDCs in each district.

Results

Cases were found in the majority of VDCs during IMPACT-TB ACF, but the number of cases detected within VDCs correlated weakly with historic case notification rates. We projected that this ACF intervention would reduce the TB incidence rate by 14% (12–16) in Chitwan, 8.6% (7.3–9.7) in Dhanusha, 8.3% (7.3–9.2) in Mahottari and 3% (2.5–3.2) in Makwanpur. Over the next 10 years, we projected that this intervention would avert 987 (746–1282), 422 (304–571), 598 (450–782) and 197 (172–240) cases in Chitwan, Dhanusha, Mahottari and Makwanpur, respectively. There was substantial variation in the efficiency of ACF across VDCs: there was up to twofold difference in the number of cases averted in the 10 years per case detected.

Conclusion

ACF data confirm that TB is widely prevalent, including in VDCs with relatively low reporting rates. Although ACF is a highly efficient component of TB control, its impact can vary substantially at local levels and must be combined with other interventions to alter TB epidemiology significantly.

Understanding the dynamics of chemsex among men who have sex with men, male sex workers and transgender women in Dhaka, Bangladesh: a multiphase sequential mixed-method research protocol

Por: Sarwar · G. · Irfan · S. D. · Reza · M. · Khan · M. N. M. · Khan · S. I.
Introduction

Chemsex is defined as drug use to enhance sexual pleasure. Global literature illustrated the pervasiveness of chemsex among men who have sex with men (MSM) and transgender women (hijra) for prolonging anal intercourse, reducing pain and intensifying pleasure, oftentimes without condoms. Global literature highlighted the association between chemsex and unsafe sexual behaviours. These circumstances warrant targeted chemsex research to explore the chemsex situation. The study aims to explore the overall dynamics of chemsex among MSM, male sex workers (MSW) and hijra in Dhaka, Bangladesh and formulate culturally relevant, context-specific, gender-sensitive and evidence-based recommendations for chemsex interventions.

Methods and analysis

This will be a sequential, exploratory, mixed-methods study. Data will be collected at four drop-in centres in Dhaka in three phases. To explore issues related to chemsex, the formative phase (phase 1) will generate evidence on the overall dynamics of chemsex through a literature review and qualitative interviews. Qualitative data will be manually analysed using thematic analysis. In phase 2, a cross-sectional survey will be conducted among 458 MSM, male sex workers and hijra to measure the prevalence, reasons and sexual risk behaviour associated with chemsex. In phase 3, qualitative interviews will be conducted with the participants involved in chemsex, service providers and relevant stakeholders to add qualitative depth to survey responses. In this phase, service provision will also be investigated for people engaging in chemsex. Moreover, based on the findings of phases 1 and 2, and qualitative interviews of phase 3, a preliminary chemsex intervention model will be developed through a series of intervention design workshops.

Ethics and dissemination

Ethical approval has been attained from the Ethical Review Committee of icddr,b. Informed consent will be obtained from the participants, and confidentiality will be maintained during data collection and storage. Findings will be disseminated via several platforms including dissemination seminars, scientific articles and study report.

Comparing proficiency of obstetrics and gynaecology trainees with general surgery trainees using simulated laparoscopic tasks in Health Education England, North-West: a prospective observational study

Por: Khan · Z. N. · Shrestha · D. · Shugaba · A. · Lambert · J. E. · Clark · J. · Haslett · E. · Afors · K. · Bampouras · T. M. · Gaffney · C. J. · Subar · D. A.
Background

Training programmes for obstetrics and gynaecology (O&G) and general surgery (GS) vary significantly, but both require proficiency in laparoscopic skills. We sought to determine performance in each specialty.

Design

Prospective, observational study.

Setting

Health Education England North-West, UK.

Participants

47 surgical trainees (24 O&G and 23 GS) were subdivided into four groups: 11 junior O&G, 13 senior O&G, 11 junior GS and 12 senior GS trainees.

Objectives

Trainees were tested on four simulated laparoscopic tasks: laparoscopic camera navigation (LCN), hand–eye coordination (HEC), bimanual coordination (BMC) and suturing with intracorporeal knot tying (suturing).

Results

O&G trainees completed LCN (p

Discussion

GS trainees performed better than O&G trainees in core laparoscopic skills, and the structure of O&G training may require modification.

Trial registration number

ClinicalTrials.gov Registry (NCT05116332).

'They say: medical students perceptions of General Practice, experiences informing these perceptions, and their impact on career intention--a qualitative study among medical students in England

Por: Banner · K. · Alberti · H. · Khan · S. A. · Jones · M. M. · Pope · L. M.
Objectives

The number of UK graduates choosing General Practice training remains significantly lower than the current numbers required to meet the demands of the service. This work aims to explore medical students’ perceptions of General Practice, experiences which lead to the development of these perceptions, and the ultimate impact of these on career intention.

Design

This mixed-methods, qualitative study used focus groups, semistructured interviews, longitudinal audio diary data and debrief interviews to explore and capture the experiences and perceptions of students in their first and penultimate years of university.

Setting

Three English medical schools.

Participants

Twenty students were recruited to focus groups from first and fourth/fifth year of study. All students in these years of study were invited to attend. Six students were recruited into the longitudinal diary study to further explore their experiences.

Results

This work identified that external factors, internal driving force and the ‘they say’ phenomenon were all influential on the development of perceptions and ultimately career intention. External factors may be split into human or non-human influences, for example, aspirational/inspirational seniors, family, peers (human), placements and ‘the push’ of GP promotion (non-human). Driving force refers to internal factors, to which the student compares their experiences in an ongoing process of reflection, to understand if they feel General Practice is a career they wish to pursue. The ‘they say’ phenomenon refers to a passive and pervasive perception, without a known source, whereby usually negative perceptions circulate around the undergraduate community.

Conclusion

Future strategies to recruit graduates to General Practice need to consider factors at an undergraduate level. Positive placement experiences should be maximised, while avoiding overtly ‘pushing’ GP onto students.

In silico exploration of <i>Serratia</i> sp. BRL41 genome for detecting prodigiosin Biosynthetic Gene Cluster (BGC) and in vitro antimicrobial activity assessment of secreted prodigiosin

by Farhana Boby, Md. Nurul Huda Bhuiyan, Barun Kanti Saha, Subarna Sandhani Dey, Anik Kumar Saha, Md Jahidul Islam, Mahci Al Bashera, Shyama Prosad Moulick, Farhana Jahan, Md. Asad Uz Zaman, Sanjana Fatema Chowdhury, Showti Raheel Naser, Md. Salim Khan, Md. Murshed Hasan Sarkar

The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. “Prodigiosin NRPS”, among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 μg/mL and 7.81 to 31.25 μg/mL respectively. At concentration 500 μg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 μg/mL pigment where 125 μg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections.

Patterns, prevalence and risk factors of intimate partner violence and its association with mental health status during COVID-19: a cross-sectional study on early married female adolescents in Khulna district, Bangladesh

Por: Nishat · J. F. · Khan · U. S. · Shovo · T.-E.-A. · Ahammed · B. · Rahman · M. M. · Hossain · M. T.
Objectives

This study was designed to identify the patterns, prevalence and risk factors of intimate partner violence (IPV) against female adolescents and its association with mental health problems.

Design

Cross-sectional survey.

Settings

Dumuria Upazila (subdistrict) under the Khulna district of Bangladesh.

Participants

A total of 304 participants were selected purposively based on some specifications: they must be female adolescents, residents of Dumuria Upazila and married during the COVID-19 pandemic when under 18 years of age.

Outcome measures

By administering a semi-structured interview schedule, data were collected regarding IPV using 12 five-point Likert scale items; a higher score from the summation reflects frequent violence.

Results

The findings suggest that the prevalence of physical, sexual and emotional IPV among the 304 participants, who had an average age of 17.1 years (SD=1.42), was 89.5%, 87.8% and 93.7%, respectively, whereas 12.2% of the participants experienced severe physical IPV, 9.9% experienced severe sexual IPV and 10.5% experienced severe emotional IPV. Stepwise regression models identified age at marriage (p=0.001), number of miscarriages (p=0.005), education of spouse (p=0.001), income of spouse (p=0.016), age gap between spouses (p=0.008), marital adjustment (p

Conclusion

During the COVID-19 pandemic, an increase in IPV and mental health problems among early married adolescents was documented. To reduce physical and mental harm and to assure their well-being, preventive and rehabilitative measures should be devised.

A qualitative evaluation of the impact of a medical student school outreach project on both medical students and school pupils

Por: Brown · M. E. L. · Ahuja · N. · Sivam · V. · Khanna · A. · Parekh · R.
Objective

To explore medical student and school pupil experiences of an outreach school teaching project.

Setting

Community engagement is increasingly commonplace within medical school. Secondary schools offer ample opportunities for community engagement as medical students teach and engage in service learning. There is a lack of research regarding the impact of school community engagement projects and the impact on pupils, as critical stakeholders in the service medical students provide. In this qualitative study, we explore the perspectives of medical students and school pupils involved in a school teaching project.

Participants

Ten medical students participated in individual interviews, and 17 school pupils across three schools participated in group interviews. Data were analysed using thematic analysis and the concept of service learning.

Results

For medical students, the project fostered communication and teaching skills, but a lack of reflection hampered further benefit. For school pupils, experiences varied – learning about careers in medicine could be inspiring, but content pitched at the incorrect level disengaged some pupils. The conflict between session timing and medical students’ exams negatively influenced engagement.

Conclusions

To shift the focus of community engagement projects that promote service-learning towards mutual benefit, designing in partnership with relevant community stakeholders and integrating opportunities to reflect on these experiences are critical.

Are pharmacists on the front lines of the opioid epidemic? A cross-sectional study of the practices and competencies of community and hospital pharmacists in Punjab, Pakistan

Por: Mubarak · N. · Zahid · T. · Rana · F. R. · Ijaz · U.-E.-B. · Shabbir · A. · Manzoor · M. · Khan · N. · Arif · M. · Naeem · M. M. · Kanwal · S. · Saif-ur-Rehman · N. · Zin · C. S. · Mahmood · K. · Asgher · J. · Elnaem · M. H.
Introduction

Countries are grappling with a rapidly worsening upsurge in the opioid-related overdose deaths, misuse and abuse. There is a dearth of data in Pakistan regarding the practices and competencies of pharmacists in handling opioid-related issues.

Study design

A cross-sectional study, conducted across Punjab, Pakistan.

Method

The study deployed a validated survey to evaluate the competencies and practices of the community and hospital pharmacists.

Results

504 community pharmacists and 279 hospital pharmacists participated in the survey with an overall response rate of 85.5%. Almost half of the respondents ‘never’ or ‘sometimes’ made clinical notes in a journal or dispensing software to monitor ongoing opioid use. Generally, pharmacists were reluctant to collaborate with physicians or notify police regarding the abuse/misuse of opioids. Hospital pharmacists achieved significantly higher mean competency scores than chain and independent community pharmacists (p

Conclusion

Both community and hospital pharmacists hold significant positions and potential to contribute meaningfully to the mitigation of harms and risks associated with opioids. Nevertheless, this study underscores notable deficiencies in the competence of pharmacists, whether in hospital or community settings in Punjab, concerning various aspects related to the dispensing and utilisation of opioids. It also highlights the pressing need for the development of strategies aimed at improving several practice areas including the documentation, the quality of patient counselling, the effectiveness of reporting mechanisms for opioid abuse and the stringent enforcement of regulatory policies to curtail opioid misuse. Thus, to mitigate the opioid epidemic in Pakistan, it is imperative to institute opioid stewardship initiatives aimed at rectifying the competency and procedural deficiencies within the pharmacist workforce.

BMP9 is a potent inducer of chondrogenesis, volumetric expansion and collagen type II accumulation in bovine auricular cartilage chondroprogenitors

by Oliver F. W. Gardner, Yadan Zhang, Ilyas M. Khan

Reconstruction of the outer ear currently requires harvesting of cartilage from the posterior of the auricle or ribs leading to pain and donor site morbidity. An alternative source for auricular reconstruction is in vitro tissue engineered cartilage using stem/progenitor cells. Several candidate cell-types have been studied with tissue-specific auricular cartilage progenitor cells (AuCPC) of particular interest. Whilst chondrogenic differentiation of competent stem cells using growth factor TGFβ1 produces cartilage this tissue is frequently fibrocartilaginous and lacks the morphological features of hyaline cartilage. Recent work has shown that growth factor BMP9 is a potent chondrogenic and morphogenetic factor for articular cartilage progenitor cells, and we hypothesised that this property extends to cartilage-derived progenitors from other tissues. In this study we show monoclonal populations of AuCPCs from immature and mature bovine cartilage cultured with BMP9 produced cartilage pellets have 3-5-fold greater surface area in sections than those grown with TGFβ1. Increased volumetric growth using BMP9 was due to greater sGAG deposition in immature pellets and significantly greater collagen accumulation in both immature and mature progenitor pellets. Polarised light microscopy and immunohistochemical analyses revealed that the organisation of collagen fibrils within pellets is an important factor in the growth of pellets. Additionally, chondrocytes in BMP9 stimulated cell pellets had larger lacunae and were more evenly dispersed throughout the extracellular matrix. Interestingly, BMP9 tended to normalise the response of immature AuCPC monoclonal cell lines to differentiation cues whereas cells exhibited more variation under TGFβ1. In conclusion, BMP9 appears to be a potent inducer of chondrogenesis and volumetric growth for AuCPCs a property that can be exploited for tissue engineering strategies for reconstructive surgery though with the caveat of negligible elastin production following 21-day treatment with either growth factor.

The burden of non-disabled frailty and its associated factors among older adults in Bangladesh

by Sabuj Kanti Mistry, A. R. M. Mehrab Ali, Uday Narayan Yadav, Saruna Ghimire, Afsana Anwar, Md. Nazmul Huda, Fouzia Khanam, Rashidul Alam Mahumud, Ateeb Ahmad Parray, Shovon Bhattacharjee, David Lim, Mark Fort Harris

Objective

The present study aims to measure the prevalence of non-disabled frailty and its associated factors among Bangladeshi older adults.

Methods

This cross-sectional study was conducted during September and October 2021 among 1,045 Bangladeshi older adults (≥60 years). Telephone interviews, using a semi-structured questionnaire, were undertaken to collect data on participants’ characteristics and level of frailty. The non-disabled frailty was measured using the ‘Frail Non-Disabled (FiND)’ questionnaire. A multinomial logistic regression model assessed the factors associated with frailty among the participants.

Results

Around a quarter of the participants (24.8%) were frail. The multinomial regression analysis showed that older participants aged ≥80 years (RRR = 3.23, 95% CI: 1.41–7.37) were more likely to be frail compared to participants aged 60–69 years. Likewise, the participants living in a large family with ≥4 members (RRR = 1.39, 95% CI: 1.01–1.92) were more likely to be frail compared to those living in smaller families. Also, participants having memory or concentration problems (RRR = 1.56, 95% CI: 1.12–2.17) were more likely to be frail compared to those who were not suffering from these problems. Moreover, participants whose family members were non-responsive to their day-to-day assistance (RRR = 1.47, 95% CI: 1.06–2.03) were more likely to be frail compared to those whose family members were responsive. Furthermore, participants who were feeling lonely (RRR = 1.45, 95% CI: 1.07–1.98) were more likely to be frail than their counterparts who were not feeling lonely.

Conclusions

The findings of the present study suggest developing tailored interventions to address the burden of frailty among the older populations in Bangladesh. In particular, providing long-term care and health promotion activities can be of value in preventing frailty and reducing adverse health outcomes among this vulnerable population group.

Parental supporter in pediatric resuscitation: A mixed‐method study with Delphi and analytic hierarchy process

Abstract

Introduction

Providing support to parents is an evidence-based practice and a crucial part of family-centered nursing care. However, it is not clear who and how to provide the best support to parents during and after their child's resuscitation attempts.

Purpose

This study was conducted to explore the characteristics and roles of parental supporters responsible for caring for parents during and after their child's resuscitation.

Methods

This is a mixed-method study combining the Delphi technique and the Analytic Hierarchy Process. A list of potentially important items describing the characteristics and roles of parental supporters caring for parents during and after pediatric resuscitation was developed through qualitative interviews with parents and members of the resuscitation team, and a thorough literature search. Then, the Delphi round was conducted with key experts. In the final step, the Analytic Hierarchy Process was used for ranking items in the order of their importance.

Results

A list with 69 items describing the characteristics and roles of parental supporters was developed. 15 items (21.74%) were related to the “Characteristics of parental supporter” category; 8 items (11.59%) were related to the “Roles of a parental supporter during resuscitation” category; 13 items (18.84%) were related to the “Roles of a parental supporter after successful resuscitation” category; 23 items (33.34%) were related to the “Roles of a parental supporter after unsuccessful resuscitation” category; and 10 items (14.49%) were related to the “Roles of a parental supporter after unsuccessful resuscitation with help of other staff of the hospital” category.

Conclusion

The findings of this study can be used to develop guidelines that include parental supporter characteristics and roles to support parents during and after their child's resuscitation according to family-centered care practices in pediatric settings.

Clinical Relevance

Study findings indicate the need for the presence of a parental supporter during and after pediatric resuscitation, whether witnessed by the parents or not. Knowledge regarding the characteristics and roles of parental supporters can be used in practice to uphold family-centered nursing care during critical situations.

Investigating the relationship of COVID-19 preventive and mitigation measures with mosque attendance in Pakistan

by Hamza Umer, Muhammad Salar Khan

Social distancing served as a principal strategy to curtail the spread of COVID-19. However, congregational activities in mosques made it challenging to practice social distancing and led to a rapid surge in virus infections in several Muslim countries. This study uses nationally representative cross-sectional data from Pakistan, a Muslim-majority country, to examine the relationship of practicing preventive measures (such as social distancing, wearing mask and hand washing) and mitigation measures (like avoid going to the market, social gatherings, healthcare seeking, use of public transport, and long-distance travel) with mosque visits by utilizing logistic regressions. The results show that individuals adhering to preventive and mitigation measures also avoid visiting mosques and other religious gatherings. From a policy perspective, these results suggest that the government of Pakistan can avoid direct religious confrontation when it needs to minimize mosque visits to curtail the spread of the virus by implementing preventive and mitigation measures.

Comparison of the preconditioning effect of different exercise training modalities on myocardial ischemia-reperfusion injury

by Reihaneh Mohammadkhani, Kamal Ranjbar, Iraj Salehi, Alireza Komaki, Ebrahim Zarrinkalam, Parsa Amiri

The study of exercise preconditioning can develop strategies to prevent cardiovascular diseases and outline the efficient exercise model. However, the exercise type with the most protective effect against ischemia-reperfusion injury is unknown. In this study, we examined the effects of three kinds of exercise preconditioning on myocardial ischemia-reperfusion in adult rats and explored the possible underlying mechanisms. Male Wistar rats subjected to ten weeks of endurance, resistance, and concurrent training underwent ischemia (30 min) and reperfusion (120 min) induction. Then, infarction size, serum levels of the CK-MB, the redox status, and angiogenesis proteins (VEGF, ANGP-1, and ANGP-2) were measured in the cardiac tissue. Results showed that different exercise training modes have the same reduction effects on infarction size, but ischemia-reperfusion-induced CK-MB was lower in response to endurance training and concurrent training. Furthermore, cardiac VEGF levels increased in all three kinds of exercise preconditioning but ischemia-reperfusion-induced ANGP-1 elevated more in endurance training. The cardiac GPX activity was improved significantly through the resistance and concurrent exercise compared to the endurance exercise. In addition, all three exercise preconditioning models decreased MPO levels, and ischemia reperfusion-induced MDA was lower in endurance and resistance training. Overall, these results indicated that cardioprotection of exercise training against ischemia-reperfusion injury depends on the exercise modality. Cardioprotective effects of aerobic, resistance, and concurrent exercises are due to different mechanisms. The preconditioning effects of endurance training are mediated mainly by pervasive angiogenic responses and resistance training through oxidative stress amelioration. The preconditioning effects of concurrent training rely on both angiogenesis and oxidative stress amelioration.

Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis

by Tasnim F. Imran, Ali A. Khan, Phinnara Has, Alexis Jacobson, Stephanie Bogin, Mahnoor Khalid, Asim Khan, Samuel Kim, Sebhat Erqou, Gaurav Choudhary, Karen Aspry, Wen-Chih Wu

Background

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.

Objective

The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.

Methods

Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.

Results

In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12–52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p Conclusion

PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.

Estimating the frequency of inpatient adverse events using a two-step retrospective chart review: a study protocol

Por: ul Hassan · S. S. · Asif · F. · Haque · G. · Ayub · F. · Munir · T. · Khan · F. · Siddiqi · S. · Latif · A.
Introduction

Adverse events are a major cause of patient harm in the hospitalised setting. Low-income and middle-income countries account for a disproportionate share of the global burden of adverse events. However, patient safety research is still centred around high-income countries and high-resource health systems. The methods and data produced from these efforts are ill-suited to low-income and middle-income systems due to the social and technical differences between these settings. We aim to use our pilot-tested, locally developed methodology to estimate the frequency and characteristics of adverse events in hospitalised patients in a lower-middle-income country to inform patient safety policies and initiatives.

Methods and analysis

This multi-centre study will employ a two-step chart review methodology to identify adverse events in a representative sample of patients admitted at five hospitals between 1 January 2019 and 31 December 2019. The first step will include assessing patient files against a list of triggers to detect adverse events and the second step will involve an in-depth review of the events to capture pertinent characteristics. The triggers have been adapted from validated tools used in other studies. The reviewing team will be trained on the use of research tools and operational definitions to ensure that data are collected uniformly. The main outcome of interest is the rate at which adverse events occur in hospitalised patients. Further analysis will look to identify and quantify associations between the main outcome of interest and a variety of variables such as patient age and gender using tests of independence and regression techniques.

Ethics and dissemination

This study protocol has been approved by the Ethics Review Committee at Aga Khan University (Reference number: 2023-6324-24566). The findings of this study will be published in a peer-reviewed journal and disseminated to the public through national and international conferences, workshops, websites and social media.

Characteristics of patients attached to near-retirement family physicians: a population-based serial cross-sectional study in Ontario, Canada

Por: Premji · K. · Green · M. E. · Glazier · R. H. · Khan · S. · Schultz · S. E. · Mathews · M. · Nastos · S. · Frymire · E. · Ryan · B. L.
Objectives

Population ageing is a global phenomenon. Resultant healthcare workforce shortages are anticipated. To ensure access to comprehensive primary care, which correlates with improved health outcomes, equity and costs, data to inform workforce planning are urgently needed. We examined the medical and social characteristics of patients attached to near-retirement comprehensive primary care physicians over time and explored the early-career and mid-career workforce’s capacity to absorb these patients.

Design

A serial cross-sectional population-based analysis using health administrative data.

Setting

Ontario, Canada, where most comprehensive primary care is delivered by family physicians (FPs) under universal insurance.

Participants

All insured Ontario residents at three time points: 2008 (12 936 360), 2013 (13 447 365) and 2019 (14 388 566) and all Ontario physicians who billed primary care services (2008: 11 566; 2013: 12 693; 2019: 15 054).

Outcome measures

The number, proportion and health and social characteristics of patients attached to near-retirement age comprehensive FPs over time; the number, proportion and characteristics of near-retirement age comprehensive FPs over time. Secondary outcome measures: The characteristics of patients and their early-career and mid-career comprehensive FPs.

Results

Patient attachment to comprehensive FPs increased over time. The overall FP workforce grew, but the proportion practicing comprehensiveness declined (2008: 77.2%, 2019: 70.7%). Over time, an increasing proportion of the comprehensive FP workforce was near retirement age. Correspondingly, an increasing proportion of patients were attached to near-retirement physicians. By 2019, 13.9% of comprehensive FPs were 65 years or older, corresponding to 1 695 126 (14.8%) patients. Mean patient age increased, and all physicians served markedly increasing numbers of medically and socially complex patients.

Conclusions

The primary care sector faces capacity challenges as both patients and physicians age and fewer physicians practice comprehensiveness. Nearly 15% (1.7 million) of Ontarians may lose their comprehensive FP to retirement between 2019 and 2025. To serve a growing, increasingly complex population, innovative solutions are needed.

Temporal trends of hemoglobin among pregnant women: The Mutaba’ah study

by Aminu S. Abdullahi, Abubaker Suliman, Moien AB Khan, Howaida Khair, Saad Ghazal-Aswad, Iffat Elbarazi, Fatima Al-Maskari, Tom Loney, Rami H. Al-Rifai, Luai A. Ahmed

Background

Low hemoglobin (Hb) level is a leading cause of many adverse pregnancy outcomes. Patterns of changes in Hb levels during pregnancy are not well understood.

Aim

This study estimated Hb levels, described its changing patterns across gestational trimesters, and identified factors associated with these changes among pregnant women.

Materials and methods

Data from the ongoing maternal and child health cohort study–The Mutaba’ah Study, was used (N = 1,120). KML machine learning algorithm was applied to identify three distinct cluster trajectories of Hb levels between the first and the third trimesters. Descriptive statistics were used to profile the study participants. Multinomial multivariable logistic regression was employed to identify factors associated with change patterns in Hb levels.

Results

The three identified clusters–A, B and C–had, respectively, median Hb levels (g/L) of 123, 118, and 104 in the first trimester and 119, 100, and 108 in the third trimester. Cluster ’A’ maintained average normal Hb levels in both trimesters. Cluster ’B’, on average, experienced a decrease in Hb levels below the normal range during the third trimester. Cluster ’C’ showed increased Hb levels in the third trimester but remained, on average, below the normal range in both trimesters. Pregnant women with higher gravida, diabetes mellitus (type 1 or 2), nulliparity or lower level of education were more likely to be in cluster ’B’ than the normal cluster ’A’. Pregnant women who reported using iron supplements before pregnancy or those with low levels of education. were more likely to be in cluster ’C’ than the normal cluster ’A’.

Conclusion

The majority of pregnant women experienced low Hb levels during pregnancy. Changes in Hb levels during pregnancy were associated with parity, gravida, use of iron before pregnancy, and the presence of diabetes mellitus (type 1 or 2).

Cohort profile: the Pregnancy Risk Infant Surveillance and Measurement Alliance (PRISMA) - Pakistan

Por: Naz · S. · Jaffar · A. · Yazdani · N. · Kashif · M. · Hussain · Z. · Khan · U. · Farooq · F. · Nisar · M. I. · Jehan · F. · Smith · E. · Hoodbhoy · Z.
Purpose

Pakistan has disproportionately high maternal and neonatal morbidity and mortality. There is a lack of detailed, population-representative data to provide evidence for risk factors, morbidities and mortality among pregnant women and their newborns. The Pregnancy Risk, Infant Surveillance and Measurement Alliance (PRISMA) is a multicountry open cohort that aims to collect high-dimensional, standardised data across five South Asian and African countries for estimating risk and developing innovative strategies to optimise pregnancy outcomes for mothers and their newborns. This study presents the baseline maternal and neonatal characteristics of the Pakistan site occurring prior to the launch of a multisite, harmonised protocol.

Participants

PRISMA Pakistan study is being conducted at two periurban field sites in Karachi, Pakistan. These sites have primary healthcare clinics where pregnant women and their newborns are followed during the antenatal, intrapartum and postnatal periods up to 1 year after delivery. All encounters are captured electronically through a custom-built Android application. A total of 3731 pregnant women with a mean age of 26.6±5.8 years at the time of pregnancy with neonatal outcomes between January 2021 and August 2022 serve as a baseline for the PRISMA Pakistan study.

Findings to date

In this cohort, live births accounted for the majority of pregnancy outcomes (92%, n=3478), followed by miscarriages/abortions (5.5%, n=205) and stillbirths (2.6%, n=98). Twenty-two per cent of women (n=786) delivered at home. One out of every four neonates was low birth weight (

Future plans

The PRISMA cohort will provide data-driven insights to prioritise and design interventions to improve maternal and neonatal outcomes in low-resource regions.

Trial registration number

NCT05904145.

Investigating automated regression models for estimating left ventricular ejection fraction levels in heart failure patients using circadian ECG features

by Sona M. Al Younis, Leontios J. Hadjileontiadis, Aamna M. Al Shehhi, Cesare Stefanini, Mohanad Alkhodari, Stergios Soulaidopoulos, Petros Arsenos, Ioannis Doundoulakis, Konstantinos A. Gatzoulis, Konstantinos Tsioufis, Ahsan H. Khandoker

Heart Failure (HF) significantly impacts approximately 26 million people worldwide, causing disruptions in the normal functioning of their hearts. The estimation of left ventricular ejection fraction (LVEF) plays a crucial role in the diagnosis, risk stratification, treatment selection, and monitoring of heart failure. However, achieving a definitive assessment is challenging, necessitating the use of echocardiography. Electrocardiogram (ECG) is a relatively simple, quick to obtain, provides continuous monitoring of patient’s cardiac rhythm, and cost-effective procedure compared to echocardiography. In this study, we compare several regression models (support vector machine (SVM), extreme gradient boosting (XGBOOST), gaussian process regression (GPR) and decision tree) for the estimation of LVEF for three groups of HF patients at hourly intervals using 24-hour ECG recordings. Data from 303 HF patients with preserved, mid-range, or reduced LVEF were obtained from a multicentre cohort (American and Greek). ECG extracted features were used to train the different regression models in one-hour intervals. To enhance the best possible LVEF level estimations, hyperparameters tuning in nested loop approach was implemented (the outer loop divides the data into training and testing sets, while the inner loop further divides the training set into smaller sets for cross-validation). LVEF levels were best estimated using rational quadratic GPR and fine decision tree regression models with an average root mean square error (RMSE) of 3.83% and 3.42%, and correlation coefficients of 0.92 (p
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