Infectious and Noninfectious Corneal Ulcers in Ocular Graft-Versus-Host Disease: Epidemiology, Clinical Characteristics, and Outcomes.

PURPOSE: To evaluate the incidence, clinical characteristics, microbiological profile, and therapeutic outcomes of corneal ulcers in individuals with chronic ocular graft-vs-host disease (coGVHD). DESIGN: Retrospective clinical cohort study. METHODS: Review of individuals diagnosed with coGVHD following hematopoietic stem cell transplantation (HSCT) who were seen at the Bascom Palmer Eye Institute between May 2010 and November 2021. Baseline demographics, clinical characteristics, microbiological profile, risk factors for corneal ulceration, and treatment outcomes were collected. Etiology was deemed infectious in individuals with a positive culture or appropriate clinical scenario (presence of stromal infiltrate or hypopyon); otherwise, ulcers were presumed to be noninfectious. Treatment success was defined as reepithelialization with infiltrate resolution, and treatment failure as progression to corneal perforation or keratoplasty. Kaplan-Meier survival analysis estimated the incidence of ulceration. Cox regression analyses examined demographic and risk factors. Infectious and noninfectious ulcer groups were compared using 2-way independent t tests, 1-way analysis of variances, and χ2 tests, as appropriate. RESULTS: 173 individuals were included (53.7±14.4 years old; 59.0% male). Thirty-three individuals developed an ulcer 74.5±54.3 months after HSCT, with estimated 5- and 10-year incidences of 14% and 30%, respectively. Twenty-two (66.6%) ulcers were deemed infectious (15 microbiologically confirmed, 7 clinically) and 11 (33.3%) were deemed noninfectious. Risk factors for corneal ulceration included Black race (hazards ratio [HR] 2.89, 95% CI 1.30-6.42, P < .01), previous ocular surgery (HR 9.16, 95% CI 3.86-21.72, P < .01), eyelid margin abnormalities (HR 3.44, 95% CI 1.69-6.99, P < .01), and topical steroid use (HR 2.74, 95% CI 1.33-5.62, P < .01). Conversely, contact lens use reduced the risk of corneal ulceration (HR 0.29, 95% CI 0.13-0.66, P < .01). Infectious ulcers had a significantly higher frequency of treatment failure than noninfectious ulcers (57.1% vs 20.0%, P = .04). CONCLUSION: Corneal ulceration is a potential complication of coGVHD, with several clinical features identified as risk factors. Infectious ulcers had worse outcomes than noninfectious ulcers.

Pilot feasibility study of a digital technology approach to the systematic electronic capture of parent-reported data on cognitive and language development in children aged 2 years.

BACKGROUND: The assessment of language and cognition in children at risk of impaired neurodevelopment following neonatal care is a UK standard of care but there is no national, systematic approach for obtaining these data. To overcome these challenges, we developed and evaluated a digital version of a validated parent questionnaire to assess cognitive and language development at age 2 years, the Parent Report of Children's Abilities-Revised (PARCA-R). METHODS: We involved clinicians and parents of babies born very preterm who received care in north-west London neonatal units. We developed a digital version of the PARCA-R questionnaire using standard software. Following informed consent, parents received automated notifications and an invitation to complete the questionnaire on a mobile phone, tablet or computer when their child approached the appropriate age window. Parents could save and print a copy of the results. We evaluated ease of use, parent acceptability, consent for data sharing through integration into a research database and making results available to the clinical team. RESULTS: Clinical staff approached the parents of 41 infants; 38 completed the e-registration form and 30 signed the e-consent. The digital version of the PARCA-R was completed by the parents of 21 of 23 children who reached the appropriate age window. Clinicians and parents found the system easy to use. Only one parent declined permission to integrate data into the National Neonatal Research Database for approved secondary purposes. DISCUSSION: This electronic data collection system and associated automated processes enabled efficient systematic capture of data on language and cognitive development in high-risk children, suitable for national delivery at scale.

Evaluation of freely available data profiling tools for health data research application: a functional evaluation review.

OBJECTIVES: To objectively evaluate freely available data profiling software tools using healthcare data. DESIGN: Data profiling tools were evaluated for their capabilities using publicly available information and data sheets. From initial assessment, several underwent further detailed evaluation for application on healthcare data using a synthetic dataset of 1000 patients and associated data using a common health data model, and tools scored based on their functionality with this dataset. SETTING: Improving the quality of healthcare data for research use is a priority. Profiling tools can assist by evaluating datasets across a range of quality dimensions. Several freely available software packages with profiling capabilities are available but healthcare organisations often have limited data engineering capability and expertise. PARTICIPANTS: 28 profiling tools, 8 undergoing evaluation on synthetic dataset of 1000 patients. RESULTS: Of 28 potential profiling tools initially identified, 8 showed high potential for applicability with healthcare datasets based on available documentation, of which two performed consistently well for these purposes across multiple tasks including determination of completeness, consistency, uniqueness, validity, accuracy and provision of distribution metrics. CONCLUSIONS: Numerous freely available profiling tools are serviceable for potential use with health datasets, of which at least two demonstrated high performance across a range of technical data quality dimensions based on testing with synthetic health dataset and common data model. The appropriate tool choice depends on factors including underlying organisational infrastructure, level of data engineering and coding expertise, but there are freely available tools helping profile health datasets for research use and inform curation activity.

Retention on antiretroviral therapy during Universal Test and Treat implementation in Zomba district, Malawi: a retrospective cohort study.

INTRODUCTION: Since June 2016, the national HIV programme in Malawi has adopted Universal Test and Treat (UTT) guidelines requiring that all persons who test HIV positive will be referred to start antiretroviral therapy (ART). Although there is strong evidence from clinical trials that early initiation of ART leads to reduced morbidity and mortality, the impact of UTT on retention on ART in real-life programmatic settings in Africa is not yet known. METHODS: We conducted a retrospective cohort study in Zomba district, Malawi to compare ART outcomes of patients who initiated ART under 2016 UTT guidelines and those who started ART prior to rollout of UTT (pre-UTT). We analysed data from 32 rural and urban health facilities of various sizes. Cox proportional hazards modelling was used to determine the independent risk factors of attrition from ART at 12 months. All analyses were adjusted for clustering by health facility using a robust standard errors approach. RESULTS: Among 1492 patients (mean age 34.4 years, 933 (63%) female) who initiated ART during the study period, 501 were enrolled in the pre-UTT cohort and 911 during UTT. At 12 months, retention on ART in the UTT cohort was higher than in the pre-UTT cohort 83.0% (95% confidence interval (CI): 81.0% to 85.0%) versus 76.2% (95% CI 73.9% to 78.5%). Adolescents, aged 10 to 19 years (adjusted hazard ratio (aHR) 1.53; 95% CI 1.01 to 2.32), and women who were pregnant or breastfeeding at ART initiation (aHR 1.87; 95% CI 1.30 to 2.38) were at higher risk of attrition in the combined pre-UTT and UTT cohort. CONCLUSIONS: Retention on ART was nearly 6% higher after UTT introduction. Young adults and women who were pregnant or breastfeeding at the start of ART were at increased risk of attrition, emphasizing the need for targeted interventions for these groups to achieve the 90-90-90 UNAIDS targets in the UTT era.

Effect of cardio-metabolic risk factors on all-cause mortality among HIV patients on antiretroviral therapy in Malawi: A prospective cohort study.

BACKGROUND: Cardiovascular disease (CVD) risk among people living with HIV is elevated due to persistent inflammation, hypertension and diabetes comorbidity, lifestyle factors and exposure to antiretroviral therapy (ART). Data from Africa on how CVD risk affects morbidity and mortality among ART patients are lacking. We explored the effect of CVD risk factors and the Framingham Risk Score (FRS) on medium-term ART outcomes. METHODS: A prospective cohort study of standardized ART outcomes (Dead, Alive on ART, stopped ART, Defaulted and Transferred out) was conducted from July 2014-December 2016 among patients on ART at a rural and an urban HIV clinic in Zomba district, Malawi. The primary outcome was Dead. Active defaulter tracing was not done and patients who transferred out and defaulted were excluded from the analysis. At enrolment, hypertension, diabetes and dyslipidemia were diagnosed, lifestyle data collected and the FRS was determined. Cox-regression analysis was used to determine independent risk factors for the outcome Dead. RESULTS: Of 933 patients enrolled, median age was 42 years (IQR: 35-50), 72% were female, 24% had hypertension, 4% had diabetes and 15.8% had elevated total cholesterol. The median follow up time was 2.4 years. Twenty (2.1%) patients died, 50 (5.4%) defaulted, 63 (6.8%) transferred out and 800 (85.7%) were alive on ART care (81.7% urban vs. 89.9% rural). In multivariable survival analysis, male gender (aHR = 3.28; 95%CI: 1.33-8.07, p = 0.01) and total/HDL cholesterol ratio (aHR = 5.77, 95%CI: 1.21-27.32; p = 0.03) were significantly associated with mortality. There was no significant association between mortality and hypertension, body mass index, central obesity, diabetes, FRS, physical inactivity, smoking at enrolment, ART regimen and WHO disease stage. CONCLUSIONS: Medium-term all-cause mortality among ART patients was associated with male gender and elevated total/HDL cholesterol ratio.

Early experiences integrating hypertension and diabetes screening and treatment in a human immunodeficiency virus clinic in Malawi.

Background: Human immunodeficiency virus (HIV) programmes can be leveraged to manage the growing burden of non-communicable diseases (NCDs). Methods: In October 2015, a model of integrated HIV-NCD care was developed at a large HIV clinic in southeast Malawi. Blood pressure was measured in adults at every visit and random blood glucose was determined every 2 y. Uncomplicated antiretroviral therapy (ART)-only care was provided by nurses, integrated HIV-NCD management was provided by clinical officers. Waiting times were assessed using the electronic medical record system. The team met monthly to identify bottlenecks. Results: All (n=6036) adult HIV patients were screened and 765 were diagnosed with hypertension (prevalence 12.7% [95% confidence interval {CI} 11.9-13.5). A total of 2979 adult HIV patients were screened and 25 were diagnosed with diabetes mellitus (prevalence 0.8% [95% CI 0.6-1.2]). The mean duration of ART visits by clinical officers increased from 80.5 to 90 min during the first quarter following HIV-NCD integration but returned to 75 min the following quarter. The mean number of patients seen per day by clinical officers increased from 6 to 11 and for nurses decreased from 92 to 82 in that time period. The robust vertical HIV system made the design of integrated tools demanding. Challenges of integrated HIV-NCD care were related to patient flow, waiting times, NCD drug availability, data collection, clinic workload and the timing of diabetes and hypertension screening. Conclusions: Integrated HIV-NCD services provision was feasible in our clinic.

Early experiences in integrating cervical cancer screening and treatment into HIV services in Zomba Central Hospital, Malawi.

Background: Malawi has the highest rate of cervical cancer globally and cervical cancer is six to eight times more common in women with HIV. HIV programmes provide an ideal setting to integrate cervical cancer screening. Methods: Tisungane HIV clinic at Zomba Central Hospital has around 3,700 adult women receiving treatment. In October 2015, a model of integrated cervical cancer screening using visual inspection with acetic acid (VIA) was adopted. All women aged 20 and above in the HIV clinic were asked if they had cervical cancer screening in the past three years and, if not, were referred for screening. Screening was done daily by nurses in a room adjacent to the HIV clinic. Cold coagulation was used to treat pre-cancerous lesions. From October 2016, a modification to the HIV programme's electronic medical record was developed that assisted in matching numbers of women sent for screening with daily screening capacity and alerted providers to women with pre-cancerous lesions who missed referrals or treatment. Results: Between May 2016 and March 2017, cervical cancer screening was performed in 957 women from the HIV clinic. Of the 686 (71%) women who underwent first ever screening, 23 (3.4%) were found to have VIA positive lesions suggestive of pre-cancer, of whom 8 (35%) had a same-day cold coagulation procedure, seven (30%) deferred cold coagulation to a later date (of whom 4 came for treatment), and 8 (35%) were referred to surgery due to size of lesion; 5/686 (0.7%) women had lesions suspicious of cancer. Conclusion: Incorporating cervical cancer screening into services at HIV clinics is feasible. A structured approach to screening in the HIV clinic was important.

Greater retention in care among adolescents on antiretroviral treatment accessing "Teen Club" an adolescent-centred differentiated care model compared with standard of care: a nested case-control study at a tertiary referral hospital in Malawi.

INTRODUCTION: There are numerous barriers to the care and support of adolescents living with HIV (ALHIV) that makes this population particularly vulnerable to attrition from care, poor adherence and virological failure. In 2010, a Teen Club was established in Zomba Central Hospital (ZCH), Malawi, a tertiary referral HIV clinic. Teen Club provides ALHIV on antiretroviral treatment (ART) with dedicated clinic time, sexual and reproductive health education, peer mentorship, ART refill and support for positive living and treatment adherence. The purpose of this study was to evaluate whether attending Teen Club improves retention in ART care. METHODS: We conducted a nested case-control study with stratified selection, using programmatic data from 2004 to 2015. Cases (ALHIV not retained in care) and controls (ALHIV retained in care) were matched by ART initiation age group. Patient records were reviewed retrospectively and subjects were followed starting in March 2010, the month in which Teen Club was opened. Follow-up ended at the time patients were no longer considered retained in care or on 31 December 2015. Cases and controls were drawn from a study population of 617 ALHIV. Of those, 302 (48.9%) participated in at least two Teen Club sessions. From the study population, 135 (non-retained) cases and 405 (retained) controls were selected. RESULTS: In multivariable analyses, Teen Club exposure, age at the time of selection and year of ART initiation were independently associated with attrition. ALHIV with no Teen Club exposure were less likely to be retained than those with Teen Club exposure (adjusted odds ratio (aOR) 0.27; 95% CI 0.16, 0.45) when adjusted for sex, ART initiation age, current age, reason for ART initiation and year of ART initiation. ALHIV in the age group 15 to 19 were more likely to have attrition from care than ALHIV in the age group 10 to 14 years of age (aOR 2.14; 95% CI 1.12, 4.11). CONCLUSIONS: This study contributes to the limited evidence evaluating the effectiveness of service delivery interventions to support ALHIV within healthcare settings. Prospective evaluation of the Teen Club package with higher methodological quality is required for programmes and governments in low- and middle-income settings to prioritize interventions for ALHIV and determine their cost-effectiveness.