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Epilepsia Open Jun 2024The main goal of presurgical evaluation in drug-resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource-intensive tests...
Determinants of successful ictal SPECT injection in phase 1 epilepsy presurgical evaluation: Findings from the pediatric epilepsy research consortium surgery database project.
OBJECTIVES
The main goal of presurgical evaluation in drug-resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource-intensive tests available, ictal single-photon emission computed tomography (SPECT) aids SOZ localization by measuring focal increases in blood flow within the SOZ via intravenous peri-ictal radionuclide administration. Recent studies indicate that geographic and center-specific factors impact utilization of these diagnostic procedures. Our study analyzed successful ictal SPECT acquisition (defined as peri-ictal injection during inpatient admission) using surgery-related data from the Pediatric Epilepsy Research Consortium (PERC) surgery database. We hypothesized that a high seizure burden, longer duration of video EEG monitoring (VEEG), and more center-specific hours of SPECT availability would increase the likelihood of successful ictal SPECT.
METHODS
We identified study participants (≤18 years of age) who underwent SPECT as part of their phase 1 VEEG from January 2018 to June 2022. We assessed association between ictal SPECT outcomes (success vs. failure) and variables including patient demographics, epilepsy history, and center-specific SPECT practices.
RESULTS
Phase 1 VEEG monitoring with ictal SPECT injection was planned in 297 participants and successful in 255 participants (85.86%). On multivariable analysis, the likelihood of a successful SPECT injection was higher in patients of non-Hispanic ethnicity (p = 0.040), shorter duration VEEG (p = 0.004), and higher hours of available SPECT services (p < 0.001). Higher seizure frequency (p = 0.033) was significant only in bivariate analysis. Patients treated at centers with more operational hours were more likely to experience pre-admission protocols prior to VEEG (p = 0.002).
SIGNIFICANCE
There is inter-center variability in protocols and SPECT acquisition capabilities. Shorter duration of EEG monitoring, non-Hispanic ethnicity (when on private insurance), extended operational hours of nuclear medicine as noted on multivariate analysis and higher seizure frequency in bivariate analysis are strongly associated with successful ictal SPECT injection.
PLAIN LANGUAGE SUMMARY
In pediatric patients with drug-resistant epilepsy, single-photon emission computed tomography (SPECT) scans can be helpful in localizing seizure onset zone. However, due to many logistical challenges described below, which include not only the half-life of the technetium isotope used to inject intravenously during a seizure (called the ictal SPECT scan) but also available nuclear scanner time in addition to the unpredictability of seizures, obtaining an ictal SPECT during a planned elective inpatient hospital stay is not guaranteed. Thus, as healthcare costs increase, planning a prolonged hospital stay during which an ictal SPECT scan is not feasible is not optimal. We leveraged our prospective surgery database to look at center-specific factors and patient-specific factors associated with an ictal SPECT injection in the first, pediatric-focussed, large-scale, multicenter, prospective, SPECT feasibility study. We found that longer availability of the scanner is the most important center-specific factor in assuring ictal SPECT injection. Although seizure frequency is an important patient-specific factor on bivariate analysis, this factor lost statistical significance when other factors like patient insurance status and video EEG duration were also considered in our multivariable logistical model.
PubMed: 38845472
DOI: 10.1002/epi4.12986 -
Implementation Science Communications Jun 2024Despite increasing morbidity and mortality from non-communicable diseases (NCD) globally, health systems in low- and middle-income countries (LMICs) have limited...
Evaluating a multifaceted implementation strategy and package of evidence-based interventions based on WHO PEN for people living with HIV and cardiometabolic conditions in Lusaka, Zambia: protocol for the TASKPEN hybrid effectiveness-implementation stepped wedge cluster randomized trial.
BACKGROUND
Despite increasing morbidity and mortality from non-communicable diseases (NCD) globally, health systems in low- and middle-income countries (LMICs) have limited capacity to address these chronic conditions, particularly in sub-Saharan Africa (SSA). There is an urgent need, therefore, to respond to NCDs in SSA, beginning by applying lessons learned from the first global response to any chronic disease-HIV-to tackle the leading cardiometabolic killers of people living with HIV (PLHIV). We have developed a feasible and acceptable package of evidence-based interventions and a multi-faceted implementation strategy, known as "TASKPEN," that has been adapted to the Zambian setting to address hypertension, diabetes, and dyslipidemia. The TASKPEN multifaceted implementation strategy focuses on reorganizing service delivery for integrated HIV-NCD care and features task-shifting, practice facilitation, and leveraging HIV platforms for NCD care. We propose a hybrid type II effectiveness-implementation stepped-wedge cluster randomized trial to evaluate the effects of TASKPEN on clinical and implementation outcomes, including dual control of HIV and cardiometabolic NCDs, as well as quality of life, intervention reach, and cost-effectiveness.
METHODS
The trial will be conducted in 12 urban health facilities in Lusaka, Zambia over a 30-month period. Clinical outcomes will be assessed via surveys with PLHIV accessing routine HIV services, and a prospective cohort of PLHIV with cardiometabolic comorbidities nested within the larger trial. We will also collect data using mixed methods, including in-depth interviews, questionnaires, focus group discussions, and structured observations, and estimate cost-effectiveness through time-and-motion studies and other costing methods, to understand implementation outcomes according to Proctor's Outcomes for Implementation Research, the Consolidated Framework for Implementation Research, and selected dimensions of RE-AIM.
DISCUSSION
Findings from this study will be used to make discrete, actionable, and context-specific recommendations in Zambia and the region for integrating cardiometabolic NCD care into national HIV treatment programs. While the TASKPEN study focuses on cardiometabolic NCDs in PLHIV, the multifaceted implementation strategy studied will be relevant to other NCDs and to people without HIV. It is expected that the trial will generate new insights that enable delivery of high-quality integrated HIV-NCD care, which may improve cardiovascular morbidity and viral suppression for PLHIV in SSA. This study was registered at ClinicalTrials.gov (NCT05950919).
PubMed: 38844992
DOI: 10.1186/s43058-024-00601-z -
BMJ Open Jun 2024Globally, the number of children/adolescents exposed to HIV but uninfected (HIV-exposed uninfected, HEU) is growing. The HEU outcomes: population-evaluation and... (Comparative Study)
Comparative Study
PURPOSE
Globally, the number of children/adolescents exposed to HIV but uninfected (HIV-exposed uninfected, HEU) is growing. The HEU outcomes: population-evaluation and screening strategies study was designed to provide population-level evidence of the impact of HIV and recent antiretroviral therapy regimen exposure on neurodevelopmental, hearing and mental health outcomes from infancy to adolescence.
PARTICIPANTS
The study includes a prospective mother-infant cohort and cross-sectional child/youth-caregiver cohorts conducted in Kenya.Between 2021 and 2022, the study enrolled 2000 mother-infant pairs (1000 HEU and 1000 HIV-unexposed uninfected (HUU)) for longitudinal follow-up. Infants were eligible if they were aged 4-10 weeks and healthy. Mothers were eligible if their HIV status was known and were ≥18 years. Study visits are 6 monthly until the child reaches age 3 years.Cross-sectional cohorts spanning ages 3-18 years started enrolment in 2022. Target enrolment is 4400 children/youth (4000 HEU and 400 HUU). Children and youth are eligible if they are HIV negative, maternal HIV status and timing of diagnosis is known, and caregivers are ≥18 years.Data on infant/child/youth growth, neurodevelopment, mental health, morbidity and hearing are collected at enrolment using standardised tools. Dry blood spots samples are collected for telomere length assessment at baseline and yearly for the longitudinal cohort. Growth z-scores, neurodevelopmental scores, telomere length and prevalence of developmental and hearing problems will be compared between HEU/HUU populations.
FINDINGS TO DATE
Full cohort enrolment for the longitudinal cohort is complete and participants are in follow-up. At 1 year of age, comparing HEU to HUU neurodevelopment using the Malawi developmental assessment tool, we found that HEU infants had higher language scores and comparable scores in fine motor, gross motor and social scores. The cross-sectional cohort has enrolled over 2000 participants and recruitment is ongoing.
FUTURE PLANS
Longitudinal cohort follow-up and enrolment to the cross-sectional study will be completed in June 2024.
Topics: Humans; Kenya; Female; Child; HIV Infections; Child, Preschool; Adolescent; Infant; Cross-Sectional Studies; Longitudinal Studies; Male; Prospective Studies; Pregnancy; Adult; Infectious Disease Transmission, Vertical; Pregnancy Complications, Infectious
PubMed: 38844397
DOI: 10.1136/bmjopen-2023-081975 -
Current Opinion in HIV and AIDS Jul 2024Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy... (Review)
Review
PURPOSE OF REVIEW
Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy (ART), as modeled in Simian immunodeficiency virus (SIV) and Simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and observed in clinical trials. This review outlines mode of transmission, pathogenesis of pediatric HIV, unique aspects of the infant immune system, infant macaque models and immunotherapies.
RECENT FINDINGS
During the earliest stages of perinatal HIV infection, the infant immune system is characterized by a unique environment defined by immune tolerance and lack of HIV-specific T cell responses which contribute to disease progression. Moreover, primary lymphoid organs such as the thymus appear to play a distinct role in HIV pathogenesis in children living with HIV (CLWH). Key components of the immune system determine the degree of viral control, targets for strategies to induce viral control, and the response to immunotherapy. The pursuit of highly potent broadly neutralizing antibodies (bNAbs) and T cell vaccines has revolutionized the approach to HIV cure. Administration of HIV-1-specific bNAbs, targeting the highly variable envelope improves humoral immunity, and T cell vaccines induce or improve T cell responses such as the cytotoxic effects of HIV-1-specific CD8+ T cells, both of which are promising options towards virologic control and ART-free remission as evidenced by completed and ongoing clinical trials.
SUMMARY
Understanding early events during HIV infection and disease progression in CLWH serves as a foundation for predicting or targeting later outcomes by harnessing the immune system's natural responses. The developing pediatric immune system offers multiple opportunities for specific long-term immunotherapies capable of improving quality of life during adolescence and adulthood.
Topics: Humans; HIV Infections; Immunotherapy; Animals; Child; Macaca mulatta; Disease Models, Animal; Infant; Simian Immunodeficiency Virus; AIDS Vaccines
PubMed: 38841850
DOI: 10.1097/COH.0000000000000857 -
International Journal of MCH and AIDS 2024Understanding the preferences of women living with HIV (WLH) for the prevention of mother-to-child HIV transmission (PMTCT) services is important to ensure such services...
BACKGROUND AND OBJECTIVE
Understanding the preferences of women living with HIV (WLH) for the prevention of mother-to-child HIV transmission (PMTCT) services is important to ensure such services are person-centered.
METHODS
From April to December 2022, we surveyed pregnant and postpartum WLH enrolled at five health facilities in western Kenya to understand their preferences for PMTCT services. WLH were stratified based on the timing of HIV diagnosis: known HIV-positive (KHP; before antenatal clinic [ANC] enrollment), newly HIV-positive (NHP; on/after ANC enrollment). Multivariable logistic regression was used to determine associations between various service preferences and NHP (vs. KHP) status, controlling for age, facility, gravidity, retention status, and pregnancy status.
RESULTS
Among 250 participants (median age 31 years, 31% NHP, 69% KHP), 93% preferred integrated versus non-integrated HIV and maternal-child health (MCH) services; 37% preferred male partners attend at least one ANC appointment (vs. no attendance/no preference); 54% preferred support groups (vs. no groups; 96% preferred facility - over community-based groups); and, preferences for groups was lower among NHP (42%) versus KHP (60%). NHP had lower odds of preferring support groups versus KHP (aOR 0.45, 95% CI 0.25-0.82), but not the other services.
CONCLUSION AND GLOBAL HEALTH IMPLICATIONS
Integrated services were highly preferred by WLH, supporting the current PMTCT service model in Kenya. Further research is needed to explore the implementation of facility-based support groups for WLH as well as the reasons underlying women's preferences.
PubMed: 38840934
DOI: 10.25259/IJMA_6_2024 -
BMC Public Health Jun 2024HIV-related stigma and discrimination significantly affects health, and well-being, willingness to be tested for HIV, initiation and adherence to antiretroviral therapy,...
Individual and community level factors associated with discriminatory attitudes against people living with HIV/AIDS among women of reproductive age in three sub-Saharan African countries: evidence from the most recent demographic and health survey (2021/22).
INTRODUCTION
HIV-related stigma and discrimination significantly affects health, and well-being, willingness to be tested for HIV, initiation and adherence to antiretroviral therapy, and quality of life. However, the findings of the prior studies revealed that the prevalence of discrimination against people living with HIV is high. Thus, we aimed to assess the magnitude of discriminatory attitudes against people living with HIV/AIDS and associated factors in three sub-Saharan African countries.
METHODS
The appended and most recent Demographic and Health Survey dataset of three sub-Saharan African countries from 2021 to 2022 was used for data analysis. A total of 56,690 women aged 15-49 years were included in this study as a weighted sample. The determinants of discriminatory attitudes against people living with HIV/AIDS were determined using a multilevel mixed-effects logistic regression model. Significant factors associated with discriminatory attitudes against people living with HIV/AIDS in the multilevel mixed-effect logistic regression model were declared significant at p-values < 0.05. The adjusted odds ratio (AOR) and confidence interval (CI) were used to interpret the results.
RESULT
The overall prevalence of discriminatory attitudes against people living with HIV/AIDS was 28.19% (95% CI: 27.74%, 28.64%). In the multivariable analysis, individual level (being young, being an internet user, being tested for HIV, and having comprehensive knowledge about HIV) and community level (being a rural dweller) were factors associated with discriminatory attitudes against people living with HIV/AIDS.
CONCLUSION
The prevalence of discriminatory attitudes against people living with HIV/AIDS in three sub-Saharan African countries was high. Individual and community-level variables were associated with discriminatory attitudes against people living with HIV/AIDS. Therefore, special consideration should be given to rural dwellers and young adults. In addition, better to strengthen the accessibility of Internet and HIV testing services, and improve HIV-related education to reduce the magnitude of discriminatory attitudes against people living with HIV/AIDS.
Topics: Humans; Female; Adult; Adolescent; Middle Aged; Young Adult; HIV Infections; Health Surveys; Social Stigma; Africa South of the Sahara; Prejudice
PubMed: 38840148
DOI: 10.1186/s12889-024-19022-7 -
Med (New York, N.Y.) May 2024This study aims to estimate the burden, trends, forecasts, and disparities of early musculoskeletal (MSK) disorders among individuals ages 15 to 39 years.
BACKGROUND
This study aims to estimate the burden, trends, forecasts, and disparities of early musculoskeletal (MSK) disorders among individuals ages 15 to 39 years.
METHODS
The global prevalence, years lived with disabilities (YLDs), disability-adjusted life years (DALYs), projection, and inequality were estimated for early MSK diseases, including rheumatoid arthritis (RA), osteoarthritis (OA), low back pain (LBP), neck pain (NP), gout, and other MSK diseases (OMSKDs).
FINDINGS
More adolescents and young adults were expected to develop MSK disorders by 2050. Across five age groups, the rates of prevalence, YLDs, and DALYs for RA, NP, LBP, gout, and OMSKDs sharply increased from ages 15-19 to 35-39; however, these were negligible for OA before age 30 but increased notably at ages 30-34, rising at least 6-fold by 35-39. The disease burden of gout, LBP, and OA attributable to high BMI and gout attributable to kidney dysfunction increased, while the contribution of smoking to LBP and RA and occupational ergonomic factors to LBP decreased. Between 1990 and 2019, the slope index of inequality increased for six MSK disorders, and the relative concentration index increased for gout, NP, OA, and OMSKDs but decreased for LBP and RA.
CONCLUSIONS
Multilevel interventions should be initiated to prevent disease burden related to RA, NP, LBP, gout, and OMSKDs among individuals ages 15-19 and to OA among individuals ages 30-34 to tightly control high BMI and kidney dysfunction.
FUNDING
The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation. The project is funded by the Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).
PubMed: 38834074
DOI: 10.1016/j.medj.2024.04.009 -
The Journal of Clinical Investigation Jun 2024Despite effective antiretroviral therapy (ART), persons living with HIV (PWH) harbor reservoirs of persistently infected CD4+ cells, which constitute a barrier to cure....
Despite effective antiretroviral therapy (ART), persons living with HIV (PWH) harbor reservoirs of persistently infected CD4+ cells, which constitute a barrier to cure. Initiation of ART during acute infection reduces the size of the HIV reservoir, and we hypothesized that in addition, it would favor integration of proviruses in HIV-specific CD4+ T cells, while initiation of ART during chronic HIV infection would favor relatively more proviruses in herpesvirus-specific cells. We further hypothesized that proviruses in acute-ART-initiators would be integrated into antiviral genes, whereas integration sites in chronic-ART-initiators would favor genes associated with cell proliferation and exhaustion. We found the HIV DNA distribution across HIV-specific vs. herpesvirus-specific CD4+ T cells was as hypothesized. HIV integration sites (IS) in acute-ART-initiators were significantly enriched in gene sets controlling lipid metabolism and HIF-1α-mediated hypoxia, both metabolic pathways active in early HIV infection. Persistence of these infected cells during prolonged ART suggests a survival advantage. IS in chronic-ART-initiators were enriched in a gene set controlling EZH2 histone methylation; and methylation has been associated with diminished LTR transcription. These differences we found in antigen specificities and IS distributions within HIV-infected cells might be leveraged in designing cure strategies tailored to the timing of ART initiation.
PubMed: 38833307
DOI: 10.1172/JCI159569 -
Research Square May 2024one of the pathogens strongly implicated in hospital infections. Data on the resistance and molecular characteristics of this bacterium are rare in Mali.
BACKGROUND
one of the pathogens strongly implicated in hospital infections. Data on the resistance and molecular characteristics of this bacterium are rare in Mali.
OBJECTIVE
This study aimed to evaluate the antibiotic resistance patterns, virulence factors of isolates from pleural fluid infections in hospitalized patients.
METHODS
Pleural effusion samples were obtained by thoracentesis for bacteriological examination from October 2021 to December 2022 at the "Hôpital du Mali" teaching hospital. Comorbidities such as HIV/AIDS and diabetes were assessed. Standard microbiological procedures were used for bacterial identification. The disk diffusion method was used to identify methicillin-resistant . The PCR amplification method was used to detect the following genes: , , , , and .
RESULTS
This study analyzed 6096 samples from inpatients and found a pooled frequency of bacterial pleuritis of 526 (8.6%) in thoracic surgery and pediatric wards. was isolated in 52 (9.88%) cases, of which 39 (75%) isolates were MRSA. There was no significant difference between the sexes (). The median age of the patients was 30 years. All isolates showed resistance to penicillin-G. The leucocidin toxin was detected in 7.7% of thoracic surgery patients, but , , , and toxins were not found.
CONCLUSION
In this study, we found a high frequency of (and MRSA) in pleurisy patients at the "Hôpital du Mali". Only the leukocidin was found. The empirical treatment protocol for pleurisy may need revision. Clindamycin, linezolid, teicoplanin, daptomycin, fosfomycin, vancomycin, moxifloxacin and fusidic acid were the most active antibiotics on our isolates in this study. Infection prevention measures, active surveillance, and effective therapeutic options are recommended.
PubMed: 38826428
DOI: 10.21203/rs.3.rs-3579825/v1 -
International Journal of Surgery Case... Jul 2024Colocolic intussusception occur in less than 5 % of all cases of intussusception. Median age at presentation is 4.4 years. Usually presents with features of intestinal...
INTRODUCTION AND IMPORTANCE
Colocolic intussusception occur in less than 5 % of all cases of intussusception. Median age at presentation is 4.4 years. Usually presents with features of intestinal obstruction. Common causes include pathological lead points like juvenile polyps, Meckel's diverticulum and lymphoma. However, rarely occurs without an organic cause as presented in the index case.
CASE PRESENTATION
We present a case of colocolic intussusception in a 5-year-old boy with clinical evidence of blood-stained mucoid stools, abdominal distention and post prandial vomiting. CT-scan confirmed the clinical diagnosis. Surgical exploration revealed left-sided colocolic intussusception without a pathological lead point.
CLINICAL DISCUSSION
Most cases of colonic intussusception have a pathological lead point. Clinical features are unspecific but mostly present with intestinal obstruction, hence, a CT-scan aids in establishing the diagnosis.
CONCLUSION
Colocolic intussusception is a rare subtype of intussusception in the paediatric age group especially in the absence of a pathological lead point. This case report presents a rare case of colocolic intussusception without pathological lead point, highlighting the importance of advanced imaging modalities like CT-scan in establishing the diagnosis and guiding management.
PubMed: 38824742
DOI: 10.1016/j.ijscr.2024.109841