Prevalence and Risk Factors of Distal Symmetric Polyneuropathy Among Predominantly Non-Hispanic Black, Low-Income Patients.

BACKGROUND AND OBJECTIVES: Distal symmetric polyneuropathy (DSP) is a disabling, often painful condition associated with falls and reduced quality of life. Non-Hispanic Black people and people with low income are underrepresented in existing DSP studies; therefore, it is unknown whether data accurately reflect the prevalence, risk factors, and burden of disease in these populations. METHODS: Patients older than 40 years presenting to an outpatient internal medicine clinic predominantly serving Medicaid patients in Flint, Michigan, were enrolled in a cross-sectional study. Demographics, clinical characteristics, including medication use, anthropomorphic measurements, fasting lipids, and hemoglobin A1c were collected. DSP was defined using the modified Toronto Clinical Neuropathy Score (mTCNS). Multivariable logistic regression was performed to model DSP and undiagnosed DSP as a function of potential risk factors age, metabolic syndrome, and race. DSP burden was measured using Peripheral Neuropathy Quality of Life Instrument-97. RESULTS: Two hundred participants were enrolled, and 169 (85%) completed all data collection. The population was 55% female of mean age (SD) 58.2 years (10.4) and 69% non-Hispanic Black. Among the population, 50% had diabetes, 67% had metabolic syndrome, and 47% had a household income <$20,000. DSP was present in 73% of the population, of which 75% were previously undiagnosed. Neuropathic pain was documented in 57% of participants with DSP. DSP based on mTCNS criteria was associated with older age (odds ratio [OR] 1.1 [95% confidence interval (CI) 1.03-1.2]) and metabolic syndrome (OR 4.4 [1.1-18.1]). Non-Hispanic Black participants had lower odds of DSP (OR 0.1 [0.01-0.4]) than non-Hispanic White and Hispanic participants. DSP burden was high, including increased pain, health-related worry, and poorer quality of life (all p < 0.001). DISCUSSION: DSP is extremely common and often underrecognized in this predominantly non-Hispanic Black, low-income population and leads to substantial disease burden. Metabolic syndrome is a highly prevalent, modifiable risk factor in this population that should be managed to lower DSP prevalence.

Recognizing Myopathy in Patients with Muscle Weakness or Pain.

Muscle weakness and pain can be seen in orthopedic, rheumatologic, cardiac, and musculoskeletal conditions in addition to neurologic disorders. Myopathy, which describes a heterogenous group of hereditary and acquired disorders that affect muscle channels, structure, and metabolism, is one possible cause. This review focuses on essential information to support primary care providers as they assess patients with muscle weakness and pain for myopathy. As with most neurologic disorders, a thorough clinical history and physical examination are essential first steps. These findings will then guide diagnostic testing and facilitate appropriate management or referral for further neuromuscular care.

Early Initiation of Antiretroviral Therapy is Protective Against Seizures in Children With HIV in Zambia: A Prospective Case-Control Study.

BACKGROUND: Seizures are relatively common among children with HIV in low- and middle-income countries and are associated with significant morbidity and mortality. Early treatment with antiretroviral therapy (ART) may reduce this risk by decreasing rates of central nervous system infections and HIV encephalopathy. METHODS: We conducted a prospective, unmatched case-control study. We enrolled children with new-onset seizure from University Teaching Hospital in Lusaka, Zambia and 2 regional hospitals in rural Zambia. Controls were children with HIV and no history of seizures. Recruitment took place from 2016 to 2019. Early treatment was defined as initiation of ART before 12 months of age, at a CD4 percentage >15% in children aged 12-60 months or a CD4 count >350 cells/mm 3 for children aged 60 months or older. Logistic regression models were used to evaluate the association between potential risk factors and seizures. RESULTS: We identified 73 children with new-onset seizure and compared them with 254 control children with HIV but no seizures. Early treatment with ART was associated with a significant reduction in the odds of seizures [odds ratio (OR) 0.04, 95% confidence interval: 0.02 to 0.09; P < 0.001]. Having an undetectable viral load at the time of enrollment was strongly protective against seizures (OR 0.03, P < 0.001), whereas history of World Health Organization Stage 4 disease (OR 2.2, P = 0.05) or CD4 count <200 cells/mm 3 (OR 3.6, P < 0.001) increased risk of seizures. CONCLUSIONS: Early initiation of ART and successful viral suppression would likely reduce much of the excess seizure burden in children with HIV.

Diabetic Neuropathies.

OBJECTIVE: This article provides an up-to-date review of the diagnosis and management of the most common neuropathies that occur in patients with diabetes. LATEST DEVELOPMENTS: The prevalence of diabetes continues to grow worldwide and, as a result, the burden of diabetic neuropathies is also increasing. Most diabetic neuropathies are caused by hyperglycemic effects on small and large fiber nerves, and glycemic control in individuals with type 1 diabetes reduces neuropathy prevalence. However, among people with type 2 diabetes, additional factors, particularly metabolic syndrome components, play a role and should be addressed. Although length-dependent distal symmetric polyneuropathy is the most common form of neuropathy, autonomic syndromes, particularly cardiovascular autonomic neuropathy, are associated with increased mortality, whereas lumbosacral radiculoplexus neuropathy and treatment-induced neuropathy cause substantial morbidity. Recent evidence-based guidelines have updated the recommended treatment options to manage pain associated with distal symmetric polyneuropathy of diabetes. ESSENTIAL POINTS: Identifying and appropriately diagnosing the neuropathies of diabetes is key to preventing progression. Until better disease-modifying therapies are identified, management remains focused on diabetes and metabolic risk factor control and pain management.

The effect of surgical weight loss on diabetes complications in individuals with class II/III obesity.

AIMS/HYPOTHESIS: The aim of this study was to determine the effect of bariatric surgery on diabetes complications in individuals with class II/III obesity (BMI > 35 kg/m2). METHODS: We performed a prospective cohort study of participants with obesity who underwent bariatric surgery. At baseline and 2 years following surgery, participants underwent metabolic phenotyping and diabetes complication assessments. The primary outcomes for peripheral neuropathy (PN) were a change in intra-epidermal nerve fibre density (IENFD, units = fibres/mm) at the distal leg and proximal thigh, the primary outcome for cardiovascular autonomic neuropathy (CAN) was a change in the expiration/inspiration (E/I) ratio, and the primary outcome for retinopathy was a change in the mean deviation on frequency doubling technology testing. RESULTS: Among 127 baseline participants, 79 completed in-person follow-up (age 46.0 ± 11.3 years [mean ± SD], 73.4% female). Participants lost a mean of 31.0 kg (SD 18.4), and all metabolic risk factors improved except for BP and total cholesterol. Following bariatric surgery, one of the primary PN outcomes improved (IENFD proximal thigh, +3.4 ± 7.8, p<0.01), and CAN (E/I ratio -0.01 ± 0.1, p=0.89) and retinopathy (deviation -0.2 ± 3.0, p=0.52) were stable. Linear regression revealed that a greater reduction in fasting glucose was associated with improvements in retinopathy (mean deviation point estimate -0.7, 95% CI -1.3, -0.1). CONCLUSIONS/INTERPRETATION: Bariatric surgery may be an effective approach to reverse PN in individuals with obesity. The observed stability of CAN and retinopathy may be an improvement compared with the natural progression of these conditions; however, controlled trials are needed.

Patient and health care provider knowledge of diabetes and diabetic microvascular complications: a comprehensive literature review.

Diabetic retinopathy, neuropathy, and nephropathy occur in more than 50% of people with diabetes, contributing substantially to morbidity and mortality. Patient understanding of these microvascular complications is essential to ensure early recognition and treatment of these sequalae as well as associated symptoms, yet little is known about patient knowledge of microvascular sequalae. In this comprehensive literature review, we provide an overview of existing knowledge regarding patient knowledge of diabetes, retinopathy, neuropathy, and nephropathy. We also discuss health care provider's knowledge of these sequalae given that patients and providers must work together to achieve optimal care. We evaluated 281 articles on patient and provider knowledge of diabetic retinopathy, neuropathy, and nephropathy as well as predictors of improved knowledge and screening practices. Results demonstrated that patient and provider knowledge of microvascular sequalae varied widely between studies, which may reflect sociocultural or methodologic differences. Knowledge assessment instruments varied between studies with limited validation data and few studies controlled for confounding. Generally, improved patient knowledge was associated with greater formal education, longer diabetes duration, and higher socioeconomic status. Fewer studies examined provider knowledge of sequalae, yet these studies identified multiple misconceptions regarding appropriate screening practices for microvascular complications and the need to screen patients who are asymptomatic. Further investigations are needed that use well validated measures, control for confounding, and include diverse populations. Such studies will allow identification of patients and providers who would benefit from interventions to improve knowledge of microvascular complications and, ultimately, improve patient outcomes.

Towards prevention of diabetic peripheral neuropathy: clinical presentation, pathogenesis, and new treatments.

Diabetic peripheral neuropathy (DPN) occurs in up to half of individuals with type 1 or type 2 diabetes. DPN results from the distal-to-proximal loss of peripheral nerve function, leading to physical disability and sometimes pain, with the consequent lowering of quality of life. Early diagnosis improves clinical outcomes, but many patients still develop neuropathy. Hyperglycaemia is a risk factor and glycaemic control prevents DPN development in type 1 diabetes. However, glycaemic control has modest or no benefit in individuals with type 2 diabetes, probably because they usually have comorbidities. Among them, the metabolic syndrome is a major risk factor for DPN. The pathophysiology of DPN is complex, but mechanisms converge on a unifying theme of bioenergetic failure in the peripheral nerves due to their unique anatomy. Current clinical management focuses on controlling diabetes, the metabolic syndrome, and pain, but remains suboptimal for most patients. Thus, research is ongoing to improve early diagnosis and prognosis, to identify molecular mechanisms that could lead to therapeutic targets, and to investigate lifestyle interventions to improve clinical outcomes.

Cardiac Involvement and Arrhythmias Associated with Myotonic Dystrophy.

Myotonic dystrophy is an autosomal dominant genetic disease of nucleotide expansion resulting in neuromuscular disease with two distinct subtypes. There are significant systemic manifestations of this condition including progressive muscular decline, neurologic abnormalities, and cardiac disease. Given the higher prevalence of cardiac dysfunction compared to the general population, there is significant interest in early diagnosis and prevention of cardiac morbidity and mortality. Cardiac dysfunction has an origin in abnormal and unstable nucleotide repeats in the DMPK and CNBP genes which have downstream effects leading to an increased propensity for arrhythmias and left ventricular systolic dysfunction. Current screening paradigms involve the use of routine screening electrocardiograms, ambulatory electrocardiographic monitors, and cardiac imaging to stratify risk and suggest further invasive evaluation. The most common cardiac abnormality is atrial arrhythmia, however there is significant mortality in this population from high-degree atrioventricular block and ventricular arrhythmia. In this review, we describe the cardiac manifestations of myotonic dystrophy with an emphasis on arrhythmia which is the second most common cause of death in this population after respiratory failure.

A qualitative study of factors resulting in care delays for adults with meningitis in Zambia.

BACKGROUND: Meningitis causes significant mortality in regions with high comorbid HIV and TB. Improved outcomes are hindered by limited understanding of factors that delay adequate care. METHODS: In-depth interviews of patients admitted to the University Teaching Hospital with suspected meningitis, their caregivers, doctors and nurses were conducted. Patient/caregiver interviews explored meningitis understanding, treatment prior to admission and experiences since admission. Provider interviews addressed current and prior experiences with meningitis patients and hospital barriers to care. A conceptual framework based on the Three Delays Model identified factors that delayed care. RESULTS: Twenty-six patient/caregiver, eight doctor and eight nurse interviews occurred. Four delays were identified: in-home care; transportation to a health facility; clinic/first-level hospital care; and third-level hospital. Overcrowding and costly diagnostic testing delayed outpatient care; 23% of patients began with treatment inside the home due to prior negative experiences with biomedical care. Admission occurred after multiple clinic visits, where subsequent delays occurred during testing and treatment. CONCLUSIONS: Delays in care from home to hospital impair quality meningitis care in Zambia. Interventions to improve outcomes must address patient, community and health systems factors. Patient/caregiver education regarding signs of meningitis and indications for care-seeking are warranted to reduce treatment delays.

Clinical characteristics and outcomes after new-onset seizure among Zambian children with HIV during the antiretroviral therapy era.

OBJECTIVE: This study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new-onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30-day mortality and cause of death are also reported. METHODS: Children living with HIV (CLWHIV) with new-onset seizures were prospectively evaluated at one large urban teaching hospital and two non-urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients' care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed. RESULTS: From April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2-10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non-accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty-two (30%) children died within 30 days of the index seizure. SIGNIFICANCE: Despite widespread ART roll out in Zambia, new-onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.

A qualitative study of patient, caregiver, doctor and nurse views of factors influencing lumbar puncture uptake in Zambia.

BACKGROUND: Uptake of lumbar puncture (LP) remains low in regions with a high prevalence of central nervous system (CNS) infections like Zambia. Efforts to improve uptake are hindered by limited understanding of factors influencing LP uptake. METHODS: Semistructured qualitative interviews were conducted with patients with suspected CNS infection, caregivers, doctors and nurses at the University Teaching Hospitals in 2016. Questions focused on LP experiences, knowledge, the consent process and health system barriers to LP among patients with an LP indication. Interviews were transcribed, translated to English and analysed using a thematic approach. RESULTS: We recruited 24 adult patients, 36 caregivers of adult patients, 63 caregivers of paediatric patients, 20 doctors and 30 nurses (173 in total). LP barriers arose from both patients/caregivers and health providers and included community apprehension about LP, proxy (family) consensus consent practices, competing clinical demands, wariness of patient/caregiver responses, limitations in consumables and time to complete the LP. This could result in consent not being obtained correctly. LP enablers included patient/caregiver perceived LP utility, provider comfort with LP and in-person counselling. CONCLUSIONS: LP uptake is a complex sociocultural process influenced by patient, healthcare and community-level factors. Interventions to improve uptake must address multiple barriers to be successful.

Lumbar Puncture-Related Knowledge, Attitudes, and Practices among Patients, Caregivers, Doctors, and Nurses in Zambia.

Lumbar puncture (LP) is underused for neuroinfectious disease diagnosis in Zambia, but reasons for poor uptake remain speculative. This cross-sectional study assessed LP knowledge, attitudes, and practices among patients/caregivers and healthcare workers (HCWs) and predictors of LP completion. Patients with suspected central nervous system infection, caregivers, and HCWs at the University Teaching Hospitals in 2016 were eligible. Questions adapted from the existing literature were used for a LP knowledge score. Predictors of knowledge scores were assessed independently for patients/caregivers and HCWs. Predictors of LP completion were assessed using multivariable logistic regression. Among 123 patients/caregivers, LP knowledge was poor. Pediatric caregivers were more likely than adult patients/caregivers to report LP could be replaced by neuroimaging (90% versus 78%, P < 0.001) and cause paralysis (57% versus 39%, P = 0.01). There were no significant predictors of the knowledge score among patients/caregivers. Among HCWs, 28% said LP makes patients clinically worse, and 60% reported it could cause paralysis. The increased knowledge score was associated with greater wealth (P = 0.03) and personally knowing someone who underwent LP (P < 0.001). Lumbar puncture was completed on 67/112 (57%) patients and was associated with an increased knowledge score (OR: 1.62 [95% CI: 1.19-2.23]). Pediatric patients (OR: 0.18 [95% CI: 0.07-0.47]) and those with a fear of paralysis (OR 0.29 [95% CI: 0.11-0.77]) were less likely to undergo LP. Improving LP-related knowledge may improve uptake. Healthcare workers sense of LP risk may also play a role in encouraging/discouraging use.

Challenges and opportunities in examining and addressing intersectional stigma and health.

BACKGROUND: 'Intersectional stigma' is a concept that has emerged to characterize the convergence of multiple stigmatized identities within a person or group, and to address their joint effects on health and wellbeing. While enquiry into the intersections of race, class, and gender serves as the historical and theoretical basis for intersectional stigma, there is little consensus on how best to characterize and analyze intersectional stigma, or on how to design interventions to address this complex phenomenon. The purpose of this paper is to highlight existing intersectional stigma literature, identify gaps in our methods for studying and addressing intersectional stigma, provide examples illustrating promising analytical approaches, and elucidate priorities for future health research. DISCUSSION: Evidence from the existing scientific literature, as well as the examples presented here, suggest that people in diverse settings experience intersecting forms of stigma that influence their mental and physical health and corresponding health behaviors. As different stigmas are often correlated and interrelated, the health impact of intersectional stigma is complex, generating a broad range of vulnerabilities and risks. Qualitative, quantitative, and mixed methods approaches are required to reduce the significant knowledge gaps that remain in our understanding of intersectional stigma, shared identity, and their effects on health. CONCLUSIONS: Stigmatized identities, while often analyzed in isolation, do not exist in a vacuum. Intersecting forms of stigma are a common reality, yet they remain poorly understood. The development of instruments and methods to better characterize the mechanisms and effects of intersectional stigma in relation to various health conditions around the globe is vital. Only then will healthcare providers, public health officials, and advocates be able to design health interventions that capitalize on the positive aspects of shared identity, while reducing the burden of stigma.

A scoping review of health-related stigma outcomes for high-burden diseases in low- and middle-income countries.

BACKGROUND: Stigma is associated with health conditions that drive disease burden in low- and middle-income countries (LMICs), including HIV, tuberculosis, mental health problems, epilepsy, and substance use disorders. However, the literature discussing the relationship between stigma and health outcomes is largely fragmented within disease-specific siloes, thus limiting the identification of common moderators or mechanisms through which stigma potentiates adverse health outcomes as well as the development of broadly relevant stigma mitigation interventions. METHODS: We conducted a scoping review to provide a critical overview of the breadth of research on stigma for each of the five aforementioned conditions in LMICs, including their methodological strengths and limitations. RESULTS: Across the range of diseases and disorders studied, stigma is associated with poor health outcomes, including help- and treatment-seeking behaviors. Common methodological limitations include a lack of prospective studies, non-representative samples resulting in limited generalizability, and a dearth of data on mediators and moderators of the relationship between stigma and health outcomes. CONCLUSIONS: Implementing effective stigma mitigation interventions at scale necessitates transdisciplinary longitudinal studies that examine how stigma potentiates the risk for adverse outcomes for high-burden health conditions in community-based samples in LMICs.

Mortality & recurrent seizure risk after new-onset seizure in HIV-positive Zambian adults.

BACKGROUND: Recurrent seizure risks in HIV-positive people with new-onset seizure are largely unknown, making it challenging to offer optimal recommendations regarding antiepileptic drug (AED) initiation. Existing outcomes data is limited, and risk factor identification requires a diagnostic assessment, which is often unavailable in regions heavily effected by HIV, like sub-Saharan Africa. METHODS: HIV-positive Zambian adults with new-onset seizure were enrolled in a prospective cohort study to determine seizure recurrence and risk factors for recurrence. Seizure etiology was evaluated, and recurrent seizures and medication usage were assessed during clinic visits. Due to unexpectedly high mortality rates, predictors of death were evaluated using proportional hazards with Gray's test to compare cumulative incidence functions for recurrent seizure across groups adjusting for the competing outcome of death. RESULTS: 95 patients were enrolled (mean age 37 years, 43% female, 83% with Karnofsky > 50) and followed for a mean of 293 days (median 241 (IQR: 29-532)). At presentation, 50 (53%) were in status epilepticus. The majority (91, 85%) had advanced HIV disease and 65 (68%) were not on combined antiretroviral therapy (cART). After extensive workup, seizure etiology remained unknown in 16 (17%). Average time to cART initiation after enrollment was 61 days. During follow up, 37 (39%) died and 23 (24%) had recurrent seizure. Most deaths (25/37, 68%) occurred in the first 60 days post-index seizure. Individuals with advanced HIV were more likely to die (HR: 19.1 [95% CI: 1.1-333.4]) as were those whose seizure etiology remained unknown (HR: 2.2 [95% CI: 1.1-4.4]). Among participants that survived from enrolment to the end of data collection on 10 May 2013 (n = 58), 20 (34%) experienced recurrent seizures. CONCLUSIONS: New-onset seizure among HIV-positive Zambian adults is associated with high mortality despite good functional status prior to presentation. Advanced HIV infection and failure to identify an underlying seizure etiology are associated with greater mortality. Recurrent seizures occur in over a third of survivors within only 2 years of follow-up. This provides evidence to support AED initiation after first seizure in HIV-positive individuals with advanced HIV disease at the time of presentation though the risks of AED-cART interactions remain a concern and warrant further study.

Evaluating layered stigma from comorbid HIV and epilepsy among Zambian adults.

BACKGROUND AND PURPOSE: Stigma hinders care for patients with neurologic illness. Layered stigma due to comorbid disease is common yet poorly characterized due to lack of instruments. Epilepsy and HIV are prototypical stigmatized conditions widespread in sub-Saharan Africa. METHODS: We assessed layered stigma among people with HIV and epilepsy (n = 21), epilepsy only (n = 88), and HIV only (n = 40) in Zambia. Epilepsy-associated stigma was assessed using the Stigma Scale of Epilepsy and Jacoby's Stigma Scale. HIV-related stigma was assessed using the HIV/AIDS Stigma Instrument-People Living with HIV/AIDS and Jacoby's Stigma Scale. Stigma was compared across groups using χ 2 tests. RESULTS: 55% (60/109) with epilepsy reported some epilepsy-associated stigma and 20% (12/61) with HIV reported HIV self-stigmatization. Those with HIV and epilepsy were more likely to associate seizures with fear (OR 6.1 [95% CI: 1.3-27.9]) and epilepsy with dependence (OR 4.6 [1.1-19.6]), controlling for age, gender, marital status, and employment. Those with comorbid disease were more likely to report they were "no longer a person" and felt "blamed" for their HIV. Controlling for age and gender, the difference in depersonalization remained (OR: 6.4 [1.1-36.1]). CONCLUSION: Individuals carrying the burden of one stigmatized condition may be more vulnerable to stigma from a comorbid disease.