Depression following small vessel stroke is common and more prevalent in women.

OBJECTIVES: We sought to examine the frequency of depression after small vessel-type stroke (SVS) and associated risk factors. MATERIALS AND METHODS: We conducted a retrospective analysis of a prospective cohort of patients enrolled in the American Stroke Association-Bugher SVS Study, which included 200 participants within 2-years of SVS and 79 controls without a history of stroke from 2007 to 2012 at four sites. The primary outcome was PHQ-8, with scores ≥10 consistent with post-stroke depression (PSD). A logistic regression adjusted for age, race, sex, history of diabetes and Short-Form Montreal Cognitive Assessment score (SF-MoCA) was used to compare the risk of having depression after SVS compared to controls. Another logistic regression, adjusted for age, sex, race, level of education, SF-MoCA, white matter disease (WMD) burden, stroke severity (NIHSS), time between stroke and depression screen, history of diabetes, and history of hypertension was used to identify factors independently associated with depression in participants with SVS. RESULTS: The cohort included 161 participants with SVS (39 excluded due to missing data) and 79 controls. The mean interval between stroke and depression screening was 74 days. Among participants with SVS, 31.7% (n = 51) had PSD compared to 6.3% (n = 5) of controls (RR = 5.44, 95% CI = 2.21-13.38, p = 0.0002). The only two variables independently associated with PSD in participants with SVS were female sex (RR = 1.84, 95% CI = 1.09-3.09, p = 0.020) and diabetes (RR 1.69, 95% CI 1.03-2.79). CONCLUSIONS: After adjusting for several demographic and clinical variables, having a SVS was associated with an approximate 5-fold increased risk of depression and was more frequent in women and in those with diabetes. The extent of WMD was not independently associated with PSD, suggesting that small vessel disease in the setting of an overt SVS may not account for the increased prevalence of depression.

Epilepsy among the older population of sub-Saharan Africa: Analysis of the global burden of disease database.

INTRODUCTION: Epilepsy is considered one of the most burdensome neurologic diseases by the World Health Organization due to the high risk of morbidity and mortality. Few studies have investigated the epidemiology of idiopathic epilepsy in Sub-Saharan Africa (SSA). This study aims to characterize the disease burden of epilepsy among the older population in SSA via a large international database. METHODS: Descriptive epidemiological data from the Global Burden of Disease (GBD) database was collected for idiopathic epilepsy in all regions of SSA. The "older" population was defined as 55 years of age and above. The variables of interest included mortality, incidence, prevalence, and disability-adjusted life years (DALYs) rates per one hundred thousand populations. RESULTS: The average mortality rate was highest in Western SSA (6.34 per 100,000), and all regions were significantly higher than the global average (p < 0.001). DALYs and incidence rates of idiopathic epilepsy in all regions of SSA were significantly higher than the global averages (p < 0.01). Globally, the older population had a significantly higher mortality rate than the younger population (2.78 vs 1.62, respectively; p < 0.01). The older population had a higher mortality rate than the younger population in each region of SSA (p < 0.01). Conversely, for DALYs, the younger population had a higher disease burden than the older population globally and in each region of SSA (p < 0.01). CONCLUSION: This study is the first to examine the epidemiologic profile of idiopathic epilepsy in the older population in SSA. Our results indicate that, when compared with the global population, older adults in SSA suffer a greater disease burden and mortality. This study reports the immense need for increased resources and awareness regarding epilepsy in the elderly population of Africa.

"Walking the Journey Together": Creating a unique learning module in provider-patient communication for the care of epilepsy in Uganda.

OBJECTIVE: This report documents the creation of a practical communication skills module about epilepsy care, specifically targeted at first-line care providers who treat patients with epilepsy in Uganda. METHODS: Our team conducted semi-structured interviews, utilizing Zoom video conferencing, with Ugandan physicians specializing in epilepsy care. Our interview guide promoted a semi-structured conversational interview that explored aspects related to developing a patient-provider relationship, how epilepsy is described in a culturally appropriate manner, exploration of alternative treatments, the impact of the stigma of epilepsy, and facilitators and barriers to antiepileptic drug treatment adherence. Each interview was then transcribed, and an inductive thematic content analysis approach was utilized to facilitate the development of thematic communication and care subcategories. The resulting PowerPoint presentation included numerous short audio clips of our Ugandan experts suggesting effective ways of communicating with patients and their families. RESULTS: Our interviews with experts yielded valuable results to customize the WHO mhGAP v2.0 training program to be culturally relevant and effective in Uganda. The educational content consisted of topic summaries integrated with audio clips taken directly from our interviews with the Ugandan providers. Six themes emerged that would serve as the outline for the communication module we co-created with our Ugandan colleagues: The six major themes of the module included: (1) Greeting the patient, (2) Getting the story, (3) Traditional healers, (4) Stigma of epilepsy, (5) Explaining epilepsy, and (6) Treatment adherence. CONCLUSIONS: The communications skills teaching module addresses the most critical aspects of communicating with patients and families living with epilepsy. The format of the presentation, which includes the written and spoken words of experts in epilepsy care, provides a practical approach to the provider-patient interaction, and confronts the stigma associated with this disease. This formatting highlights an effective way for international groups to co-create content in a culturally effective manner.

Evaluation of a tailored epilepsy training program for healthcare providers in Uganda.

OBJECTIVE: This study evaluated an epilepsy training program for healthcare workers that was designed to improve their knowledge of epilepsy, its treatment, and its psychosocial effects. METHODS: This single group, before and after survey was conducted in three regional referral hospitals in Uganda. Healthcare workers participated in a 3-day epilepsy training program and were assessed immediately prior to and following the program using a 39-item epilepsy knowledge questionnaire. Pretest to posttest changes and acceptability ratings were analyzed. RESULTS: Twenty healthcare workers from each of our three study hospitals (N = 60) participated in the study. The average age of the participants was 39.9 years (SD = 9.6). Female participants constituted 45% of the study population. There was a significant improvement in the knowledge of healthcare workers about epilepsy following the training (t = 7.15, p < 0.001). Improvement was seen across the three sub-scores of general knowledge about epilepsy, assessment and diagnosis of epilepsy, and management of epilepsy. Subgroup analysis showed that both high and low baseline scorers showed significant training gains. CONCLUSIONS: The study suggested that our training program was effective in improving the knowledge of health workers about epilepsy and that participants had favorable impressions of the program. Further work is needed to determine if the knowledge is retained over time and if the change in knowledge translates into a change in clinical practice.

Understanding the cultural context of epilepsy care in Uganda: Introduction to this special issue.

This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Validity of the Personal Impact of Epilepsy Scale (PIES) in patients with epilepsy in Uganda.

PURPOSE: We sought to address the construct validity and reliability of the Personal Impact of Epilepsy Scale (PIES), an epilepsy-specific quality-of-life measure, in patients with epilepsy in Uganda. We also sought to assess the applicability of the scale across three languages: English, Luganda, and Runyankole. METHODS: Patients with epilepsy (N = 626) were recruited at the time of care seeking from Mulago National Referral Hospital (MNRH), Butabika National Referral Mental Hospital (BNRMH), and Mbarara Regional Referral Hospital (MRRH), and were given the English, Runyankole, and Luganda versions of the PIES as a part of a larger interview. Reliability, internal consistency specifically, was assessed using three parameters: Cronbach's alpha, McDonald's Omega, and composite reliability. Construct validity (internal structure) was evaluated with principal component analysis (PCA) for three factors, as well as confirmatory factor analysis (CFA) for a three-factor structure of the scale. We also assessed correlations between the three PIES subscales and the seizure severity question in the Liverpool Seizure Severity Scale (LSSS) and reported seizure frequency. RESULTS: The three-factor model of the PIES had adequate reliability, with Cronbach's Alpha, McDonald's Omega, and composite reliability values over 0.7, except for the Cronbach's Alpha and McDonald's Omega values for the second factor, which was slightly lower than 0.7 in the full sample as well as when stratified by study language. The PCA and CFA models for the scale demonstrated adequate fit with the Tucker-Lewis index (TLI), comparative fit index (CFI), and root mean square error of approximation (RMSEA), with TLI and CFI values above 0.9 and RMSEA values less than 0.08. However, the model demonstrated inadequate fit with the Chi-square indicator, which yielded a significant p-value. Individual factor loadings ranged from 0.50 to 0.95 in the full sample, 0.45 to 0.98 in the English sample, and 0.45 to 0.93 in the Luganda sample. Finally, the three PIES subscales aligned with reported seizure frequency and the seizure severity question from the LSSS. CONCLUSIONS: This study presents the first Luganda and Runyankole versions of the PIES, and the first validation of this scale in English and Luganda with patients with epilepsy in Uganda. The PIES was found to have acceptable psychometric properties for reliability and validity parameters. Thus, the scale is recommended for use and for further investigation in patients with epilepsy in Uganda. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Stigma reduction interventions for epilepsy: A systematized literature review.

OBJECTIVE: Epilepsy is a disease that is stigmatized globally. Several studies have introduced sensitization efforts to reduce stigma towards people with epilepsy (PWE) in various settings. Although sensitization efforts have shown some evidence of improved attitudes towards epilepsy, progress has been limited. This systematized literature review summarizes the existing literature concerning interventions that reduce stigma towards PWE. By conducting an overview of existing interventions, we aimed to consolidate knowledge and outcomes of existing efforts as well as highlight gaps and directions for future interventions. METHODS: We searched MEDLINE (via PubMed) and Embase for English-language studies published between January 1, 1970 and November 15, 2017 that focused on stigma reduction strategies for PWE in any global setting. Studies were included if they described a stigma reduction intervention for epilepsy. Studies were excluded if they were reviews, editorials, conference proceedings, abstracts, or did not discuss a stigma reduction intervention. We thematically grouped studies based on type(s) of intervention(s) addressed and summarized interventions, outcome measures, and results for each study included in the review. RESULTS: Of the 1975 initial citations, 32 studies met our inclusion criteria. Interventions clustered into four broad categories including public awareness interventions, policy-based interventions, school-based interventions, and interventions that targeted PWE themselves as well as their caregivers and peers. Efficacy of these interventions as reported by the authors was mixed. Many studies did not use validated outcome measures to assess stigma. CONCLUSIONS: Although intervention efforts have been made towards epilepsy stigma reduction at many levels, stigma towards and discrimination against PWE prevail worldwide. About 75% of the studies included in this review were conducted in high-income countries (HICs) despite the disproportional need in low- and middle-income countries (LMICs). Furthermore, robust outcome measures to assess efficacy in stigma reduction for interventions are lacking, calling into question the validity of reported outcomes for both positive and null findings. Therefore, more work is needed in both developing effective stigma reduction strategies, especially in LMICs, and validating tools to measure their efficacy. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Stakeholder views of the practical and cultural barriers to epilepsy care in Uganda.

OBJECTIVE: Epilepsy is one of the most prevalent, treatable neurological diseases globally. In sub-Saharan Africa, people with epilepsy (PWE) frequently seek treatment from traditional or pastoral healers, who are more accessible than biomedical care providers. This often contributes to the substantial time delay in obtaining adequate biomedical care for these patients. In Uganda, the few biomedical providers who can treat epilepsy cannot meet the great need for epilepsy care. Additionally, patients are often hesitant to seek biomedical care, often preferring the easily accessible and trusted sociocultural treatment options. This study sought to elucidate the barriers to biomedical care for PWE as well as identify potential solutions to overcome these barriers from various stakeholder perspectives. METHODS: This study used qualitative research methods. Semistructured interviews and focus group discussions were conducted with four major stakeholder groups: PWE or family members of PWE, neurologists and psychiatrists, traditional healers, and pastoral healers. All interviews and focus group discussions that were in English were audio recorded and transcribed verbatim. Those that were not in English were translated live and audio recorded. A translator later translated the non-English portion of audio recording to ensure proper interpretation. Two independent coders coded the dataset and conducted an inter-rater reliability (IRR) assessment to ensure reliable coding of the data. Thematic analysis was then performed to discern themes from the data and compare nuances between each of the study design groups. RESULTS: Participants discussed several different causes of epilepsy ranging from spiritual to biological causes, often incorporating elements of both. Commonly endorsed spiritual causes of epilepsy included witchcraft and ancestral spirits. Commonly endorsed biological causes included genetics, fever, malaria, and brain injury. For patients and families, beliefs about the cause of epilepsy often played a role in whom they chose to seek treatment from. Three major barriers to biomedical care were discussed: practical barriers, medical infrastructure barriers, and barriers related to stigma. Practical barriers related to issues such as transportation, cost of medical care, and distance to the nearest healthcare facility. Under medical infrastructure, drug stock-outs and lack of access to antiepileptic drugs (AEDs) were the most consistent problems stated among patients. Stigma was heavily discussed and brought up by nearly every participant. Additionally, three significant solutions to improving epilepsy care in Uganda were highlighted by participants: collaboration among treatment providers, community sensitization efforts to address stigma, and building medical infrastructure. Within building infrastructure, all participant types, except traditional healers, proposed the development of an epilepsy clinic designed to specifically treat epilepsy. CONCLUSIONS: Based on these findings, there are four critical interventions that should be considered for improving epilepsy care in Uganda: the creation of dedicated epilepsy clinics, infrastructure strengthening to address medication stock-outs, community outreach programs for sensitization, and collaboration between biomedical providers and traditional healers. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Leveraging the lessons learned from studies on the cultural context of epilepsy care in Uganda: Opportunities and future directions.

In this summary paper, we review the body of research contained in this special issue, The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda, and corollary recommendations for a way forward. We review key findings and conclusions for the studies, which tell a story of culture and care-seeking through discussions and data gleaned from a rich research landscape traversing community village dwellings, shared communal areas, churches, and urban hospitals. The voices and perspectives of over 16,000 study participants inclusive of people living with epilepsy, their neighbors and healthcare workers, traditional healers, and faith leaders are reported. From this, we synthesize findings and prioritize a set of recommendations to advance epilepsy care in Uganda. Progress will require infrastructure strengthening, multilevel educational investments, and an ambitious, extensive program of community sensitization. These proposed priorities and actions outline a way forward through formidable but surmountable challenges but require harmonized efforts by government and other relevant stakeholders, scholars, clinicians, and community leaders. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Barriers to biomedical care for people with epilepsy in Uganda: A cross-sectional study.

OBJECTIVE: Epilepsy, a neurological disorder with effective biomedical treatment, remains largely untreated in Uganda. Potential reasons for this treatment gap (TG) include limited access to trained providers and clinics, social stigmata of seizures, cultural beliefs, or lack of public understanding of epilepsy as a treatable condition. The current study aimed to formally evaluate barriers faced by people with epilepsy (PWE) in Uganda when seeking biomedical care. METHODS: In a cross-sectional study, 435 participants drawn from a community prevalence study were enrolled. We included participants reporting a history of recurrent seizures suggestive of epilepsy, who completed a survey about barriers to obtaining care for their symptoms. Principal axis factor analysis (PFA) using a promax rotation was conducted for data reduction. Frequencies of barrier factors were compared across those who did not seek care for epilepsy (n = 228), those who sought care from biomedical facilities (n = 166), and those who sought care from a traditional or pastoral healer (n = 41). RESULTS: The PFA yielded a five-factor solution: 1) logistical and actual costs; 2) treatment effectiveness; 3) influence of the opinion of others; 4) doctors' care; and 5) contextual factors impacting decision-making. Variables related to logistical and actual costs were most endorsed. Comparison of groups by care sought did not reveal a difference in endorsement of factors, with the exception that those who sought biomedical care were more likely to endorse factors related to doctors' care compared with those that sought care from traditional or pastoral healers (P = .005). CONCLUSIONS: People with repetitive seizures in Uganda report several barriers to obtaining biomedical care in Uganda, with those related to practical and actual costs endorsed the most. It is imperative that interventions developed to reduce the TG in Uganda consider these practical issues to improve access to effective epilepsy care. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda.

Epilepsy beliefs and misconceptions among patient and community samples in Uganda.

OBJECTIVE: The objective of the study was to characterize and compare the attitudes, beliefs, and perceptions about epilepsy across community and patient cohorts in Uganda. METHODS: This was a descriptive study utilizing two samples: a randomly selected, national survey community sample and a hospital-based patient sample of people with epilepsy (PWE) and their caregivers attending clinic settings in Kampala and Mbarara, Uganda for epilepsy care. Both samples were surveyed about their beliefs about epilepsy, its treatment, and people who have the illness. Multivariate linear regression was used to examine group differences and variables associated with specific beliefs. RESULTS: Among the 15,818 community survey participants who participated in this study, 435 study participants reported symptoms suggestive of recurrent seizures, and all 626 subjects in the hospital-based sample had confirmed epilepsy. Results revealed significant differences across groups in their endorsement of epilepsy as a contagion; 37% of people in the community unaffected by epilepsy, and 39% of people with suspected epilepsy who did not seek care believed that epilepsy was contagious by touch, in contrast to 8% of PWE or their caregivers attending regular hospital-based care. Higher educational attainment and income, and seeking regular hospital-based medical care were associated with less endorsement of epilepsy as a contagion, while age, education, income, area of residence, and presence of seizure symptoms, were significant predictors of support or belief in the basic rights of PWE. Study participants within the community who screened negative for seizures placed the most restrictions on rights for PWE. To varying degrees, the samples all endorsed the effectiveness of allopathic, traditional, and religious providers, and the use of pharmaceutical drugs, traditional rituals and herbs, and prayer. CONCLUSIONS: People with epilepsy who are attending biomedical care for routine epilepsy care think differently about epilepsy, its treatment, and the rights of those with the disease than the general population. Within the community setting, more erroneous beliefs and negative attitudes about epilepsy and PWE persist, and they not only contribute to stigma but also interfere with the patients' health-seeking behavior. Further confounding the care of PWE, the pluralistic healthcare system in Uganda is evident in endorsements spanning biomedical, traditional, and religious treatment methods. Focused awareness campaigns utilizing local epilepsy societies are needed to promote epilepsy health literacy, to favorably impact acceptance and opportunities for PWE in Uganda, and to facilitate efficient uptake of biomedical care. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Healthcare provider perspectives regarding epilepsy care in Uganda.

OBJECTIVE: Epilepsy is the most common chronic neurological disorder in the world and imposes a large economic burden on global healthcare systems, especially in low-income settings and rural areas as is found in sub-Saharan Africa (SSA). Despite the high epilepsy prevalence, there are no systematic descriptions of healthcare provider (HCP) perceptions and needs in managing people with epilepsy (PWE) in Uganda. Identifying these perceptions and needs is crucial for understanding community priorities, thereby enhancing the development of culturally sensitive communications, interventions, and research approaches. METHODS: In this qualitative study, we used semistructured interview guides to conduct focus group discussions that explored the perspectives of 32 providers of epilepsy care from health facilities around Mbarara, Uganda. Our sample included nonspecialized general physicians (n = 3), medical residents (n = 8), medical clinical officers (n = 3), psychiatric clinical nurses (n = 6), medical nurses and nursing assistants (n = 9), and other providers (n = 3), who were loosely grouped into discussion groups based on level or type of training. Self-assessed proficiency ratings were also administered to gain a better understanding of participants' confidence in their training, preparedness, and capabilities regarding epilepsy care. Thematic analysis of the focus group transcripts was conducted to ascertain commonly occurring themes about perceptions and challenges in epilepsy care. RESULTS: Our analyses identified nine major themes that dominated the perspectives of the study participants: care management, medications, diagnostics, HCP training, human resources, location, patient education, social support, and community knowledge and beliefs. Proficiency ratings prioritized areas of confidence as knowledge related to referrals, psychosocial impacts, and seizure neurophysiology. Areas of need were revealed as knowledge of diagnostic tools and antiepileptic drug (AED) regimens. CONCLUSIONS: Our findings delineate the perspectives of providers caring for PWE, with consistent recognition of challenges centering around resource augmentation, infrastructure strengthening, and education. Participants emphasized the urgent need to augment these resources to address limitations in medication types and access, trained human resources, and diagnostic tools. They overwhelmingly recognized the need for infrastructure strengthening to address human, diagnostic, medicinal, and capital resource limitations that place undue burden on patients with epilepsy and physicians. Providers indicated a clear desire to learn more about different diagnostic tools and medical management practices, potentially through continuing education, specialized training, or more intentional in-school diagnostic preparation. They also advocated for the powerful influence of patient and family education and clearly articulated the need for community sensitization and support. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Hospital-based epilepsy care in Uganda: A prospective study of three major public referral hospitals.

OBJECTIVE: This study sets out to describe the current demographics of people with epilepsy (PWE) attending hospital-based care in Uganda and the epilepsy treatment practices within three of the largest Ugandan public referral hospitals. METHODS: In a six-month prospective cohort study, 626 children and adults attending epilepsy clinics at Mulago National Referral Hospital, Butabika National Referral Mental Hospital and Mbarara Regional Referral Hospital were enrolled. Using a study questionnaire, data were collected at baseline and at 3 weeks, 3 months, and 6 months following enrollment. Specific data surrounding individual patient demographics, clinical characteristics and severity of epilepsy, and treatment of epilepsy with antiepileptic drugs (AEDs) were collected. RESULTS: Female patients totaled to 50.8%, with a nearly equal gender distribution at each hospital. There was no statistical difference in gender or age between sites. The majority of PWE had completed primary school, with less than 15% of patients completing more than a secondary education. Seizure severity was high, with most patients having multiple seizures per week at the initial onset of epilepsy, and greater than 90% of patients reporting a loss of consciousness with seizures. The majority of patients (54.95%) also reported a developmental or learning delay. Most patients were on 1 AED (46.01%) or 2 AEDs (36.90%), with carbamazepine being the most frequently prescribed AED. There was a trend towards improved seizure severity over the follow-up period, as assessed by the corresponding Personal Impact of Epilepsy Scale (PIES) subscale. CONCLUSIONS: People with epilepsy attending hospital-based care in Uganda tend to have severe forms of epilepsy requiring management with AEDs. Current hospital-based practices show a positive trend for seizure burden and quality of life of PWE in Uganda. Further interventions to improve overall access to biomedical care are required to continue to advance the management of PWE across all communities. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Sociocultural determinants and patterns of healthcare utilization for epilepsy care in Uganda.

OBJECTIVE: Epilepsy is a global public health concern, with the majority of cases occurring in lower- and middle-income countries where the treatment gap remains formidable. In this study, we simultaneously explore how beliefs about epilepsy causation, perceived barriers to care, seizure disorder characteristics, and demographics influence the initial choice of healthcare for epilepsy and its impact on attaining biomedical care (BMC). METHODS: This study utilized the baseline sample (n = 626) from a prospective cohort study of people with epilepsy (PWE) attending three public hospitals in Uganda (Mulago National Referral Hospital, Butabika National Referral Mental Hospital, and Mbarara Regional Referral Hospital) for epilepsy care. Patient and household demographics, clinical seizure disorder characteristics, and sociocultural questionnaires were administered. Logistic regression and principal component analyses (PCA) were conducted to examine associations with the choice of primary seizure treatment. RESULTS: The sample was 49% female, and 24% lived in rural settings. A biomedical health facility was the first point of care for 355 (56.7%) participants, while 229 (36.6%) first sought care from a traditional healer and 42 (6.7%) from a pastoral healer. Preliminary inspection of candidate predictors using relaxed criteria for significance (p < 0.20) identified several factors potentially associated with a greater odds of seeking BMC first. Demographic predictors included older caredriver (decision-maker for the participant) age (odds ratio [OR]: 1.01, 95% confidence interval [CI]: [0.99, 1.02], p-value: 0.09), greater caredriver education level (OR = 1.21, 95% CI: [1.07, 1.37], p-value = 0.003), and lower ratio of sick to healthy family members (OR = 0.77 [0.56, 1.05], P = 0.097). For clinical predictors, none of the proposed predictors associated significantly with seeking BMC first. Self-report causation predictors associated with a greater odds of seeking BMC first included higher belief in biological causes of epilepsy (OR = 1.31 [0.92, 1.88], P = 0.133) and lower belief in socio-spiritual causes of epilepsy (OR = 0.68 [0.56, 0.84], P < 0.001). In the multivariate model, only higher caredriver education (OR = 1.19 [1.04, 1.36], P = 0.009) and lower belief in socio-spiritual causes of epilepsy (OR = 0.69 [0.56, 0.86], P < 0.01) remained as predictors of seeking BMC first. Additionally, PCA revealed a pattern which included high income with low beliefs in nonbiological causes of epilepsy as being associated with seeking BMC first (OR = 1.32 [1.12, 1.55], p = 0.001). Despite reaching some form of care faster, individuals seeking care from traditional or pastoral healers experienced a significant delay to eventual BMC (P < 0.001), with an average delay of more than two years (traditional healer: 2.53 years [1.98, 3.24]; pastoral care: 2.18 [1.21, 3.91]). CONCLUSIONS: Coupled with low economic and educational status, belief in spiritual causation of epilepsy is a dominant determinant of opting for traditional or pastoral healing over BMC, regardless of concurrent belief in biological etiologies. There is a prolonged delay to eventual BMC for PWE who begin their treatment seeking with nonallopathic providers, and although nonallopathic healers provide PWE with benefits not provided by BMC, this notable delay likely prevents earlier administration of evidence-based care with known efficacy. Based on these findings, initiatives to increase public awareness of neurobiological causes of epilepsy and effectiveness of biomedical drug treatments may be effective in preventing delays to care, as would programs designed to facilitate cooperation and referral among traditional, faith-based, and biomedical providers. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Pluralistic and singular causal attributions for epilepsy in Uganda.

OBJECTIVE: In Uganda, causal attributions for epilepsy reflect a variety of beliefs and impact care-seeking behavior, perpetuate stigma, and undermine the effectiveness of interventions to narrow the epilepsy treatment gap. The objective of this study was to characterize beliefs about seizure etiology to gain a better understanding of how epilepsy is conceptualized in the community in order to inform culturally appropriate educational policies and interventions. METHODS: In a community-based study, 15,383 participants were surveyed about beliefs related to 15 potential causes for epilepsy. Principal axis factor analysis (PFA) was performed to identify causative factors and then utilized to classify singular versus pluralistic belief systems related to epilepsy etiology. Analysis of variance (ANOVA) and Mann-Whitney U-tests were conducted to examine the differences in background characteristics across the etiology belief groups. RESULTS: Three main causative factors emerged from the PFA: biological, sociospiritual, and biospiritual. Among those endorsing at least one factor (n = 13,036), the biological factor was endorsed most frequently as a potential cause for epilepsy (88.0%), followed by the sociospiritual (63.4%), then biospiritual (47.6%). Review of the patterns of endorsement found that only 22.2% endorsed the biological factor alone, 6.7% the sociospiritual factor alone, and 2.8% the biospiritual factor alone (total 31.7%). The remainder endorsed a combination of two or all three factors as being potentially causal, and most (65.7%) endorsed a pluralistic combination inclusive of a biological etiology. Group comparisons showed that endorsing only the biological factor was associated with the highest levels of education (p < 0.01), the pluralistic group had the highest ratio of people in the household who needed assistance to those that could provide aid (p < 0.01), and there were significant differences in income across specific groups (p < 0.01). CONCLUSIONS: Pluralistic attributions for epilepsy are common in Uganda, with the majority of community members drawing from biomedical and traditional concepts to construct complex explanations for seizures that transcend discrete belief categories traditionally depicted in the literature. These findings emphasize the need to understand cultural beliefs about epilepsy in order to design contextually specific interventions and education programs, which respect the fundamental beliefs and values of the community. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".

Treatment-resistant depression: molecular mechanisms and management.

Due to the heterogeneous nature of depression, the underlying etiological mechanisms greatly differ among individuals, and there are no known subtype-specific biomarkers to serve as precise targets for therapeutic efficacy. The extensive research efforts over the past decades have not yielded much success, and the currently used first-line conventional antidepressants are still ineffective for close to 66% of patients. Most clinicians use trial-and-error treatment approaches, which seem beneficial to only a fraction of patients, with some eventually developing treatment resistance. Here, we review evidence from both preclinical and clinical studies on the pathogenesis of depression and antidepressant treatment response. We also discuss the efficacy of the currently used pharmacological and non-pharmacological approaches, as well as the novel emerging therapies. The review reveals that the underlying mechanisms in the pathogenesis of depression and antidepressant response, are not specific, but rather involve an interplay between various neurotransmitter systems, inflammatory mediators, stress, HPA axis dysregulation, genetics, and other psycho-neurophysiological factors. None of the current depression hypotheses sufficiently accounts for the interactional mechanisms involved in both its etiology and treatment response, which could partly explain the limited success in discovering efficacious antidepressant treatment. Effective management of treatment-resistant depression (TRD) requires targeting several interactional mechanisms, using subtype-specific and/or personalized therapeutic modalities, which could, for example, include multi-target pharmacotherapies in augmentation with psychotherapy and/or other non-pharmacological approaches. Future research guided by interaction mechanisms hypotheses could provide more insights into potential etiologies of TRD, precision biomarker targets, and efficacious therapeutic modalities.

Neuropsychological normative standards for late career physicians.

Objective: In the context of an aging, vital physician workforce, there is clear value in establishing a specialized neuropsychological normative dataset for the evaluation of late career physicians practicing clinical medicine. Methods: Physicians aged 60 and over in active clinical practice at 3 major medical centers in North Carolina were recruited to complete a comprehensive neuropsychological test battery. Results: The sample (n = 100) was aged 60-78. Reflecting medical school distributions for this age group, the sample was mostly male (76%) and was fairly racially homogenous (96% White). To amplify utility of the dataset, data were obtained for several measures across neurocognitive domains. Results are presented in percentile bands stratified by age and sex where needed, and regression formulas are presented for predictive precision for measures where both age and sex predicted performance. Important distinctions between our sample, the general population, and current comparative demographic norms were also confirmed. Conclusions: Here we present a preliminary normative dataset on a comprehensive neuropsychological test battery for late career physicians, the HEATS norms for highly educated aging treaters. These standards facilitate accurate, objective cognitive measurement as a part of clinical diagnostic and capacity evaluations. Co-norming the battery in a single, specialized sample further augments its utility in characterizing cognition. Future work to enhance the dataset to be maximally applicable across demographic groups is anticipated, as is research to explore the relationship between these standards and professional performance outcomes.

RECOVER-NEURO: study protocol for a multi-center, multi-arm, phase 2, randomized, active comparator trial evaluating three interventions for cognitive dysfunction in post-acute sequelae of SARS-CoV-2 infection (PASC).

BACKGROUND: Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as "brain fog" and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work. METHODS: RECOVER-NEURO is a prospective, multi-center, multi-arm, phase 2, randomized, active-comparator design investigating 3 interventions: (1) BrainHQ is an interactive, online cognitive training program; (2) PASC-Cognitive Recovery is a cognitive rehabilitation program specifically designed to target frequently reported challenges among individuals with brain fog; (3) transcranial direct current stimulation (tDCS) is a noninvasive form of mild electrical brain stimulation. The interventions will be combined to establish 5 arms: (1) BrainHQ; (2) BrainHQ + PASC-Cognitive Recovery; (3) BrainHQ + tDCS-active; (4) BrainHQ + tDCS-sham; and (5) Active Comparator. The interventions will occur for 10 weeks. Assessments will be completed at baseline and at the end of intervention and will include cognitive testing and patient-reported surveys. All study activities can be delivered in Spanish and English. DISCUSSION: This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different mechanisms of action and with prior evidence of improving cognitive function in patients with neurocognitive disorder. If successful, results will provide beneficial treatments for PASC-related cognitive dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05965739. Registered on July 25, 2023.

A prospective randomized study examining the impact of intravenous versus inhalational anesthesia on postoperative cognitive decline and delirium.

The present prospective randomized study was designed to investigate whether the development of Post Operative Cognitive Decline (POCD) is related to anesthesia type in older adults. All patients were screened for delirium and mental status, received baseline neuropsychological assessment, and evaluation of activities of daily living (ADLs). Follow-up assessments were performed at 3-6 months and 12-18 months. Patients were randomized to receive either inhalation anesthesia (ISO) with isoflurane or total intravenous anesthesia (TIVA) with propofol for maintenance anesthesia. ISO (n = 99) and TIVA (n = 100) groups were similar in demographics, preoperative cognition, and incidence of post-operative delirium. Groups did not differ in terms of mean change in memory or executive function from baseline to follow-up. Pre-surgical cognitive function is the only variable predictive of the development of POCD. Anesthetic type was not predictive of POCD. However, ADLs were predictive of post-operative delirium development. Overall, this pilot study represents a prospective, randomized study demonstrating that when examining ISO versus TIVA for maintenance of general anesthesia, there is no significant difference in cognition between anesthetic types. There is also no difference in the occurrence of postoperative delirium. Postoperative cognitive decline was best predicted by lower baseline cognition and functional status.

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.