Stroke Rehabilitation in Low- and Middle-Income Countries: Challenges and Opportunities.

ABSTRACT: Stroke remains the second leading cause of global disability with 87% of stroke-related disability occurring in low- and middle-income countries. In low- and middle-income countries, access to acute stroke interventions is often limited, making effective poststroke rehabilitation potentially the best available intervention to promote poststroke recovery. Here, we build on our experience as an illustrative example of barriers individuals with stroke face in accessing rehabilitation services and review the literature to summarize challenges to providing effective rehabilitation in low- and middle-income countries. First, we focus on barriers individuals with stroke face in accessing rehabilitation in low- and middle-income countries, including health system barriers, such as lack of national guidelines, low prioritization of rehabilitation services, and inadequate numbers of skilled rehabilitation specialists, as well as patient factors, including limited health literacy, financial constraints, and transportation limitations. Next, we highlight consequences of this lack of rehabilitation access, including higher mortality, poorer functional outcomes, financial burden, caregiver stress, and loss of gross domestic product at a national level. Finally, we review possible strategies that could improve access and quality of rehabilitation services in low- and middle-income countries, including creation of inpatient stroke units, increased training opportunities for rehabilitation specialists, task shifting to available healthcare workers or caregivers, telerehabilitation, and community-based rehabilitation services.

Biological Sex Differences in Risk Factors and Outcomes Among Hospitalized Adults With Stroke in Lusaka, Zambia.

OBJECTIVE: We investigated sex differences in clinical characteristics and outcomes among hospitalized adults with stroke in Zambia. METHODS: We retrospectively collected information for 324 consecutively hospitalized adults with stroke on the neurology service at the University Teaching Hospital in Lusaka, Zambia, between October 2018 and March 2019. Stroke characteristics were then compared by biological sex. RESULTS: Female participants constituted 62% (n = 200) of the cohort, were older (61 ± 19 vs 57 ± 16 years, p = 0.06), had fewer hemorrhagic stroke than male participants (22% vs 37%, p = 0.001), and had higher rates of hypertension (84% vs 74%, p = 0.04), diabetes (19% vs 13%, p = 0.04), heart disease (38% vs 27%, p = 0.04), and history of stroke (26% vs 14%, p = 0.01). Male participants had higher rates of alcohol (33% vs 4%, p < 0.001) and tobacco (19% vs 2%, p < 0.001) use. Female participants were less likely to have neuroimaging completed during their hospitalization (82% vs 94%, p = 0.002) and had higher 90 days postdischarge mortality (28% vs 10%, p = 0.002) independent of age and stroke subtype (OR 2.48, 95% CI 1.1-5.58, p = 0.03). DISCUSSION: Female participants in this Zambian stroke cohort had a higher prevalence of vascular risk factors but were less likely to have neuroimaging completed. Postdischarge mortality was markedly higher among female participants even after adjusting for age and stroke subtype. Our data highlight the need for future studies of social and socioeconomic factors that may influence stroke-related outcomes.

Predictors of in-hospital and 90-day post-discharge stroke mortality in Lusaka, Zambia.

BACKGROUND: Factors associated with stroke mortality are understudied in sub-Saharan Africa but have implications for designing interventions that improve stroke outcomes. We investigated predictors of in-hospital and 90-day post-discharge stroke mortality in Lusaka, Zambia. METHODS: Data from consecutive adults admitted with stroke at University Teaching Hospital in Lusaka, Zambia between October 2018 and March 2019 were retrospectively reviewed for clinical in-hospital outcomes. Vital status at 90-days post-discharge was determined through phone calls. Factors associated with stroke mortality were included in multivariable logistic regression models utilizing multiple imputation analysis to determine independent predictors of in-hospital and 90-days post-discharge mortality. RESULTS: In-hospital mortality was 24%, and 90-day post-discharge mortality was 22% among those who survived hospitalization. Hemorrhagic and unknown strokes, ICU care, seizures, and aspiration pneumonia were significantly associated with in-hospital mortality. Among these, hemorrhagic stroke (OR 2.88, 95% CI 1.27-6.53, p = 0.01) and seizures (OR 29.5, 95% CI 2.14-406, p = 0.01) remained independent predictors of in-hospital mortality in multivariable analyses. Ninety-day post-discharge mortality was significantly associated with older age, previous stroke, atrial fibrillation, and aspiration pneumonia, but only older age (OR 1.04, 95% CI 1.01-1.06, p = 0.007) and aspiration pneumonia (OR 3.93, 95% CI 1.30-11.88, p = 0.02) remained independently associated with 90-day mortality in multivariable analyses. CONCLUSION: This Zambian stroke cohort had high in-hospital and 90-day post-discharge mortality that were associated with several in-hospital complications. Our data indicate the need for improvement in both acute stroke care and post-stroke systems of care to improve stroke outcomes in Zambia.

Stimulation of Dopamine Production by Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive.

BACKGROUND: Parkinson's disease (PD) is one of the most important neurodegenerative disorders in human in which recovery of functions could be achieved by improving the survival and function of residual dopaminergic neurons in the substantia nigra pars compacta. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the dopamine (DA) biosynthesis pathway. OBJECTIVE: Earlier our laboratory has shown that sodium benzoate (NaB), a metabolite of cinnamon and an FDA-approved drug against urea cycle disorders and glycine encephalopathy, increases neuroprotective molecules and protects dopaminergic neurons in a mouse model of PD. Here, we examined whether NaB could stimulate the production of DA in dopaminergic neurons. METHODS: We employed PCR, real-time PCR, western blot, immunostaining, and HPLC to study the signature function of dopaminergic neurons. Locomotor functions were monitored in mice by open-field. RESULTS: NaB increased the mRNA and protein expression of TH to produce DA in mouse MN9D dopaminergic neuronal cells. Accordingly, oral feeding of NaB increased the expression of TH in the nigra, upregulated striatal DA, and improved locomotor activities in striatum of normal C57/BL6 and aged A53T-α-syn transgenic mice. Rapid induction of cAMP response element binding (CREB) activation by NaB in dopaminergic neuronal cells and the abrogation of NaB-induced expression of TH by siRNA knockdown of CREB suggest that NaB stimulates the transcription of TH in dopaminergic neurons via CREB. CONCLUSION: These results indicate a new function of NaB in which it may be beneficial in PD via stimulation of DA production from residual dopaminergic neurons.

Risk factors and outcomes of HIV-associated stroke in Zambia.

OBJECTIVE: To compare risk factors and clinical outcomes between people with HIV (PWH) and HIV-uninfected (HIV-) adults with stroke hospitalized in Zambia. METHODS: We retrospectively reviewed charts of all adults admitted to the University Teaching Hospital in Lusaka, Zambia with a clinical diagnosis of stroke between October 2018 and March 2019. Standardized data collection instruments were used to collect demographic, clinical, laboratory and imaging results. Comparison between individuals with and without HIV infection was made using t tests for continuous parametric variables, Wilcoxon rank-sum tests for continuous nonparametric variables, and chi-square analyses for categorical variables. RESULTS: Two hundred and seventy-two adults with stroke were admitted of whom 58 (21%) were PWH. Compared with HIV- participants, PWH were younger [(48 ±â€Š14) years versus 62 ±â€Š18) years, P < 0.001]. PWH were less likely to have hypertension (65 versus 83%, P = 0.003) and more likely to have no traditional cerebrovascular risk factors (34 versus 15%, P = 0.01). Deep vein thrombosis (DVT) (4 versus 1%, P = 0.04) was more common during hospitalization amongst PWH but there was no difference in in-hospital mortality (21 versus 23%, P = 0.65). Among PWH with stroke, factors associated with in-hospital mortality were Glasgow Coma Scale (GCS) on admission (7 versus 10, P = 0.046), hypertension (92 versus 59%, P = 0.04) and fever (58 versus 13%, P = 0.003). CONCLUSION: This Zambian cohort of PWH and stroke is notable for being significantly younger with fewer traditional stroke risk factors but higher rates of DVT than their HIV-uninfected counterparts. GCS on admission, hypertension and fever were associated with in-hospital mortality.

Training in Neurology: Implementation and Evaluation of an Objective Structured Clinical-Examination Tool for Neurology Postgraduate Trainees in Lusaka, Zambia.

BACKGROUND: We established Zambia's first neurology residency program at the University of Zambia School of Medicine and the University Teaching Hospital in Lusaka. OBJECTIVE: To evaluate the feasibility and effectiveness of a modified objective structured clinical examination (OSCE) to assess clinical skills. METHODS: The neurology training program's 3 participants completed the OSCE exercise in February 2019. We used smartphones to videotape trainees performing a physical examination and oral presentation in the neurology clinic. Trainees and faculty reviewed the videos independently using a standardized rubric and then met for in-person feedback. RESULTS: Three trainees completed pre- and post-OSCE surveys rating their confidence in elements of the history and examination. Trainees' average self-confidence scores improved from the pre- to post-OSCE survey in every category (pre-OSCE: mean score 6.84, range 4.8-7.8, SD 0.92; post-OSCE: mean score 7.9, range 5.67-9.33, SD 0.86). Qualitative feedback showed trainees found the OSCE helpful, routinely applied feedback, and would appreciate repeating OSCEs. CONCLUSIONS: OSCEs improve trainees' self-confidence and can be modified and successfully implemented in a resource-limited neurology postgraduate training program. Important OSCE modifications involved using smartphones for videotaping and a real patient encounter rather than a standardized patient. Embedding the experience within a busy clinic day was practical, applicable, and efficient. Future work should expand use of OSCEs both within the Zambian neurology residency program and non-neurology training programs. Including additional video reviewers could add to the validity of clinical skills assessment. Videos could also be used for remote mentorship and teaching purposes.

Risk factors and outcomes of hospitalized stroke patients in Lusaka, Zambia.

BACKGROUND: Limited data exists about stroke risk factors and outcomes in sub-Saharan African countries, including Zambia. We aim to fill this gap by describing features of hospitalized stroke patients at University Teaching Hospital (UTH), the national referral hospital in Lusaka, Zambia. METHODS: We conducted a retrospective study of consecutive adults with stroke admitted to UTH's inpatient neurology service from October 2018 to March 2019. Strokes were classified as ischemic or hemorrhagic based on CT scan results and unknown if CT scan was not obtained. Chi-square analyses and t-tests were used to compare characteristics between cohorts with differing stroke subtypes. RESULTS: Adults with stroke constituted 43% (n = 324) of all neurological admissions, had an average age of 60 ± 18 years, and 62% of the cohort was female. Stroke subtypes were 58% ischemic, 28% hemorrhagic, and 14% unknown. Hypertension was present in 80% of all strokes and was significantly associated with hemorrhagic stroke (p = 0.03). HIV was present in 18% of all strokes and did not significantly differ by stroke subtype. Diabetes (16%), heart disease (34%), atrial fibrillation (9%), and past medical history of stroke (22%) were all significantly more common in patients with ischemic stroke (p < 0.05). In-hospital mortality was 24% overall and highest among individuals with hemorrhagic strokes (33%, p = 0.005). CONCLUSIONS: This Zambian stroke cohort is notable for its young age, significant HIV burden, high in-hospital mortality, and high rates of uncontrolled hypertension. Our results demonstrate Zambia's substantial stroke burden, significant contribution of HIV to stroke, and the need to improve primary stroke prevention.

Aspiration Pneumonia in Adults Hospitalized With Stroke at a Large Academic Hospital in Zambia.

BACKGROUND AND OBJECTIVES: Preventing complications of stroke such as poststroke aspiration pneumonia (PSAP) may improve stroke outcomes in resource-limited settings. We investigated the incidence and associated mortality of PSAP in Zambia. METHODS: We conducted a prospective cohort study of adults with stroke at University Teaching Hospital (Lusaka, Zambia) between December 2019 and March 2020. NIH Stroke Scale, Glasgow Coma Scale, and Modified Rankin Scale scores and 9 indicators of possible PSAP were collected serially over each participant's admission. PSAP was defined as ≥4 indicators present, and possible PSAP as 2%-3% present. T tests and χ2 tests were used to compare clinical parameters across PSAP groups. Logistic regression was used to assess the relative effects of age, sex, PSAP status, and initial stroke severity on inpatient mortality. RESULTS: We enrolled 125 participants. Mean age was 60 ± 16 years, 61% were female, 55% of strokes were ischemic, and the baseline NIH Stroke Scale score was 19.7 ± 8.7. Thirty-eight (30%) had PSAP, and 32 (26%) had possible PSAP. PSAP was associated with older age and more adverse stroke severity scores. Fifty-nine percent of participants with PSAP died compared with 39% with possible PSAP and 8% with no PSAP. PSAP status independently predicted inpatient mortality after controlling for age, sex, and initial stroke severity. Swallow screening was not performed for any participant. DISCUSSION: PSAP is common and life threatening in Zambia, especially among older participants with severe stroke presentations. PSAP was associated with significantly increased mortality independent of initial stroke severity, suggesting that interventions to mitigate PSAP may improve stroke outcomes in Zambia and other resource-limited settings.

Using phylogenetic and coalescent methods to understand the species diversity in the Cladia aggregata complex (Ascomycota, Lecanorales).

The Cladia aggregata complex is one of the phenotypically most variable groups in lichenized fungi, making species determination difficult and resulting in different classifications accepting between one to eight species. Multi-locus DNA sequence data provide an avenue to test species delimitation scenarios using genealogical and coalescent methods, employing gene and species trees. Here we tested species delimitation in the complex using molecular data of four loci (nuITS and IGS rDNA, protein-coding GAPDH and Mcm-7), including 474 newly generated sequences. Using a combination of ML and Bayesian gene tree topologies, species tree inferences, coalescent-based species delimitation, and examination of phenotypic variation we assessed the circumscription of lineages. We propose that results from our analyses support a 12 species delimitation scenario, suggesting that there is a high level of species diversity in the complex. Morphological and chemical characters often do not characterize lineages but show some degree of plasticity within at least some of the clades. However, clades can often be characterized by a combination of several phenotypical characters. In contrast to the amount of homoplasy in the morphological characters, the data set exhibits some geographical patterns with putative species having distribution patterns, such as austral, Australasian or being endemic to Australia, New Zealand or Tasmania.