Cohort profile: the South African National Health Laboratory Service (NHLS) National HIV Cohort.

PURPOSE: South Africa's National Health Laboratory Service (NHLS) National HIV Cohort was established in 2015 to facilitate monitoring, evaluation and research on South Africa's National HIV Treatment Programme. In South Africa, 84.8% of people living with HIV know their HIV status; 70.7% who know their status are on ART; and 87.4% on ART are virologically suppressed. PARTICIPANTS: The NHLS National HIV Cohort includes the laboratory data of nearly all patients receiving HIV care in the public sector since April 2004. Patients are included in the cohort if they have received a CD4 count or HIV RNA viral load (VL) test. Using an anonymised unique patient identifier that we have developed and validated to linked test results, we observe patients prospectively through their laboratory results as they receive HIV care and treatment. Patients in HIV care are seen for laboratory monitoring every 6-12 months. Data collected include age, sex, facility location and test results for CD4 counts, VLs and laboratory tests used to screen for potential treatment complications. FINDINGS TO DATE: From April 2004 to April 2018, 63 million CD4 count and VL tests were conducted at 5483 facilities. 12.6 million unique patients had at least one CD4 count or VL, indicating they had accessed HIV care, and 7.1 million patients had a VL test indicating they had started antiretroviral therapy. The creation of NHLS National HIV Cohort has enabled longitudinal research on all lab-monitored patients in South Africa's national HIV programme, including analyses of (1) patient health at presentation; (2) care outcomes such as 'CD4 recovery', 'retention in care' and 'viral resuppression'; (3) patterns of transfer and re-entry into care; (4) facility-level variation in care outcomes; and (5) impacts of policies and guideline changes. FUTURE PLANS: Continuous updating of the cohort, integration with available clinical data, and expansion to include tuberculosis and other lab-monitored comorbidities.

Using national laboratory data to assess cumulative frequency of linkage after transfer to community-based HIV clinics in South Africa.

INTRODUCTION: Changes to the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) funding have led to closures of non-governmental HIV clinics with patient transfers to government-funded clinics. We sought to determine the success of transfers in South Africa using a national data source. METHODS: All adults (≥18 years) on antiretroviral therapy (ART) who visited a single PEPFAR-funded hospital-based HIV clinic in Durban, South Africa from March to June 2012 were transferred to community-based clinics. Previously, we matched patient records from the hospital-based HIV clinic with National Health Laboratory Services (NHLS) Corporate Data Warehouse (CDW) data to estimate the proportion of patients with a CD4 count or viral load (VL) in the CDW during the year before transfer. As a proxy for retention in care, in this study we evaluated whether patients had a CD4 count or VL at another facility within approximately three years of transfer. Patients referred to a private doctor at transfer were excluded from the analysis. We assessed predictors (age, sex, CD4 count, VL status, ART duration and location of future care) of not having post-transfer laboratory data using Cox proportional hazards models. RESULTS: Of the 3893 patients referred to a government facility at transfer, 41% were male and median age was 39 years (IQR 34 to 46). There was a post-transfer CD4 count or VL from another facility for 23% of these individuals within six months, 44% within one year, 57% within two years and 61% within approximately three years. Male sex (aHR 1.20, 95% CI 1.10 to 1.31) and shorter duration on ART (<3 months, aHR 3.80, 95% CI 2.77 to 5.21; three months to one year, aHR 1.32, 95% CI 1.15 to 1.51, each compared with >1 year) were associated with not having a post-transfer record. CONCLUSIONS: Using data from the NHLS CDW, 61% of patients had evidence of a post-transfer laboratory record at another facility within approximately three years after closure of a large South African HIV clinic. Males and those with shorter time on ART prior to transfer were at highest risk for lacking follow-up laboratory data. As patients transfer care, national data sources can be used to evaluate long-term patient care trajectories.

Assessing the completeness and accuracy of South African National Laboratory CD4 and viral load data: a cross-sectional study.

OBJECTIVE: To assess the accuracy of the South African National Health Laboratory Services (NHLS) corporate data warehouse (CDW) using a novel data cross-matching method. METHODS: Adults (≥18 years) on antiretroviral therapy (ART) who visited a hospital-based HIV clinic in Durban from March to June 2012 were included. We matched patient identifiers, CD4 and viral load (VL) records from the HIV clinic's electronic record with the NHLS CDW according to a set of matching criteria for patient identifiers, test values and test dates. We calculated the matching rates for patient identifiers, CD4 and VL records, and an overall matching rate. RESULTS: NHLS returned records for 3498 (89.6%) of the 3906 individuals requested. Using our computer algorithm, we confidently matched 3278 patients (83.9% of the total request). Considering less than confident matches as well, and then manually reviewing questionable matches using only patient identifiers, only nine (0.3% of records returned by NHLS) of the suggested matches were judged incorrect. CONCLUSIONS: We developed a data cross-matching method to evaluate national laboratory data and were able to match almost 9 of 10 patients with data we expected to find in the NHLS CDW. We found few questionable matches, suggesting that manual review of records returned was not essential. As the number of patients initiating ART in South Africa grows, maintaining a comprehensive and accurate national data repository is of critical importance, since it may serve as a valuable tool to evaluate the effectiveness of the country's HIV care system. This study helps validate the use of NHLS CDW data in future research on South Africa's HIV care system and may inform analyses in similar settings with national laboratory systems.

Using mHealth to improve tuberculosis case identification and treatment initiation in South Africa: Results from a pilot study.

BACKGROUND: Tuberculosis (TB) incidence in South Africa is among the highest globally. Initial loss to follow-up (ILFU), defined as not starting on TB treatment within 28 days of testing positive, is undermining control efforts. We assessed the feasibility, acceptability, and potential of a mHealth application to reduce ILFU. METHODS: An mHealth application was developed to capture patients TB investigation data, provide results and monitor treatment initiation. This was implemented in two primary health clinics (PHC) in inner-city Johannesburg. Feasibility was assessed by comparing documentation of personal details, specimen results for same individuals during implementation period (paper register and Mhealth application). Effectiveness was assessed by comparing proportion of patients with results within 48 hours, and proportion started on treatment within 28 days of testing TB positive during pre- implementation (paper register) and implementation (mHealth application) periods. In-depth interviews with patients and providers were conducted to assess acceptability of application. RESULTS: Pre-implementation, 457 patients were recorded in paper registers [195 (42.7%) male, median age 34 years (interquartile range IQR (28-40), 45 (10.5%) sputum Xpert positive]. During implementation, 319 patients were recorded in paper register and the mHealth application [131 (41.1%) male, median age 32 years (IQR 27-38), 33 (10.3%) sputum Xpert positive]. The proportion with complete personal details: [mHealth 95.0% versus paper register 94.0%, (p = 0.54)] and proportion with documented results: [mHealth 97.4% versus paper register 97.8%, (p = 0.79)] were not different in the two methods. The proportion of results available within 48 hours: [mHealth 96.8% versus paper register 68.6%), (p <0.001)], and the proportion on treatment within 28 days [mHealth 28/33 (84.8%) versus paper register 30/44 (68.2%), (p = 0.08)] increased during implementation but was not statistically significant. In-depth interviews showed that providers easily integrated the mHealth application into routine TB investigation and patients positively received the delivery of results via text message. Time from sputum collection to TB treatment initiation decreased from 4 days (pre-implementation) to 3 days but was not statistically significant. CONCLUSIONS: We demonstrated that implementation of the mHealth application was feasible, acceptable to health care providers and patients, and has potential to reduce the time to TB treatment initiation and ILFU in PHC settings.

Velocardiofacial syndrome in Mexican patients: Unusually high prevalence of congenital heart disease.

INTRODUCTION: Velocardiofacial syndrome (VCFS) is the most common microdeletion syndrome with an incidence of 1:4000 live births. Its phenotype is highly variable with facial, velopharyngeal, cardiac, endocrine, immunologic and psychiatric abnormalities. It is caused by a microdeletion in chromosome 22q11.2. OBJECTIVES: We present 7 years of experience evaluating patients with VCFS regarding their main clinical characteristics. MATERIAL AND METHODS: The patients included were multidisciplinary evaluated and had a positive FISH analysis for del22q11.2. RESULTS: A total of 62 patients were assessed, a 34 female/28 male ratio was observed with ages ranging from 9 days to 16 years, all but one patient had typical facial features. A diagnosis of congenital heart disease was established in 97% of the patients; other clinical characteristics were identified with different percentages such as cleft palate, and hypocalcaemia. Three cases had a familial presentation. DISCUSSION: While the clinical findings of this study were in general terms in keeping with the literature, it is interesting the unexpectedly high percentage of congenital heart disease identified in Mexican children with VCFS that also was the main cause for clinical referral.

Importancia del diagnóstico de mutaciones en el gen de la conexina 26 en el manejo integral de la sordera congénita no sindrómica / Importance of the diagnosis of connexin 26 gene mutations in the integral management of non-syndromic congenital deafness

Introducción. La sordera congénita es un problema de salud pública. Su incidencia en México es de 2-3 por cada 1000 recién nacidos. El diagnóstico oportuno con el tamiz auditivo neonatal es fundamental para un mejor pronóstico funcional. Aproximadamente 70% de las sorderas congénitas son de origen genético, con herencia autosómica recesiva. La mayoría de estos casos se asocia con mutaciones en el gen GJB2 , que codifica para la proteína conexina 26. Hay tres mutaciones reportadas como las más frecuentes en este gen: c.35delG, c.167delT y c.235delC. Métodos. Previo consentimiento informado de los pacientes, se obtuvo 1 ml de sangre periférica para la extracción de ADN. Mediante las técnicas de PCR-RFLP o PCR seguida de secuenciación, se buscaron las tres mutaciones más frecuentes del gen GJB2 . Resultados. Se realizó el estudio molecular en 11 pacientes: Se encontró un cambio en la secuencia codificante en cinco de ellos. Un paciente fue homocigoto para c.35delG; otro resultó heterocigoto para c.35insG, mutación no reportada previamente; un tercero fue heterocigoto para c.34G>T y dos más fueron heterocigotos para el polimorfismo c.79G>A (p.V27I). En ningún caso se hallaron las mutaciones c.167delT y c.235delC. Conclusiones. Se encontraron cambios de secuencias que correspondieron a dos polimorfismos y a tres mutaciones. La frecuencia de las tres mutaciones investigadas fue menor a lo reportado en la literatura y se encontró una mutación no reportada previamente. Este estudio evidencia la importancia del diagnóstico oportuno con manejo integral, incluyendo el asesoramiento genético con base en estudios moleculares, y resalta la importancia de conocer el perfil genotípico de este grupo de pacientes.

Background. Congenital deafness is a public health problem affecting 2-3:1000 newborns in Mexico. Neonatal audiologic screening allows early detection with important implications for the functional prognosis. About 70% of cases of congenital deafness are associated with a genetic etiology with an autosomal recessive pattern of inheritance. Most cases are caused by mutations in the GJB2 gene, which codifies conexin 26. The three most commonly reported mutations in this gene are c.35delG, c.167delT and c.235delC. Methods. After obtaining informed consent, DNA was extracted from a blood sample, and the three previously mentioned mutations were searched for using PCR-RFLP or PCR followed by sequencing. Results. Molecular analysis was carried out in 11 patients. In five of these patients, a change in sequence was observed. In none of the patients were c.167delT and c.235delC mutations found. One patient was homozygous for c.35delG and another patient was heterozygous for c.35insG, which is a mutation not previously reported. A third patient was heterozygous for c.34G>T. Two additional patients had the c.79G>A (p.V27I) polymorphism. Conclusions. Frequency of the three mutations analyzed was lower compared to other populations. Five sequence changes were observed, two polymorphisms and three mutations, one of them novel. This study also demonstrates the relevance of early diagnosis and multidisciplinary management and the importance of determining the genetic basis of this disease in pediatric patients with congenital deafness.

Estandarización de los datos reportados en estudios de nasofaringoscopía y fluoroscopía del esfínter velofaríngeo / Stantardization of data reported in studies of nasopharyngoscopy and fluoroscopy of the velopharyngeal sphincter

Existe una gran inquietud mundial por inicar el informe de los hallazgos obtenidos con la endoscopía con fibra óptica y con la fluoroscopía en el esfínter velofaríngeo. La evolución debe ser realizada por un médico especialista (foniatría). Nasofaringoscopía: el equipo necesario es el nasofaringoscopio con frente de luz. La videograbación es deseable, pero no indispensable. El reporte debe ser discriptivo y llegar a conclusiones precisas sobre 1) fosa nasal: 2) meatro; 3) orificio de la salida de la trompa de eustaquio; 4) orofaringeo; 5) esfinter velofaríngeo (paredes faríngeas posterior y laterales y velo de paladar), 6)patrón de cierre (forma y cada estructura por separado, en reposo y fonación); 7) laringe. Flouroscopía; útil para valorar las parederes faríngeas laterales y el nivel de cierre del esfínter velofaríngeo. No se requiere en todos los casos, pero es completamente para la nasofaringoscopía. La videograbación no es indispensable. Siempre se deben realizar las incidencias frontal, lateral y basal

Cambios foniátricos en niños de tres a cinco años por pérdida prematura de los incisivos superiores / Phoniatric alterations in children between 3 and 5 years, with premature loss of the upper incisors

Introducción. El propósito de este estudio fue detectar los cambios foniátricos que suceden a la pérdida prematura de los incisivos superiores. Material y Métodos. El grupo experimental se formó por 20 niños sanos de 3-5 años, independientemente del sexo y con un periodo de tres meses a un año de haber perdido los cuatro incisivos superiores. El grupo testigo estuvo formado por 20 niños sanos de 3-5 años de edad, independientemente del sexo y con integridad de los cuatro incisivos superiores. Ambos grupos fueron evaluados por un especialista en foniatría mediante la prueba de CEFI (Cuestionario de evaluación fonológica infantil). Resultados. Los pacientes con pérdida prematura de los incisivos superiores presentaron dislalia en un 67%(6) del grupo de mujeres y 100%(14) de hombres, mientras que el grupo control presentó dislalia en un 46%(8) de mujeres y 54%(12) de hombres. Conclusiones. Aunque en ambos grupos se presentaron más hombres que mujeres, al analizar la incidencia de casos con dislalia por medio de X2, los varones muestran mayor número de alteraciones. La pérdida prematura de los cuatro incisivos superiores es un factor predisponente para la presentación de dislalia. El tiempo que transcurre después de esta pérdida es proporcionalmente directo a la gravedad del problema foniátrico