Centering Public Perceptions on Translating AI Into Clinical Practice: Patient and Public Involvement and Engagement Consultation Focus Group Study.

BACKGROUND: Artificial intelligence (AI) is widely considered to be the new technical advancement capable of a large-scale modernization of health care. Considering AI's potential impact on the clinician-patient relationship, health care provision, and health care systems more widely, patients and the wider public should be a part of the development, implementation, and embedding of AI applications in health care. Failing to establish patient and public engagement and involvement (PPIE) can limit AI's impact. OBJECTIVE: This study aims to (1) understand patients' and the public's perceived benefits and challenges for AI and (2) clarify how to best conduct PPIE in projects on translating AI into clinical practice, given public perceptions of AI. METHODS: We conducted this qualitative PPIE focus-group consultation in the United Kingdom. A total of 17 public collaborators representing 7 National Institute of Health and Care Research Applied Research Collaborations across England participated in 1 of 3 web-based semistructured focus group discussions. We explored public collaborators' understandings, experiences, and perceptions of AI applications in health care. Transcripts were coanalyzed iteratively with 2 public coauthors using thematic analysis. RESULTS: We identified 3 primary deductive themes with 7 corresponding inductive subthemes. Primary theme 1, advantages of implementing AI in health care, had 2 subthemes: system improvements and improve quality of patient care and shared decision-making. Primary theme 2, challenges of implementing AI in health care, had 3 subthemes: challenges with security, bias, and access; public misunderstanding of AI; and lack of human touch in care and decision-making. Primary theme 3, recommendations on PPIE for AI in health care, had 2 subthemes: experience, empowerment, and raising awareness; and acknowledging and supporting diversity in PPIE. CONCLUSIONS: Patients and the public can bring unique perspectives on the development, implementation, and embedding of AI in health care. Early PPIE is therefore crucial not only to safeguard patients but also to increase the chances of acceptance of AI by the public and the impact AI can make in terms of outcomes.

Then there were seven: a commentary on creating a public involvement strategy group for a policy research unit in behavioural science.

The National Institute for Health and Care Research (NIHR) Policy Research Unit in Behavioural Science (PRU-BS) was funded to inform government on the application of behavioural science in health and social care policy. What makes this unit different to other topic specific ones, was the wide range of its brief. Because of this, the PPI group would need to include a wide range of experience and expertise and be prepared to learn. We were a different type of public group for a different type of task. This paper deals with how we approached this. In this paper we outline how the PPI plan in the funding proposal for the PRU-BS was adapted to real world challenges. We describe the stages in the formation of the PPI Strategy Group and how a virtual platform was created to ensure good communication. We discuss our pragmatic approach of developing Terms of Reference and a PPI strategy document. Given the restrictions imposed by the Covid-19 pandemic we explain how we tackled PPI SG member induction sessions, meetings and training sessions. To illustrate how the group operates we provide an example of our involvement in a PRU-BS project. Central to our paper is the lessons we learned. We hope the challenges we met in forming the unique PPI SG, how these were overcome, and our recommendations will help others faced with a similar task.

The Policy Research Unit in Behavioural Science (PRU-BS) was formed in early 2019, funded by the National Institute for Health and Care Research (NIHR). The aim of the unit is to advise the government on the use of behavioural science (the study of human behaviour) to inform health and social care policy. From the outset the aim was to embed PPI in all aspects of the unit's work from the governance and direction of the unit to the individual research projects it conducts. As behavioural science cuts across all aspects of health, recruiting members of the public to work within the PRU-BS required careful thought. In this paper we describe the processes of recruiting to our PPI Strategy Group, the induction and training, and the ways in which we worked to develop the group and become embedded within the unit. Lastly, we present several recommendations based on our experiences of forming the PPI Strategy Group. Although this is aimed primarily at those contemplating setting up a group whose remit extends beyond a single research project, we hope this will be a useful resource for the public, researchers and others working in PPI.

Advancement in CRISPR/Cas9 Technology to Better Understand and Treat Neurological Disorders.

Neurological disorders have complicated pathophysiology that may involve several genetic mutations. Conventional treatment has limitations as they only treat apparent symptoms. Although, personalized medicine is emerging as a promising neuro-intervention, lack of precision is the major pitfall. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system is evolving as a technological platform that may overcome the therapeutic limitations towards precision medicine. In the future, targeting genes in neurological disorders may be the mainstay of modern therapy. The present review on CRISPR/Cas9 and its application in various neurological disorders may provide a platform for its future clinical relevance towards developing precise and personalized medicine.

Pharmacological Strategies for Stroke Intervention: Assessment of Pathophysiological Relevance and Clinical Trials.

OBJECTIVES: The present review describes stroke pathophysiology in brief and discusses the spectrum of available treatments with different promising interventions that are in clinical settings or are in clinical trials. METHODS: Relevant articles were searched using Google Scholar, Cochrane Library, and PubMed. Keywords for the search included ischemic stroke, mechanisms, stroke interventions, clinical trials, and stem cell therapy. RESULTS AND CONCLUSION: Stroke accounts to a high burden of mortality and morbidity around the globe. Time is an important factor in treating stroke. Treatment options are limited; however, agents with considerable efficacy and tolerability are being continuously explored. With the advances in stroke interventions, new therapies are being formulated with a hope that these may aid the ongoing protective and reparative processes. Such therapies may have an extended therapeutic time window in hours, days, weeks, or longer and may have the advantage to be accessible by a majority of the patients.

A Study of Neuromyelitis Optica Spectrum Disorders (NMOSD): Disease Pattern Based on Antibody Status.

Introduction: Neuromyelitis optica (NMO) is a central demyelinating disorder, predominantly affecting the optic nerves and spinal cord and autoimmune basis. We aimed to analyze the clinical, laboratory, and imaging features associated with NMO spectrum disorders (NMOSD) according to the aquaporin 4 antibody (AQP4-Ab) serology status. Methods: The inclusion of the patients was based on the Wingerchuk criteria (2006) for NMO, known antibody status and has minimum 1-year follow-up. We analyzed and compared 46 patients with known antibody status. Results: AQP4-Ab positivity was 56.5%. The male to female ratio in the seropositive group was 1:7.7 and 1:1.2 in the seronegative group. The mean age of onset in seropositive patients was 36.8 years (vs 28.8 years in seronegative NMOSD patients). Clinical feature, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) features were also different, but data from two subsets did not reach statistical significance. The relapse rate was higher in AQP4 positive NMOSD (84.6% vs 55% in the seronegative group). The recovery rate for AQP4 positive patients was poor (15%). Summary: We found differences in age, gender, and prognosis between the two groups. Antibody status may be a guiding factor in deciding the treatment approach during the first attack of NMOSD.

Keyhole Sliding Hip Screw Fixation for Stable Intertrochanteric Hip Fractures: A Novel Technique.

Intertrochanteric hip fractures are common orthopaedic injuries and the incidence is growing with increasing life expectancy. Several randomized controlled studies have shown the advantages of intramedullary devices over hip screw fixation in unstable intertrochanteric fractures. However, the proven advantage of the intramedullary device in stable intertrochanteric fractures, OTA (Orthopaedic Trauma Association) classification 31-A1 and some 31-A2 fractures are in less blood loss compared with standard hip screw fixation. In the current technical note, we describe a novel minimally invasive technique of hip screw fixation that use a keyhole size incision to fix stable intertrochanteric fractures using sliding hip screw. The less invasive nature and potentially reduced blood loss makes this technique an attractive option for stabilizing stable intertrochanteric hip fractures.

Evaluation of one-year effectiveness of clobazam as an add-on therapy to anticonvulsant monotherapy in participants with epilepsy having uncontrolled seizure episodes: An Indian experience.

OBJECTIVES: To prospectively study the effectiveness and safety of clobazam as an add-on therapy in patients with epilepsy whose seizures are not adequately controlled with antiseizure medicine (ASM) monotherapy. METHODS: We conducted a prospective, observational study at 28 neurology outpatient clinics in India from June 2017 to October 2019. Consecutive patients with epilepsy (older than 3 years) with inadequate seizure control with ASM monotherapy were initiated on clobazam. Patients were followed up at 1, 3, 6, 9, and 12 months. Seizure control and adverse events were assessed through personal interviews and seizure diaries. RESULTS: Out of 475 eligible patients, data of 429 patients (men: 65.5%) were evaluated (46 excluded due to protocol deviations). The median age was 25 (range, 3-80 years) years and the median duration of epilepsy was 3 (0.1-30) years. The majority of patients had focal epilepsy (55.0%) and genetic generalized epilepsy (40.1%). The one-year follow-up was completed by 380 (88.5%) patients. At one-year follow-up, 317 (83.4%; N = 380) patients in the study remained seizure free. These 317 patients who were seizure free at 12 months comprised 73.9% of the evaluable population (N = 429). In 98.8% of patients, the primary reason for adding clobazam was inadequate control of seizures with treatment. During one-year follow-up, a total of 113 (22.6%) patients experienced at least one adverse event which included 103 (20.6%) patients who experienced 386 episodes of seizures. CONCLUSION: The study provides preliminary evidence that clobazam is effective and well-tolerated as add-on therapy for a period of one year among patients with epilepsy inadequately stabilized with monotherapy. TRIAL REGISTRATION NUMBER: CTRI/2017/12/010906.

Negative Impact of Vestibular Suppressant Drugs on Provocative Positional Tests of BPPV: A Study from the Western Part of India.

AIMS: To study the impact of vestibular suppressant drugs (VSD) on provocative positional tests (PPT) in patients with benign paroxysmal positional vertigo (BPPV). SETTINGS AND DESIGN: A prospective case-control observational study. MATERIALS AND METHODS: Patients with a history suggestive of BPPV were tested for PPT. Patients with vertiginous symptoms and with nystagmus on PPT were classified as objective BPPV (O-BPPV, control group), while those without nystagmus with no alternate diagnosis were classified as subjective BPPV (S-BPPV, case group). Details of VSD treatment were noted in all the patients. In both groups, patients were instructed to discontinue VSD and were further assigned as the VSD and non-VSD subgroups. Patients were followed for 2 months with PPT every week. PPT positive patients were treated by vestibular rehabilitation maneuvers. STATISTICS: Student t-test with two-tailed, unpaired, was used for continuous scale and Chi-square test for categorical differences between the two groups. RESULTS: 295 consecutive BPPV patients were enrolled in the study, 55 in the S-BPPV group and 240 in the O-BPPV group. Significantly higher proportion of patients in the S-BPPV group were on VSD at presentation, 80.00% vs. 53.75% (OR 2.52; 95% CI: 1.30-4.86), P = 0.006. In an unadjusted analysis of the S-BPPV group following discontinuation of VSD, PPT became positive in 79.54% of patients as compared to 18.19% in the non-VSD group (OR 35.0; 95% CI: 6.2-197.3), P < 0.001. CONCLUSION: A higher proportion of S-BPPV patients were receiving VSD in comparison to O-BPPV at the initial visit. The PPT converted positive four times higher after ceasing the VSD in S-BPPV patients. STUDY DESIGN: Prospective case-control observational study.

Management of Cardiovascular Disease in Kidney Disease Study: Rationale and Design.

INTRODUCTION: Atherosclerosis, inflammation, and vascular stiffness are prominent interrelated risk factors contributing to the high incidence of cardiovascular disease (CVD) in patients with CKD. Conventional CVD management strategies in CKD largely target atherosclerotic CVD and have had a limited impact on the cardiovascular mortality in this population. Multiple in vivo and in vitro studies and epidemiological evidence from the rheumatologic cohorts have shown that low-dose hydroxychloroquine has beneficial effects on inflammation, endothelial function, insulin sensitivity, and metabolic syndrome. Our recent proof-of-concept animal study showed that hydroxychloroquine has marked protection against atherosclerosis and vascular stiffness. We hypothesize that hydroxychloroquine has the potential to provide significant cardiovascular benefits in patients with CKD. METHODS: The Management of Cardiovascular disease in Kidney disease study (NCT03636152) is a phase 2B, randomized, double-blind, placebo-controlled trial evaluating the effects of low-dose hydroxychloroquine therapy on the parameters of atherosclerosis, inflammation, and vascular stiffness in patients with CKD. The study plans to enroll 100 CKD patients estimated to be at high cardiovascular risk by a combination of low estimated glomerular filtration rate and albuminuria and treat them for 18 months with hydroxychloroquine or placebo in 1:1 allocation. RESULTS: The study will assess the change in the total carotid plaque volume as measured by serial noncontrast carotid MRI as the primary outcome and the serial changes in plasma inflammation markers, vascular stiffness, renal function, and the composition characteristics of the carotid plaque as secondary outcome measures. DISCUSSION/CONCLUSION: The results of this trial will provide the proof-of-applicability for hydroxychloroquine in the CVD in CKD. If positive, this trial should lead to phase-3 trials with clinical end points for this potentially transformative, novel, and inexpensive therapy for CVD in CKD.

Assessing Utility of Clinical Exome Sequencing in Diagnosis of Rare Idiopathic Neurodevelopmental Disorders in Indian Population.

BACKGROUND: Neurological diseases are phenotypically and genotypically heterogeneous. Clinical exome sequencing (CES) has been shown to provide a high diagnostic yield for these disorders in the European population but remains to be demonstrated for the Indian population. OBJECTIVE: The study aimed to understand the utility of clinical exome sequencing for the diagnosis of neurodevelopmental disorders. MATERIALS AND METHODS: A cohort of 19 idiopathic patients with neurological phenotypes, primarily intellectual disability and developmental delay, were recruited. CES covering 4620 genes was performed on all patients. Candidate variants were validated by Sanger sequencing. RESULTS: CES in 19 patients provided identified 21 variants across 16 genes which have been associated with different neurological disorders. Fifteen variants were reported previously and 6 variants were novel to our study. Eleven patients were diagnosed with autosomal dominant de novo variants, 7 with autosomal recessive and 1 with X-linked recessive variants. CES provided definitive diagnosis to 10 patients; hence, the diagnostic yield was 53%. CONCLUSION: Our study suggests that the diagnostic yield of CES in the Indian population is comparable to that reported in the European population. CES together with deep phenotyping could be a cost-effective way of diagnosing rare neurological disorders in the Indian population.

Home run-results of a chronic kidney disease Telemedicine Patient Education Study.

BACKGROUND: Chronic kidney disease (CKD) incidence is increasing and associated mortality and morbidity are high. Educating patients is effective in delaying progression and establishing optimal renal replacement therapy (RRT). Tele-education/telemedicine (TM) can be an effective tool to provide such education, but there are no available data quantifying its effectiveness. We attempted to establish such evidence correlating the effect of education in patient choices and with the start of actual RRT. We present results from a 3-year pilot study evaluating the effectiveness of comprehensive predialysis education (CPE) through TM for CKD patients compared with a standard care group [face to face (FTF)]. The patient's ability to choose RRT was the primary endpoint. METHODS: This was a randomized controlled study providing CPE over three classes at nine sites (one FTF and eight TM). Three assessment tools were utilized to compare groups: CKD knowledge, literacy and quality of life. RESULTS: A total of 47.1% of FTF and 52.2% of TM patients reported not having enough information to choose a modality. This decreased by the third visit (FTF 7.4%, TM 13.2%). Home modality choices more than doubled in both groups (FTF 25.8-67.7%, TM 22.2-50.1%). In patients that completed one visit and needed to start RRT, 47% started on a home modality or received a pre-emptive transplant (home hemodialysis 6%, peritoneal dialysis 38%, transplant 3%). CONCLUSIONS: Results show almost 90% (TM 87%, FTF 95%) of the attendees could choose a modality after education. Home modality choices doubled. Patients were able to make an informed choice regardless of the modality of education.

The SARS-CoV-2/COVID-19 pandemic and challenges in stroke care in India.

Stroke care in India has evolved rapidly in the last decade with a focus on stroke awareness, prevention, rapid triage, treatment, and rehabilitation. But acute stroke care and poststroke rehabilitation in the country have limitations owing to the economic constraints and poor access to health care. The SARS-CoV-2/COVID-19 pandemic has made stroke care even more challenging. We outline the unfavorable circumstances in stroke care induced by the pandemic; propose mitigating measures; crisis management; and provide a comparative evaluation of stroke care between India and the United States during the pandemic. There is a need for public health systems in both developed and developing countries to improve awareness, implement proper strategies of triage, acute treatment, well-defined rehabilitation plans, telemedicine services, and virtual check-ins.

Autophagy Function and Regulation in Kidney Disease.

Autophagy is a dynamic process by which intracellular damaged macromolecules and organelles are degraded and recycled for the synthesis of new cellular components. Basal autophagy in the kidney acts as a quality control system and is vital for cellular metabolic and organelle homeostasis. Under pathological conditions, autophagy facilitates cellular adaptation; however, activation of autophagy in response to renal injury may be insufficient to provide protection, especially under dysregulated conditions. Kidney-specific deletion of Atg genes in mice has consistently demonstrated worsened acute kidney injury (AKI) outcomes supporting the notion of a pro-survival role of autophagy. Recent studies have also begun to unfold the role of autophagy in progressive renal disease and subsequent fibrosis. Autophagy also influences tubular cell death in renal injury. In this review, we reported the current understanding of autophagy regulation and its role in the pathogenesis of renal injury. In particular, the classic mammalian target of rapamycin (mTOR)-dependent signaling pathway and other mTOR-independent alternative signaling pathways of autophagy regulation were described. Finally, we summarized the impact of autophagy activation on different forms of cell death, including apoptosis and regulated necrosis, associated with the pathophysiology of renal injury. Understanding the regulatory mechanisms of autophagy would identify important targets for therapeutic approaches.

Long-term Adverse Events Associated With Acute Kidney Injury.

Acute kidney injury (AKI) occurs in approximately 10% to 15% of hospital-admitted patients and is associated with in-hospital mortality of 50% in patients requiring renal replacement therapy. Recently, multiple observational studies have demonstrated that patients who survive AKI have significant long-term consequences including cardiovascular events, progression to advanced-stage chronic kidney disease (CKD), and mortality. A direct link between AKI and CKD is provided by studies that demonstrate that some patients with normal renal function who develop AKI requiring dialysis never recover. In addition, in a large pediatric AKI population, 10% of the cohort developed CKD within 1 to 3 years. In a systemic review and meta-analysis in which 13 cohort studies were analyzed, patients with AKI had a hazard ratio (HR) of 8.8 for developing CKD, HR of 3.1 of developing end-stage kidney disease, and HR of 2.0 for mortality. AKI was also independently associated with risk for cardiovascular disease and congestive heart failure. These studies indicate that AKI is associated with important, long-term consequences and that AKI has become an important contributor to the end-stage kidney disease population. Prospective ongoing studies will better define the cause-effect relationship and delineate potential biomarkers that would identify AKI patients at risk for CKD, cardiovascular events, and mortality.

Effects of a Comprehensive Predialysis Education Program on the Home Dialysis Therapies: A Retrospective Cohort Study.

BACKGROUND: Improvement in the rates of home dialysis has been a desirable but difficult-to-achieve target for United States nephrology. Provision of comprehensive predialysis education (CPE) in institutes with established home dialysis programs has been shown to facilitate a higher home dialysis choice amongst chronic kidney disease (CKD) patients. Unfortunately, limited data have shown the efficacy of such programs in the United States or in institutes with small home dialysis (HoD) programs. METHODS: We report the retrospective findings examining the efficacy of a CPE program in the early period after its establishment, with reference to its impact on the choice and growth of a small HoD program. RESULTS: Over the initial 22 months since its inception, 108 patients were enrolled in the CPE clinic. Seventy percent of patients receiving CPE chose HoD, of which 55% chose peritoneal dialysis (PD) and 15% chose home hemodialysis (HHD). Rates of HoD choice were similar across the spectrum of socio-economic variables. Of just over half (54.6%) of those choosing to return for more than 1 session, 25.3%, changed their modality preference after the first education session, and nearly all reached a final modality selection by the end of the third visit. Initiation of the CPE program resulted in a 216% growth in HoD census over the same period and resulted in near doubling of HoD prevalence to 38% of all dialysis patients. CONCLUSIONS: Comprehensive patient education improves the choice and prevalence of HoD therapies. We further find that 3 sessions of CPE may provide needed resources for the large majority of subjects for adequate decision-making.

Carbamylated Low-Density Lipoprotein (cLDL)-Mediated Induction of Autophagy and Its Role in Endothelial Cell Injury.

Patients with chronic kidney disease (CKD) have high risk of cardiovascular complications. Plasma levels of carbamylated proteins produced by urea-derived isocyanate or thiocyanate are elevated in CKD patients and that they are significant predictors of cardiovascular events and all-cause mortality. Carbamylated LDL (cLDL) has pro-atherogenic properties and is known to affect major biological processes relevant to atherosclerosis including endothelial cell injury. The underlying mechanisms of cLDL-induced endothelial cell injury are not well understood. Although autophagy has been implicated in atherosclerosis, cLDL-mediated induction of autophagy and its role in endothelial cell injury is unknown. Our studies demonstrate that human coronary artery endothelial cells (HCAECs) respond to cLDL by specific induction of key autophagy proteins including LC3-I, beclin-1, Atg5, formation of lipid-conjugated LC3-II protein, and formation of punctate dots of autophagosome-associated LC3-II. We demonstrated that autophagy induction is an immediate response to cLDL and occurred in a dose and time-dependent manner. Inhibition of cLDL-induced autophagy by a specific siRNA to LC3 as well as by an autophagy inhibitor provided protection from cLDL-induced cell death and DNA fragmentation. Our studies demonstrate that autophagy plays an important role in cLDL-mediated endothelial cell injury and may provide one of the underlying mechanisms for the pathogenesis of cLDL-induced atherosclerosis in CKD patients.

Combined Central and Peripheral Demyelination.

Demyelinating disorders are very common, but remains isolated to the part of nervous system they involve. However, infrequently, combined involvement of central and peripheral nervous system with demyelinating process have been described. We report one such rare case, with possible theories of common etiological basis. We present a middle aged male patient with Chronic Inflammatory Demyelinating Polyneuropathy(CIDP), who responded to immuno-modulation. Subsequently, he developed Acute Transverse Myelitis (ATM). Recently a common substrate protein, NF186 has been described as responsible for this rare clinical entity.

Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial.

BACKGROUND AND OBJECTIVES: Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 µg/mg, and baseline eGFR within 10 ml/min per 1.73 m(2)), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression. RESULTS: Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio. CONCLUSIONS: Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function.