Effect of metformin use on graft and patient survival in kidney transplant recipients with type 2 diabetes: a systematic review protocol.

INTRODUCTION: Metformin is a first-line antihyperglycaemic agent for type 2 diabetes (T2DM). In addition to glycaemic control, it offers benefits related to cardiovascular health, weight neutrality and metabolic syndrome. However, its benefits in kidney transplant recipients remain unclear as metformin use is controversial in this population due to a lack of evidence and there are recommendations against its use in patients with poor kidney function. Hence, we seek to describe a protocol for a systematic review, which will assess the impact of metformin use on graft survival and mortality in kidney transplant recipients. METHODS: This protocol was guided by the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015. We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science Core Collection for relevant studies conducted in kidney transplant recipients using metformin, which report outcomes related to graft and patient survival. All studies meeting these criteria in adults and published in English from inception to 2023 will be included in our review. We will employ the Cochrane Risk of Bias Tool 2 for randomised controlled trials and the Risk of Bias in Non-randomised Studies of Intervention for non-randomised studies. We will present our data and study characteristics in a table format and determine if a meta-analysis can be performed by clinical and methodological heterogeneity, using the I2 statistics. If a meta-analysis cannot be performed, we will provide a narrative synthesis of included studies using the Synthesis Without Meta-Analysis Reporting Guideline. ETHICS AND DISSEMINATION: Ethical approval will not be required for this review as the data used will be extracted from already published studies with publicly accessible data. As this study will assess the impact of metformin use on graft and patient survival in kidney transplant recipients, evidence gathered through it will be disseminated using traditional approaches that include open-access peer-reviewed publication, scientific presentations and a report. We will also disseminate our findings to appropriate academic bodies in charge of publishing guidelines related to T2DM and transplantation, as well as patient and research centred groups. PROSPERO REGISTRATION NUMBER: CRD42023421799.

Factors associated with road traffic injury in a high-risk zone of Bangladesh: a mixed-method study.

INTRODUCTION: Road traffic injuries are a significant public health issue in low-income and middle-income countries. This study was designed to explore the pattern and factors associated with road traffic injury in a high-risk zone of Bangladesh. METHOD: This mixed-method study included a total of 363 road traffic injury victims for the quantitative component, and 10 traffic-related officials and 10 drivers for the qualitative element. Data were collected using a pretested questionnaire, key informant interviews and a focus group discussion using a focus group discussion guide. Quantitative and qualitative analyses were done using Stata V.17 and NVivo V.12, respectively. RESULTS: Most participants were male, illiterate and young (<30 years) with age averaging 31.50±9.16 years. Of all road traffic injury victims, most had mild (45.18%) injuries, and the least had severe (5.79%) injuries, with head being the most common site (34.44%). The highest proportion of injuries were sustained by motor vehicle drivers (57.58%), followed by cyclists/rickshaw pullers (22.59%) and passengers (19.83%). Most vehicles were new (75.21%), and the rest were old (24.79%). Nearly one-third of the participants did not know about driving rules. The presence of knowledge was associated with less severe injury (p=0.031) compared with the absence of knowledge. The qualitative component of the study identified several factors related to road traffic injury, including driver factors (lack of sleep, bad driving habits and lack of helmets), driving activity factors (ignoring rules, overtaking, crossing speed limits and using bright headlights), road-related factors (broken roads, unplanned curves and angles, the need for spacious streets and the lack of appraisal of previous crash records) and traffic control factors (stringent traffic rules, effective implementation and training on using speed guns). CONCLUSION: The factors related to road traffic injury identified in this study could be used to plan targeted interventions for road safety improvement.

Factors associated with low childhood immunization coverage among Rohingya refugee parents in Cox's Bazar, Bangladesh.

INTRODUCTION: Immunization campaigns and Expanded Program on Immunization (EPI) were launched by Government of Bangladesh (GoB) in collaboration with WHO and other Non-governmental Organizations (NGOs) to tackle the increased risk of vaccine preventable disease outbreak in the Rohingya refugee camps. Immunization coverage was found to be lower than expected. However, a few studies explored the factors behind low vaccine uptake among Refugee children. Therefore, this study was aimed. METHODS: A cross sectional study was carried out among Rohingya parents living in registered camps and makeshift settlements located in Teknaf and Ukhiya upazilla of Cox's Bazar, Bangladesh. A total of 224 Rohingya parents were conveniently selected (122 parents from each type of camps). Data was collected using a pretested interviewer-administered semi-structured questionnaire with the help of bilingual volunteers who understand Rohingya dialect. All statistical analyses were carried out in IBM SPSS Version 26 (New York, USA). RESULTS: Total 63.1% of Rohingya parents had good practice regarding childhood immunization (completed EPI vaccination) as per schedule. Of all, 74.6% had good knowledge and 94.7% had positive attitude towards EPI vaccination. Good practice regarding vaccination was significantly more common among parents living in registered camps (77%) than those living in makeshift settlements (49.2%, p<0.001). Multivariable logistic regression analysis revealed that living in registered camps (Adjusted Odds Ratio [aOR]: 2.99; 95% Confidence Interval [CI]: 1.41-6.32) and good knowledge level (aOR: 2.88; 95%CI: 1.32-15.82) were independent determinants of good practice. A separate analysis in both type of camps revealed that in registered camps, good knowledge level (aOR: 3.62; 95%CI: 1.45-9.04) and having >2 children (aOR: 3.71; 95%CI: 1.34-10.27), and in makeshift settlements, father's employment (aOR: 2.33; 95%CI: 1.34-6.72), father's education (aOR: 3.00; 95%CI: 1.34-6.72) and presence of any electronic device (e.g., radio, television, mobile phone) (aOR: 4.01; 95%CI: 0.96-16.84) were significant determinants of good childhood immunization practice. CONCLUSION: Health education and promotion strategies should be implemented to increase knowledge and awareness about EPI immunization benefits among Rohingya parents to ensure greater coverage.

Trends in nephrology referral patterns for patients with chronic kidney disease: Retrospective cohort study.

INTRODUCTION: Information on early, guideline discordant referrals in nephrology is limited. Our objective was to investigate trends in referral patterns to nephrology for patients with chronic kidney disease (CKD). METHODS: Retrospective cohort study of adults with ≥1 visits to a nephrologist from primary care with ≥1 serum creatinine and/or urine protein measurement <180 days before index nephrology visit, from 2006 and 2019 in Alberta, Canada. Guideline discordant referrals were those that did not meet ≥1 of: Estimated glomerular filtration rate (eGFR) ˂ 30 mL/min/1.73m2, persistent albuminuria (ACR ≥ 300 mg/g, PCR ≥ 500 mg/g, or Udip ≥ 2+), or progressive and persistent decline in eGFR until index nephrology visit (≥ 5 mL/min/1.73m2). RESULTS: Of 69,372 patients with CKD, 28,518 (41%) were referred in a guideline concordant manner. The overall rate of first outpatient visits to nephrology increased from 2006 to 2019, although guideline discordant referrals showed a greater increase (trend 21.9 per million population/year, 95% confidence interval 4.3, 39.4) versus guideline concordant referrals (trend 12.4 per million population/year, 95% confidence interval 5.7, 19.0). The guideline concordant cohort were more likely to be on renin-angiotensin system blockers or beta blockers (hazard ratio 1.14, 95% confidence interval 1.12, 1.16), and had a higher risk of CKD progression (hazard ratio 1.09, 95% confidence interval 1.06, 1.13), kidney failure (hazard ratio 7.65, 95% confidence interval 6.83, 8.56), cardiovascular event (hazard ratio 1.40, 95% confidence interval 1.35,1.45) and mortality (hazard ratio 1.58, 95% confidence interval 1.52, 1.63). CONCLUSIONS: A significant proportion nephrology referrals from primary care were not consistent with current guideline-recommended criteria for referral. Further work is needed to identify quality improvement initiatives aimed at enhancing referral patterns of patients with CKD.

The impact of community-based non-pharmacological interventions on cardiovascular and kidney disease outcomes in remote dwelling Indigenous communities: A scoping review protocol.

INTRODUCTION: Indigenous people represent approximately 5% of the world's population. However, they often have a disproportionately higher burden of cardiovascular disease (CVD) risk and chronic kidney disease (CKD) than their equivalent general population. Several non-pharmacological interventions (e.g., educational) have been used to reduce CVD and kidney disease risk factors in Indigenous groups. The aim of this paper is to describe the protocol for a scoping review that will assess the impact of non-pharmacological interventions carried out in Indigenous and remote dwelling populations to reduce CVD risk factors and CKD. MATERIALS AND METHODS: This scoping review will be guided by the methodological framework for conducting scoping studies developed by Arksey and O'Malley. Both empirical (Medline, Embase, Cochrane Library, CINAHL, ISI Web of Science and PsycINFO) and grey literature references will be assessed if they focused on interventions targeted at reducing CVD or CKD among Indigenous groups. Two reviewers will independently screen references in consecutive stages of title/abstract screening and then full-text screening. Impact of interventions used will be assessed using the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework. A descriptive overview, tabular summaries, and content analysis will be carried out on the extracted data. ETHICS AND DISSEMINATION: This review will collect and analyse evidence on the impact of interventions of research carried out to reduce CVD and CKD among Indigenous populations. Such evidence will be disseminated using traditional approaches that includes open-access peer-reviewed publication, scientific presentations, and a report. Also, we will disseminate our findings to the government and Indigenous leaders. Ethical approval will not be required for this scoping review as the data used will be extracted from already published studies with publicly accessible data.

Impact of Home Telemonitoring and Management Support on Blood Pressure Control in Nondialysis CKD: A Systematic Review and Meta-Analysis.

Background: Hypertension is a major cause of cardiovascular disease, chronic kidney disease (CKD), and death. Several studies have demonstrated the efficacy of home blood pressure telemonitoring (HBPT) for blood pressure (BP) control and outcomes, but the effects of this intervention remain unclear in patients with CKD. Objective: To determine the impact of HBPT on cardiovascular-related and kidney disease-related outcomes in patients with CKD. Design: Systematic review and meta-analysis. Setting: All studies that met our criteria regardless of country of origin. Participants: Patients with chronic kidney disease included in studies using HBPT for BP assessment and control. Measurements: Descriptive and quantitative analysis of our primary and secondary outcomes. Methods: We searched MEDLINE, Embase, CINAHL Plus, PsycINFO, Cochrane CENTRAL, Web of Science, and gray literature from inception for observational and randomized controlled studies in nondialysis (ND) CKD using HBPT for BP control. We selected studies that used HBPT as intervention (with or without a control arm) for BP control in ND-CKD populations. The primary outcome was change in mean systolic BP (SBP) and mean diastolic BP (DBP). Results: We selected 7 studies from 1669 articles that were initially identified. Overall, pooled estimates in the mean difference (MD) for SBP and DBP were -8.8 mm Hg; 95% confidence interval (CI): -16.2 to -1.4; P = .02 and -2.4 mm Hg; 95% CI: -3.8 to -1.0; P < .001, respectively. For studies comparing intervention with usual care (UC), pooled estimate in MD for SBP was -8.0 mm Hg (P = .02) with no significant reduction for DBP (-2.6 mm Hg; P = .18). In studies without a UC arm, both SBP and DBP were not significantly reduced (P > .05). The pooled estimate in MD for estimated glomerular filtration rate showed a significant improvement (5.4 mL/min/1.73 m2; P < .001). Limitations: Heterogeneity and few available studies for inclusion limited our ability to identify a robust link between HBPT use and BP and kidney function improvement. Conclusion: Home blood pressure telemonitoring is associated with mild lowering of BP and moderately improved kidney function in patients with CKD. However, larger studies with improved designs and prolonged interventions are still needed to assess the effects of HBPT on patients' outcomes. PROSPERO registration ID: CRD42020190705.

Contexte: L'hypertension est une cause majeure de maladie cardiovasculaire, d'insuffisance rénale chronique (IRC) et de mortalité. Plusieurs études ont montré l'efficacité de la télésurveillance de la pression artérielle à domicile (TSPA) pour le contrôle de la pression artérielle (PA) et les évènements cliniques, mais les effets de cette intervention demeurent mal connus chez les patients atteints d'IRC. Objectif: Évaluer l'effet de la TSPA sur les évènements cardiovasculaires et rénaux chez les patients atteints d'IRC. Conception: Revue systématique et méta-analyse. Sources: Toutes les études satisfaisant nos critères, peu importe le pays d'origine. Sujets: Les patients atteints d'IRC inclus dans les études portant sur l'utilisation de la TSPA pour réguler la pression artérielle. Mesures: Analyse descriptive et quantitative de nos résultats primaires et secondaires. Méthodologie: Nous avons consulté les bases de données MEDLINE, embase, CINAHL plus, PsycINFO, Cochrane CENTRAL et Web of Science, de même que la littérature grise depuis leur début, à la recherche des études observationnelles contrôlées et randomisées portant sur l'utilisation de la TSPA pour contrôler la PA chez des patients atteints d'IRC non dialysés. Nous avons sélectionné les études (avec ou sans bras témoin) utilisant l'intervention (TSPA pour contrôler la PA) dans des populations de patients atteints d'IRC non dialysés. Le principal critère d'évaluation était un changement de la pression systolique moyenne (PSM) et de la pression diastolique moyenne (PDM). Résultats: Nous avons retenu sept études parmi les 1 669 articles initialement répertoriés. Dans l'ensemble, les estimations regroupées de la différence moyenne (DM) pour la PSM et la PDM étaient de −8,8 mmHg (IC 95%: −16,2 à −1,4; P = 0,02) et de −2,4 mmHg (IC 95%: −3,8 à −1,0; P < 0,001) respectivement. Dans les études qui comparaient l'intervention aux soins habituels (SH), les estimations regroupées de la DM s'établissaient à −8,0 mmHg (P = 0,02) pour la PSM, sans réduction significative pour la PDM (−2,6 mmHg; P = 0,18). Dans les études sans bras SH, aucune réduction significative n'a été observée pour la PSM et la PDM (P > 0,05). L'estimation groupée de la DM pour le débit de filtration glomérulaire estimé (DFGe) a montré une amélioration significative (5,4 ml/min/1,73 m2; P < 0,001). Limites: Le peu d'études disponibles pour inclusion et leur hétérogénéité limitent notre capacité à établir un lien robuste entre l'utilisation de la TSPA et une amélioration de la PA et de la fonction rénale. Conclusion: La TSPA est associée à une légère baisse de la PA et à une amélioration modérée de la fonction rénale chez les patients atteints d'IRC. Des études de plus grande envergure, avec des conceptions améliorées et des interventions prolongées, sont nécessaires pour mieux évaluer les effets de la TSPA sur les résultats des patients.

Impact of quality improvement initiatives to improve CKD referral patterns: a systematic review protocol.

INTRODUCTION: Chronic kidney disease (CKD) is a global-health problem. A significant proportion of referrals to nephrologists for CKD management are early and guideline-discordant, which may lead to an excess number of referrals and increased wait-times. Various initiatives have been tested to increase the proportion of guideline-concordant referrals and decrease wait times. This paper describes the protocol for a systematic review to study the impacts of quality improvement initiatives aimed at decreasing the number of non-guideline concordant referrals, increasing the number of guideline-concordant referrals and decreasing wait times for patients to access a nephrologist. METHODS AND ANALYSIS: We developed this protocol by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (2015). We will search the following empirical electronic databases: MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, PsycINFO and grey literature for studies designed to improve guideline-concordant referrals or to reduce unnecessary referrals of patients with CKD from primary care to nephrology. Our search will include all studies published from database inception to April 2021 with no language restrictions. The studies will be limited to referrals for adult patients to nephrologists. Referrals of patients with CKD from non-nephrology specialists (eg, general internal medicine) will be excluded. ETHICS AND DISSEMINATION: Ethics approval will not be required, as we will analyse data from studies that have already been published and are publicly accessible. We will share our findings using traditional approaches, including scientific presentations, open access peer-reviewed platforms, and appropriate government and public health agencies. PROSPERO REGISTRATION NUMBER: CRD42021247756.

Telemonitoring and Case Management for Hypertensive and Remote-Dwelling Patients With Chronic Kidney Disease-The Telemonitoring for Improved Kidney Outcomes Study (TIKO): A Clinical Research Protocol.

BACKGROUND: Hypertension, together with poorly controlled blood pressure (BP) are known risk factors for kidney disease and progression to kidney failure as well as increased cardiovascular (CV) morbidity and mortality. Several studies in patients without kidney disease have demonstrated the efficacy of home BP telemonitoring (HBPT) for BP control. OBJECTIVE: The primary aim of this study is to assess the mean difference in systolic BP (SBP) at 12 months, from baseline in remote dwelling patients with hypertension and chronic kidney disease (CKD) in Northern Alberta, Canada, comparing HBPT + usual care versus HBPT + a case manager. Other secondary objectives, including cost-effectiveness and acceptability of HBPT as well as occurrence of adverse events will also be assessed. DESIGN: This study is designed as a pragmatic randomized controlled trial (RCT) of HBPT plus clinical case management compared to HBPT with usual care. SETTING: Peace River region in Northern Alberta Region, Canada. PATIENTS: Primary care patients with CKD and hypertension. MEASUREMENTS: Eligible patients will be randomized 1:1 to HBPT + BP case management versus HBPT + usual care. In the intervention arm, BP will be measured 4 times daily for 1 week, with medications titrated up or down by the study case manager until guideline targets (systolic BP [SBP]: <130 mmHg) are achieved. Once BP is controlled, (ie, to guideline-concordant targets), this 1-week protocol will be repeated every 3 months for 1 year. Patients in the control arm will also follow the same BP measurement protocol; however, there will be no interactions with the case manager; they will share their BP readings with their primary care physicians or nurse practitioners at scheduled visits. LIMITATIONS: Potential limitations of this study include the relatively short duration of follow-up, possible technological pitfalls, and need for patients to own a smartphone and have access to the internet to participate. CONCLUSIONS: As this study will focus on a high-risk population that has been characterized by a large care gap, it will generate important evidence that would allow targeted and effective population-level strategies to be implemented to improve health outcomes for high-risk hypertensive CKD patients in Canada's remote communities. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT number: NCT04098354).

CONTEXTE: L'hypertension et la pression artérielle (PA) mal contrôlée sont des facteurs de risque reconnus pour la néphropathie et la progression vers l'insuffisance rénale, en plus de poser un risque accru de morbidité et de mortalité cardiovasculaires. Plusieurs études chez des patients sans néphropathie ont démontré l'efficacité de la télésurveillance de la PA à domicile (TSPA) pour le contrôle de la PA. OBJECTIFS: Le principal objectif est d'évaluer la différence moyenne de pression artérielle systolique (PAS) après 12 mois par rapport à sa valeur initiale chez des patients atteints d'hypertension et d'insuffisance rénale chronique (IRC) habitant les communautés éloignées du nord de l'Alberta (Canada). Cet objectif sera atteint en comparant la TSPA + soins habituels à la TSPA + gestionnaire de cas. D'autres objectifs secondaires, notamment le rapport coût/efficacité de la TSPA, son acceptation et la survenue d'événements indésirables seront également évalués. TYPE D'ÉTUDE: Cette étude est conçue comme un essai randomisé contrôlé (ERC) pragmatique comparant la TSPA + prise en charge clinique des cas à la TSPA + soins habituels. CADRE: Région de Peace River dans le nord de l'Alberta (Canada). SUJETS: Patients atteints d'IRC et d'hypertension recevant des soins de santé primaires. MESURES: Les patients admissibles seront répartis 1:1 dans le groupe TSPA + prise en charge du cas d'hypertension ou dans le groupe témoin (TSPA + soins habituels). Dans le groupe d'intervention, la PA sera mesurée quatre fois par jour pendant une semaine, avec augmentation ou réduction de la médication par le gestionnaire de cas de l'étude jusqu'à ce que la cible de référence (PAS : <130 mmHg) soit atteinte. Une fois la PA contrôlée (c.-à-d. conforme aux cibles recommandées), ce protocole sur une semaine sera répété tous les trois mois pendant un an. Les patients du groupe témoin suivront le même protocole de mesure de la PA, mais sans interactions avec le gestionnaire de cas, ils transmettront plutôt leurs mesures de PA à leur médecin de soins primaires ou aux infirmières praticiennes lors de visites prévues. LIMITES: Cette étude est notamment limitée par la durée relativement courte du suivi, de possibles difficultés technologiques et la nécessité pour les participants de posséder un téléphone intelligent et d'avoir accès à l'Internet. CONCLUSION: Puisque cette étude se penchera sur une population à risque élevé et marquée par d'importantes lacunes en matière de soins, elle générera des données importantes qui aideront à mettre en œuvre des stratégies ciblées et efficaces au niveau de la population afin d'améliorer les évènements cliniques des patients hypertendus et atteints d'IRC à haut risque habitant les communautés éloignées au Canada.

Melatonin Modulates Plant Tolerance to Heavy Metal Stress: Morphological Responses to Molecular Mechanisms.

Heavy metal toxicity is one of the most devastating abiotic stresses. Heavy metals cause serious damage to plant growth and productivity, which is a major problem for sustainable agriculture. It adversely affects plant molecular physiology and biochemistry by generating osmotic stress, ionic imbalance, oxidative stress, membrane disorganization, cellular toxicity, and metabolic homeostasis. To improve and stimulate plant tolerance to heavy metal stress, the application of biostimulants can be an effective approach without threatening the ecosystem. Melatonin (N-acetyl-5-methoxytryptamine), a biostimulator, plant growth regulator, and antioxidant, promotes plant tolerance to heavy metal stress by improving redox and nutrient homeostasis, osmotic balance, and primary and secondary metabolism. It is important to perceive the complete and detailed regulatory mechanisms of exogenous and endogenous melatonin-mediated heavy metal-toxicity mitigation in plants to identify potential research gaps that should be addressed in the future. This review provides a novel insight to understand the multifunctional role of melatonin in reducing heavy metal stress and the underlying molecular mechanisms.

Prevalence of polypharmacy and associated adverse health outcomes in adult patients with chronic kidney disease: protocol for a systematic review and meta-analysis.

BACKGROUND: Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population. METHODS/DESIGN: We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran's Q and I2 index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity). DISCUSSION: Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: [ CRD42020206514 ].