Experiences of living kidney donors: A synthesis of unsolicited patient narratives.

INTRODUCTION: Despite the lauded benefits of living kidney donation, there is growing evidence of the challenges that living kidney donors (LKD) encounter in their donation trajectory and gaps in healthcare service provision. However, most of the evidence is derived from research conducted by clinicians or academic investigators. Significantly less attention has been devoted to analyzing unsolicited accounts of LKDs' experiences. METHODS: We conducted a review and synthesis of published unsolicited first-person narratives of LKDs and aimed to synthesize their experiences and identify care needs. Four electronic databases were searched and 27 LKD narratives were included in our final analysis. Thematic synthesis was used to generate themes inductively. RESULTS: Although the majority of LKDs reported the act of donation to be a fulfilling experience, almost 48% reported encountering challenges in the care that they received. Also, 29% of LKDs reported experiencing an adverse clinical event. Five distinct themes emerged surrounding the donation experience and healthcare needs: 1) Educational needs due to perceived lack of transparency and compensating for knowledge gaps; 2) Respect for donor autonomy due to coercive influences from family or healthcare providers, lack of respect for donor preferences and loopholes in the consent process; 3) Unmet care needs related to poor communication with healthcare providers, coordination issues and inconsistent and inadequate long-term care; 4) Unanticipated outcomes due to economic costs and the emotional burden of donation; and 5) Contributing beyond the donation event by advocating for a balanced view of donation and generating support mechanisms. CONCLUSION: In this synthesis of LKDs narratives, important care gaps and the need to advocate for a balanced perspective on living kidney donation were highlighted. Our review underscores the value of patients' own stories as critical evidence that can inform improvement in healthcare service delivery.

Perspectives and experiences of kidney transplant recipients with graft failure: A systematic review and meta-synthesis.

BACKGROUND: Kidney transplant recipients with graft failure are a rapidly rising cohort of patients who experience high morbidity, mortality, and fragmented transitions of care between transplant and dialysis teams. Current approaches to improving care focus on medical and surgical interventions, increasing re-transplantation, and improving coordination between treating teams with little understanding of patient needs and perspectives. METHODS: We undertook a systematic literature review of personal experiences of patients with graft failure. Six electronic and five grey literature databases were searched systematically. Of 4664 records screened 43 met the inclusion criteria. Six empirical qualitative studies and case studies were included in the final analysis. Thematic synthesis was used to combine data that included the perspectives of 31 patients with graft failure and 9 caregivers. RESULTS: Using the Transition Model, we isolated three interconnected phases as patients transition through graft failure: shattering of lifestyle and plans associated with a successful transplant; physical and psychological turbulence; and re-alignment by learning adaptive strategies to move forward. Critical factors affecting coping included multi-disciplinary healthcare approaches, social support, and individual-level factors. While clinical transplant care was evaluated positively, participants identified gaps in the provision of information and psychosocial support related to graft failure. Graft failure had a profound impact on caregivers especially when they were living donors. CONCLUSIONS: Our review reports patient-identified priorities for improving care and can help inform research and guideline development that strives to improve the care of patients with graft failure.

Docetaxel as a Model Compound to Promote HDL (High-Density Lipoprotein) Biogenesis and Reduce Atherosclerosis.

The recent identification of the cell-surface protein DSC1 (desmocollin 1) as a negative regulator of HDL (high-density lipoprotein) biogenesis has attracted us to revisit the old HDL biogenesis hypothesis: HDL biogenesis reduces atherosclerosis. The location and function of DSC1 suggest that DSC1 is a druggable target for the promotion of HDL biogenesis, and the discovery of docetaxel as a potent inhibitor of the DSC1 sequestration of apolipoprotein A-I has provided us with new opportunities to test this hypothesis. The FDA-approved chemotherapy drug docetaxel promotes HDL biogenesis at low-nanomolar concentrations that are far lower than used in chemotherapy. Docetaxel has also been shown to inhibit atherogenic proliferation of vascular smooth muscle cells. In accordance with these atheroprotective effects of docetaxel, animal studies have shown that docetaxel reduces dyslipidemia-induced atherosclerosis. In the absence of HDL-directed therapies for atherosclerosis, DSC1 constitutes an important new target for the promotion of HDL biogenesis, and the DSC1-targeting compound docetaxel serves as a model compound to prove the hypothesis. In this brief review, we discuss opportunities, challenges, and future directions for using docetaxel in the prevention and treatment of atherosclerosis.

Strongyloides stercoralis prevalence in solid-organ and haematopoietic stem cell transplant candidates and recipients: a systematic review and meta-analysis protocol.

INTRODUCTION: Strongyloides stercoralis is an intestinal helminth ubiquitous in tropical and subtropical regions worldwide. It persists in the human host for a lifetime as a result of autoinfection and if undetected and untreated, can lead to increased morbidity and high mortality in immunocompromised individuals such as the transplant population. Transplant patients, including solid-organ and haematopoietic stem cell transplants (SOT and HSCT, respectively), are at a high risk of hyperinfection and disseminated strongyloidiasis. Unfortunately screening is often not systematically performed. Prevalence estimates of Strongyloides in this high-risk population is not well studied. Through this systematic review, we aim to summarise the descriptive evidence on Strongyloides prevalence in SOT and HSCT patients, including diagnostic and screening practices alongside the cases of hyperinfection, disseminated strongyloidiasis and the mortality rate in this population. METHODS AND ANALYSES: Through the use of various online library databases, we will conduct a systematic review including relevant literature on the prevalence of Strongyloides in SOT and HSCT patients as well as studies assessing hyperinfection and disseminated strongyloidiasis in this patient population. The Population, Intervention, Comparison, Outcome and Study Design strategy and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be used to determine a final subset of studies for analysis. Quality assessment for case series and case reports will be determined by a modified quality assessment tool developed by the National Heart, Lung, and Blood Institute (NIH), and the CARE guidelines, respectively. We will provide a narrative synthesis of the findings pertaining to the primary and secondary outcomes of interest (prevalence of Strongyloides and mortality rate in transplant population, respectively) alongside the associated 95% CI. Estimates from individual studies will be pooled using a random effects model. ETHICS AND DISSEMINATION: This systematic review does not require formal ethical approval since no primary data will be collected. Findings will be disseminated through a peer-reviewed publication and relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42021269305.

Aortic stenosis in homozygous familial hypercholesterolaemia: a paradigm shift over a century.

AIMS: Homozygous familial hypercholesterolaemia (HoFH) is an orphan disease defined by extreme elevations in low-density lipoprotein cholesterol, cutaneous xanthomas, and pre-mature atherosclerotic cardiovascular disease. Survival has more than doubled over the past three decades. Aortic stenosis (AS) [supravalvular aortic stenosis (SVAS) or valvular aortic stenosis (VAS)] is commonly encountered. There are no medical treatments available and complex high-risk surgeries represent the only available option in severe cases. A systematic review was performed to summarize the current evidence on AS in HoFH and to determine whether pharmacological treatment (statins) have had an impact on clinical presentation, phenotype and clinical course over the past nine decades (PROSPERO CRD42021250565). METHODS AND RESULTS: MEDLINE, Embase Classic + Embase, Cochrane Central Register of Controlled Trials, PubMed, AfricaWide, and Scopus were searched from inception to 10 November 2021. Searches identified 381 publications, of which 19 were retained; they were cross-sectional or retrospective studies. Separately, 108 individual case reports were described. Within the 424 HoFH cases, AS was identified in 57% of patients in the pre-statin era vs. 35% in patients reported more recently (>2000, long-term statin period). With an increase in longevity due to statins and lipoprotein apheresis, a change in the proportion of patients with SVAS and VAS with a SVAS:VAS ratio of 47:53 and 10:90 for HoFH patients not on statin and on long-term statin, respectively, was noted. CONCLUSION: These data suggest that SVAS and VAS are frequent in HoFH and that the phenotype has shifted towards calcific VAS as statins and lipoprotein apheresis improve survival in these patients.

Arterial stiffness measurements in pregnancy as a predictive tool for hypertensive disorders of pregnancy and preeclampsia: Protocol for a systematic review and meta-analysis.

Hypertensive disorders of pregnancy (HDPs) are a leading cause of maternal morbidity and mortality worldwide. Unfortunately, accurate early clinical screening methods for the development of these disorders are lacking. Arterial stiffness (AS) is an important hemodynamic indicator of vascular health that has shown promising results for the prediction of HDP onset. Past systematic reviews in the field have reported an increase in AS indices in women who develop HDPs and have highlighted the potential of AS measurements as a predictive tool early in pregnancy. The most recent systematic review, including papers up to 2015, assessed the differences in AS parameters between women with and without pregnancy complications. Since then, there has been a substantial influx of published research on the topic and a growing interest in the incorporation of AS measurements into clinical practice. Thus, we propose a systematic review and meta-analysis that is more inclusive to all HDP subsets and various hemodynamic indices of vascular health to provide a comprehensive overview of the current state of evidence. Specifically, we aim to evaluate these measures in women who develop HDPs compared to normotensive pregnancies to determine which measures are most associated with and/or can predict the development of HDPs. Major databases (Medline, Embase, The Cochrane Library, Web of Science, PubMed, and CINAHL), grey literature (Google Scholar) and clinical trials (clinicaltrials.gov) will be searched to identify studies that report AS and hemodynamic measurements in pregnant women with and without HDPs. No restrictions will be made on study type or year. Articles will be independently evaluated by three authors to determine eligibility based on inclusion and exclusion criteria. Methodological quality of included studies will be assessed. Pooled analyses will be conducted using a random-effects model. Publication bias and between-study heterogeneity will also be assessed. Sources of heterogeneity will be explored by sensitivity, subgroup, and/or meta-regression analyses. Results from this study will be shared through scientific conferences and publications in scientific journals. The analysis of potential AS and hemodynamic markers for HDP onset will help inform the development of screening guidelines and clinically relevant cut-off values of AS and hemodynamic markers for HDP risk, guiding future research. There are no applicable ethical considerations to the writing of this protocol.

Health-related quality of life in homozygous familial hypercholesterolemia: A systematic review and meta-analysis.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by extreme elevations of low-density lipoprotein cholesterol (LDL-C) and extremely premature atherosclerotic cardiovascular disease. To date, impacts of HoFH and its treatment on the psychosocial wellbeing of patients have been poorly characterized. OBJECTIVES: We performed a systematic review of the association between HoFH and health-related quality of life (HRQL). METHODS: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) consensus guidelines. We searched MEDLINE, Embase, The Cochrane Controlled Register of Trials (CENTRAL), Pubmed, Scopus, AfricaWide (via EBSCO), and six trial registries and grey-literature databases from inception to May 2021 for published English-language literature examining HRQL and its determinants in HoFH. Studies were eligible if they included patients with confirmed HoFH and evaluated HRQL using validated tools. We performed a narrative synthesis of qualitative findings from included studies and, where data permitted, random-effects meta-analysis reporting standardized mean differences (SMD) and 95% confidence intervals (CIs). RESULTS: Our review identified seven eligible studies examining HRQL in HoFH participants. Pooling data from two included studies, we found that relative to the general population, HoFH patients demonstrated significantly poorer HRQL in multiple dimensions of the 36-item Short-Form Health Survey (SF-36) with lower scores in physical functioning (SMD -0.37; 95% CI: -0.60, -0.15), role limitations due to physical health (SMD -0.63; 95% CI: -1.24, -0.02), social functioning (SMD -0.61; 95% CI: -1.19, -0.03), bodily pain (SMD -0.24; 95% CI: -0.46, -0.01), and general health (SMD -1.55; 95% CI: -1.80, -1.31). No differences were observed in domains of energy and vitality, mental health and emotional well-being, or role limitations due to emotional problems. Patients suffered high treatment burdens related to lipoprotein apheresis that compromised educational attainment and employment. However, few patients received psychological support in navigating their treatment challenges. No studies evaluated the association of HoFH with incident anxiety, depression, or other psychopathology. CONCLUSIONS: Limited data are available on quality of life for patients with HoFH. The available data suggest that these patients may suffer disease-related impairments in quality of life. Future work should aim to elucidate relationships between HoFH and mental health outcomes and develop interventions to improve quality of life in this population.

Major adverse cardiovascular events in homozygous familial hypercholesterolaemia: a systematic review and meta-analysis.

AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a genetic condition characterized by extremely elevated levels of low-density lipoprotein cholesterol and premature atherosclerotic cardiovascular disease and death. Due to its rarity, accurate assessment of cardiovascular outcomes associated with HoFH and how they have changed over time has been challenging. The goal of this study was to assess the prevalence and age-of-onset of major adverse cardiovascular events (MACE) among patients with HoFH. METHODS AND RESULTS: We searched MEDLINE, EMBASE, Pubmed, Cochrane Central Register of Controlled Trials, Scopus, Africa-Wide, Google Scholar, Open Grey, and various clinical trial registries from inception to February 2020 to identify studies reporting on MACE in HoFH patients. We determined the pooled prevalence and mean age-of-onset of MACE outcomes individually using a random effects inverse variance model. We identified 94 studies that met our eligibility criteria. Myocardial infarction and coronary revascularization were common with a prevalence of 15.1% [95% confidence interval (95% CI) 10.7-20.0] and 28.3% (95% CI 22.5-34.3), respectively. The mean age-of-onset was 24.5 (95% CI 19.2-29.8) years for myocardial infarction and 32.2 (95% CI 26.6-37.8) years for revascularization. Sub-group analyses based on the year of publication revealed significant delays in the onset of MACE outcomes post-1990 compared to pre-1990. Egger's regression suggested possible bias, likely due to small study effects. CONCLUSIONS: Atherosclerotic cardiovascular disease is common among HoFH patients and occurs at a young age. Age-of-onset of myocardial infarction was delayed by more than a decade from pre-1990 to post-1990, likely attributable to widespread use of statins and other therapies, reflecting substantial progress in the management of this rare but severe disorder.

Strategies used to engage hard-to-reach populations in childhood disability research: a scoping review.

PURPOSE: We completed a scoping review to: (1) identify strategies that have been used to engage hard-to-reach populations in childhood disability research, and (2) synthesize information as to whether and how these strategies were evaluated. METHODS: Systematic search of six electronic databases and grey literature to identify articles published in the last 10 years. Studies published in English, French, and Spanish reporting on strategies used to engage hard-to-reach populations in childhood disability research were eligible for inclusion. RESULTS: Out of 106 articles selected for full text review, 16 were included. Engagement was more common in earlier stages of research. The populations included in studies were children with disabilities and their parents. Engagement strategies were reported but rarely evaluated. Anecdotal outcomes of engagement were reported in 14/16 studies and included positive outcomes for the children and parents such as empowerment. The challenges with engagement included the increased time needed to engage children with disabilities or their parents. CONCLUSIONS: Our results can guide others who wish to engage a diverse group of children with disabilities and their parents in research. Research on how to engage other hard-to-reach populations within the childhood disability umbrella and evaluation of engagement strategies and outcomes is needed.IMPLICATIONS FOR REHABILITATION• Service providers should be concerned when the research informing their practices does not include families that represent their clients (e.g., families who are low income, Indigenous, ethnic minority, or LGBTQI parents of children with disabilities).• Strategies used to include children with disabilities in research, such as offering varied response methods that include story telling or photography, may also be used to promote participation in clinical services.• Service providers and teachers may have a role in facilitating the recruitment of 'hard-to-reach' families in research and advising researchers on methods to create a comfortable environment with accessible means of data collection for children with disabilities.

Combined Exercise and Nutrition Optimization for Peripheral Arterial Disease: A Systematic Review.

BACKGROUND: Patients with peripheral arterial disease (PAD) who suffer from claudication have a low exercise capacity, poor quality of life, and often severe disability. Exercise and healthy nutrition have been shown to be important factors to prevent disease progression. This systematic review aims to assess the evidence supporting the use of combined nutrition and structured exercise in patients with intermittent claudication. METHODS: Publications that included a combination of structured exercise (SE) and a nutritional intervention and that reported quality of life, exercise capacity, pain-free walking distance, limb blood flow hemodynamics, need for revascularization surgery, or surgical outcomes were systematically searched. Publications were screened, selected, and reviewed by 2 independent reviewers. RESULTS: Four publications were found reporting the effects of combined SE and nutrition programs. Pooled statistical analysis across trials was not performed because of the heterogeneity of study designs and type of interventions. Only 2 randomized controlled trials were found, reporting conflicting results with regard to the effects of combined SE and nutrition on exercise capacity. Only one trial reported quality of life measures. Blood flow was increased in the intervention involving inorganic nitrate in addition to SE. CONCLUSIONS: There are conflicting results and lack of quality data proving the benefit of nutrition and SE programs on patient-centered outcomes and limb blood flow. There are no data on the effects of combined nutrition and exercise on the need for revascularization surgery or postrevascularization outcomes. More randomized controlled trials are needed to assess the effects of multimodal interventions on patient-centered outcomes and clinical outcomes of PAD.

Sex differences in the efficacy of antihypertensive treatment in preventing cardiovascular outcomes and reducing blood pressure: protocol for a systematic review and meta-analysis.

INTRODUCTION: Hypertension is a leading cause of mortality worldwide and its prevalence is expected to rise over the next decade. Sex differences exist in the epidemiology and pathophysiology of hypertension. It is well established that antihypertensive treatment can significantly reduce the risk for stroke and other cardiovascular disease events. However, it remains unclear whether this effect is dependent on sex. In this protocol, we outlined a systematic review and meta-analysis to evaluate the effects of antihypertensive therapy in (1) reducing blood pressure and (2) preventing cardiovascular morbidity and mortality outcomes for each sex separately. METHODS AND ANALYSIS: The following electronic databases will be searched: Medline, Embase, The Cochrane Library, PubMed, Cumulative Index of Nursing and Allied Health Literature Plus, Web of Science, grey literature (Google Scholar) and several trial registries. Search strategies will be designed to identify human adult (≥18) randomised (and non-randomised) controlled trials, prospective and retrospective cohort studies, and case-control studies concerning 'sex-specific differences associated with the efficacy of antihypertensive treatment'. A preliminary search strategy was developed for Medline (1946-16 September 2019). Two investigators will independently review each article included in the final analysis. Primary outcomes investigated are cardiovascular morbidity and mortality and systolic and diastolic blood pressure. Pooled analyses will be conducted using the random-effects model. Publication bias will be assessed by visual inspection of funnel plots and by Begg's and Egger's statistical tests. Between-studies heterogeneity will be measured using the I2 test (p<0.10). Sources of heterogeneity will be explored by sensitivity, subgroup and metaregression analyses. ETHICS AND DISSEMINATION: This is the first meta-analysis that will comprehensively compare the efficacy of antihypertensive treatment regimens between men and women. Findings will be shared through scientific conferences and societies, social media and consumer advocacy groups. Results will be used to inform the current guidelines for management of hypertension in men and women by demonstrating the importance of implementing sex-specific recommendations. Ethical considerations are not applicable for this protocol.