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BACKGROUND: The COVID-19 pandemic prompted strict public health measures to reduce SARS-CoV-2 transmission, potentially interrupting TB programmes in the Western Cape, South Africa. METHODS: We conducted a retrospective cohort study, estimating changes in new TB case rates and risk of death during TB-specific admissions within 6 months of TB first evidence, during the pre-pandemic (1 January 2019-26 March 2020) and after the implementation of public health and social measures (PHSM) periods (26 March 2020-30 September 2021), based on PHSM strictness. We used interrupted time series and logistic regression models to adjust for key characteristics. RESULTS: We found an average 22% reduction (95% CI 19-25) in monthly TB cases during the entire PHSM implementation period. Additionally, the risk of death during TB-specific admissions increased, with the adjusted odds ratio ranging across PHSM levels from 1.36 (95% CI 1.17-1.57) on Level 1 to 1.44 (95% CI 1.16-1.79) on Level 2 compared with the pre-pandemic period. CONCLUSIONS: There was a decline in the number of diagnosed TB cases and an increased risk of severe outcomes from 26 March 2020 to 30 September 2021 in the Western Cape. TB programme recovery strategies must be prioritised, and TB management programmes must be integrated into future pandemic responses.
CONTEXTE: La pandémie de COVID-19 a entraîné la mise en place de mesures de santé publique strictes afin de limiter la propagation du SRAS-CoV-2, ce qui risque de perturber les efforts de lutte contre la TB dans la province du Cap-Occidental, en Afrique du Sud. MÉTHODES: Une étude de cohorte rétrospective a été réalisée afin d'évaluer les variations des taux de nouveaux cas de TB et le risque de décès lors des admissions spécifiques à la TB dans les 6 mois suivant la première preuve de la maladie. Cette étude a été menée pendant deux périodes distinctes : la période prépandémique, allant du 1er janvier 2019 au 26 mars 2020, et la période post-mise en Åuvre des mesures de santé publique et sociales (PHSM, pour l'anglais « public health and social measures ¼), allant du 26 mars 2020 au 30 septembre 2021. L'objectif était d'évaluer l'impact des PHSM sur ces indicateurs. Pour ce faire, des séries temporelles interrompues et des modèles de régression logistique ont été utilisés afin de prendre en compte les principales caractéristiques. RÉSULTATS: Au cours de la période de mise en Åuvre des PHSM, nous avons observé une diminution moyenne de 22% (IC à 95% 1925) des cas mensuels de TB. De plus, nous avons constaté une augmentation du risque de décès pendant les admissions pour TB, avec un rapport de cotes ajusté variant de 1,36 (IC à 95% ; 1,171,57) au niveau 1 des PHSM à 1,44 (IC à 95% ; 1,161,79) au niveau 2, par rapport à la période prépandémique. CONCLUSIONS: Entre le 26 mars 2020 et le 30 septembre 2021, il y a eu une baisse du nombre de cas de TB diagnostiqués dans la province du Cap-Occidental, mais le risque de résultats graves a augmenté pendant cette période. Les stratégies de rétablissement des programmes de lutte contre la TB doivent être prioritaires et les programmes de gestion de la TB doivent être intégrés dans les futures réponses à la pandémie.
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BACKGROUND: The COVID-19 pandemic resulted in the implementation of strict public health and social measures (PHSMs) (including mobility restrictions, social distancing, mask-wearing and hand hygiene), limitations on non-essential healthcare services, and public fear of COVID-19 infection, all of which potentially affected transmission and healthcare use for other diseases such as lower respiratory tract infections (LRTIs). OBJECTIVE: To determine changes in LRTI hospital admissions and in-facility mortality in children aged <5 years in the Western Cape Province during the pandemic. METHODS: We conducted a retrospective analysis of LRTI admissions and in-facility deaths from January 2019 to November 2021. We estimated changes in rates and trends of LRTI admissions during the pandemic compared with pre-pandemic period using interrupted time series analysis, adjusting for key characteristics. RESULTS: There were 36 277 children admitted for LRTIs during the study period, of whom 58% were male and 51% were aged 28 days - 1 year. COVID-19 restrictions were associated with a 13% step reduction in LRTI admissions compared with the pre-COVID-19 period (incidence rate ratio (IRR) 0.87, 95% confidence interval (CI)) 0.80 - 0.94). The average LRTI admission trend increased on average by 2% per month during the pandemic (IRR 1.02, 95% CI 1.02 - 1.04). CONCLUSIONS: The COVID-19 surges and their associated measures were linked to declining LRTI admissions and in-facility deaths, likely driven by a combination of reduced infectious disease transmission and reduced use of healthcare services, with effects diminishing over time. These findings may inform future pandemic response policies.
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COVID-19 , Infecções Respiratórias , Criança , Humanos , Masculino , Pré-Escolar , Feminino , Pandemias , Estudos Retrospectivos , África do Sul/epidemiologia , Setor Público , Infecções Respiratórias/epidemiologiaRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. RESULTS: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. CONCLUSIONS: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.
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Leucemia Linfocítica Crônica de Células B , Melanoma , Adulto , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Austrália , Melanoma/patologia , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
BACKGROUND: Routinely collected population-wide health data are often used to understand mortality trends including child mortality, as these data are often available more readily or quickly and for lower geographic levels than population-wide mortality data. However, understanding the completeness and accuracy of routine health data sources is essential for their appropriate interpretation and use. This study aims to assess the accuracy of diagnostic coding for public sector in-facility childhood (age < 5 years) infectious disease deaths (lower respiratory tract infections [LRTI], diarrhoea, meningitis, and tuberculous meningitis [TBM]) in routine hospital information systems (RHIS) through comparison with causes of death identified in a child death audit system (Child Healthcare Problem Identification Programme [Child PIP]) and the vital registration system (Death Notification [DN] Surveillance) in the Western Cape, South Africa and to calculate admission mortality rates (number of deaths in admitted patients per 1000 live births) using the best available data from all sources. METHODS: The three data sources: RHIS, Child PIP, and DN Surveillance are integrated and linked by the Western Cape Provincial Health Data Centre using a unique patient identifier. We calculated the deduplicated total number of infectious disease deaths and estimated admission mortality rates using all three data sources. We determined the completeness of Child PIP and DN Surveillance in identifying deaths recorded in RHIS and the level of agreement for causes of death between data sources. RESULTS: Completeness of recorded in-facility infectious disease deaths in Child PIP (23/05/2007-08/02/2021) and DN Surveillance (2010-2013) was 70% and 69% respectively. The greatest agreement in infectious causes of death were for diarrhoea and LRTI: 92% and 84% respectively between RHIS and Child PIP, and 98% and 83% respectively between RHIS and DN Surveillance. In-facility infectious disease admission mortality rates decreased significantly for the province: 1.60 (95% CI: 1.37-1.85) to 0.73 (95% CI: 0.56-0.93) deaths per 1000 live births from 2007 to 2020. CONCLUSION: RHIS had accurate causes of death amongst children dying from infectious diseases, particularly for diarrhoea and LRTI, with declining in-facility admission mortality rates over time. We recommend integrating data sources to ensure the most accurate assessment of child deaths.
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Doenças Transmissíveis , Infecções Respiratórias , Criança , Humanos , Lactente , Pré-Escolar , Causas de Morte , África do Sul/epidemiologia , Fonte de Informação , Setor Público , DiarreiaRESUMO
BACKGROUND: Antimicrobial resistance (AMR) is a growing problem worldwide. With the current occurrence of pan-resistant bacterial infections and a paucity of novel antimicrobials in development, the world has entered a post-antibiotic era, in which previously treatable, common infections can become fatal. Antimicrobial stewardship (AMS), defined as 'co-ordinated interventions to ensure appropriate and rational use of antimicrobials', aims to decrease rates of AMR. OBJECTIVES: To co-ordinate AMS in Western Cape Province. The National Department of Health (NDoH) has identified AMS as a key strategic objective, and the Western Cape has formed a provincial AMS committee. However, not much is known regarding current AMS activities in health facilities in the province. METHODS: A self-administered, email questionnaire was sent to specific staff at all district, regional and tertiary hospitals in the 6 health districts of the Western Cape - 47 facilities in total, of which 35 (74.4%) responded. Respondents included pharmacists, managers, doctors, nurses, infection prevention and control practitioners, as well as quality assurance practitioners. The number of facilities implementing AMS were determined, as well as the composition of AMS committees and the nature and frequency of team activities. Barriers to facility-level AMS were explored. Support and outreach activities were assessed, as well as facilities' needs and expectations of the provincial AMS committee. RESULTS: Approximately half of all responding hospitals (n=19; 54.3%) had active AMS committees. Double the proportion of metropolitan (83.3%) than rural facilities (39.1%) had committees. Stewardship activities included antimicrobial prescription chart reviews and audits, AMS ward rounds, antimicrobial restriction policies and training. Most committees included a pharmacist and an infection prevention and control practitioner. More than a third of hospitals (36.1%) did not review their antimicrobial consumption data on a regular basis. Just over half of the hospitals (n=18; 51.4%) did not review AMR patterns. CONCLUSIONS: Despite the need for effective AMS, there is limited information on AMS in South Africa. Most assistance is required in rural areas and smaller hospitals with low numbers of staff and greater numbers of transient rotating junior staff. Information management support, multidisciplinary teamwork and clinical governance are required to enable regular and ongoing AMS in facilities. Rural and smaller facilities require greater support to establish effectively functioning AMS committees.
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Anti-Infecciosos/administração & dosagem , Gestão de Antimicrobianos/estatística & dados numéricos , Recursos Humanos em Hospital/estatística & dados numéricos , Gestão de Antimicrobianos/organização & administração , Hospitais/estatística & dados numéricos , Humanos , Equipe de Assistência ao Paciente/organização & administração , Farmacêuticos/organização & administração , África do Sul , Inquéritos e QuestionáriosRESUMO
Access to COVID-19 vaccines has raised concerns globally. Despite calls for solidarity and social justice during the pandemic, vaccine nationalism, stockpiling of limited vaccine supplies by high-income countries and profit-driven strategies of global pharmaceutical manufacturers have brought into sharp focus global health inequities and the plight of low- and middle-income countries (LMICs) as they wait in line for restricted tranches of vaccines. Even in high-income countries that received vaccine supplies first, vaccine roll-out globally has been fraught with logistic and ethical challenges. South Africa (SA) is no exception. Flawed global institutional strategies for vaccine distribution and delivery have undermined public procurement platforms, leaving LMICs facing disproportionate shortages necessitating strict criteria for vaccine prioritisation. In anticipation of our first consignment of vaccines, deliberations around phase 1 roll-out were intense and contentious. Although the first phase focuses on healthcare personnel (HCP), the devil is in the detail. Navigating the granularity of prioritising different categories of risk in healthcare sectors in SA is complicated by definitions of risk in personal and occupational contexts. The inequitable public-private divide that characterises the SA health system adds another layer of complexity. Unlike other therapeutic or preventive interventions that are procured independently by the private health sector, COVID-19 vaccine procurement is currently limited to the SA government only, leaving HCP in the private sector dependent on central government allocation. Fair distribution among tertiary, secondary and primary levels of care is another consideration. Taking all these complexities into account, procedural and substantive ethical principles supporting a prioritisation approach are outlined. Within the constraints of suboptimal global health governance, LMICs must optimise progressive distribution of scarce vaccines to HCP at highest risk.
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Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Saúde Global , Acessibilidade aos Serviços de Saúde/ética , Vacinas contra COVID-19/provisão & distribuição , Países em Desenvolvimento , Pessoal de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde , Humanos , Setor Privado , Setor Público , Justiça Social , África do SulRESUMO
Asymptomatic COVID-19 may contribute significantly to the pandemic trajectory based on global biological, epidemiological and modelling evidence. A retrospective analysis was done to determine the proportion of asymptomatic COVID-19 in the workplace during the lockdown period from 27 March to 31 May 2020. We found that nearly 45% of cases were asymptomatic at the time of the first test. This high proportion of asymptomatic COVID-19 cases has implications for interventions, such as enforcing quarantine of all close contacts of COVID-19 cases regardless of symptoms.
Le COVID-19 a symptomatique pourrait contribuer significativement à la trajectoire de la pandémie en se basant sur des preuves mondiales, biologique et épidémiologiques, et en modélisant les preuves. Une analyse rétrospective a été réalisée afin de décrire la proportion d'infections asymptomatiques de SARS-CoV-2 parmi les clusters essentiels sur les lieux de travail en Afrique du Sud où des investigations de flambée ont été réalisées durant la période de confinement très restrictive du 27 mars au 31 mai 2020. Près de 45% des cas étaient asymptomatique lors du premier test. Cette proportion élevée des cas de COVID-19 asymptomatiques a des implications en ce qui concerne les interventions nonpharmaceutique comme le renforcement de la quarantaine de tous les contacts étroits des cas de SARS-CoV-2 sans tenir compte des symptômes.
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AIMS: Mental disorders are common in people living with HIV (PLWH) but often remain untreated. This study aimed to explore the treatment gap for mental disorders in adults followed-up in antiretroviral therapy (ART) programmes in South Africa and disparities between ART programmes regarding the provision of mental health services. METHODS: We conducted a cohort study using ART programme data and linked pharmacy and hospitalisation data to examine the 12-month prevalence of treatment for mental disorders and factors associated with the rate of treatment for mental disorders among adults, aged 15-49 years, followed-up from 1 January 2012 to 31 December 2017 at one private care, one public tertiary care and two pubic primary care ART programmes in South Africa. We calculated the treatment gap for mental disorders as the discrepancy between the 12-month prevalence of mental disorders in PLWH (aged 15-49 years) in South Africa (estimated based on data from the Global Burden of Disease study) and the 12-month prevalence of treatment for mental disorders in ART programmes. We calculated adjusted rate ratios (aRRs) for factors associated with the treatment rate of mental disorders using Poisson regression. RESULTS: In total, 182 285 ART patients were followed-up over 405 153 person-years. In 2017, the estimated treatment gap for mental disorders was 40.5% (95% confidence interval [CI] 19.5-52.9) for patients followed-up in private care, 96.5% (95% CI 95.0-97.5) for patients followed-up in public primary care and 65.0% (95% CI 36.5-85.1) for patients followed-up in public tertiary care ART programmes. Rates of treatment with antidepressants, anxiolytics and antipsychotics were 17 (aRR 0.06, 95% CI 0.06-0.07), 50 (aRR 0.02, 95% CI 0.01-0.03) and 2.6 (aRR 0.39, 95% CI 0.35-0.43) times lower in public primary care programmes than in the private sector programmes. CONCLUSIONS: There is a large treatment gap for mental disorders in PLWH in South Africa and substantial disparities in access to mental health services between patients receiving ART in the public vs the private sector. In the public sector and especially in public primary care, PLWH with common mental disorders remain mostly untreated.
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Infecções por HIV , Transtornos Mentais , Adolescente , Adulto , Estudos de Coortes , Registros Eletrônicos de Saúde , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , África do Sul/epidemiologia , Adulto JovemRESUMO
BACKGROUND: HIV-serodiscordant couples are at high risk of HIV transmission. In sub-Saharan Africa, HIV-serodiscordant couples contribute ~30% of all new infections in the region. OBJECTIVES: To quantify the prevalence of HIV-serodiscordant couples and evaluate steps of the HIV cascade of care among people living with HIV in serodiscordant relationships in four high-prevalence settings in sub-Saharan Africa. METHODS: Four HIV prevalence surveys were conducted: in Ndhiwa (Kenya) in 2012, in Chiradzulu (Malawi) in 2013, and in Gutu (Zimbabwe) and Nsanje (Malawi) in 2016. Eligible individuals aged 15 - 59 years were asked to participate in voluntary rapid HIV testing. Viral load and CD4 counts were measured on those who tested HIV-positive. A couple was defined as a man and a woman who reported being married or cohabiting and were living together in the same household. RESULTS: Among 4 385 couples, the prevalence of HIV serodiscordancy was 10.9% (95% confidence interval (CI) 10.2 - 11.5) overall, ranging from 6.7% (95% CI 5.6 - 7.9) in Nsanje to 15.8% (95% CI 14.5 - 17.3) in Ndhiwa. Men were the HIV-positive partner in 62.7% of the serodiscordant couples in Ndhiwa, in 60.4% in Gutu, in 48.8% in Chiradzulu and in 50.9% in Nsanje. Status awareness among HIV-positive partners in serodiscordant couples ranged from 45.4% in Ndhiwa to 70.7% in Gutu. Viral load suppression (VLS) ranged from 33.9% in Ndhiwa to 68.5% in Nsanje. VLS was similar by sex in three settings, Ndhiwa (37.8% (men) v. 27.8% (women); p=0.16), Nsanje (60.7% v. 76.9%; p=0.21) and Gutu (48.2% v. 55.6%; p=0.63), and dissimilar by sex in Chiradzulu (44.4% v. 62.7%; p=0.03). CONCLUSIONS: Low HIV status awareness and poor VLS among HIV-positive partners are major gaps in preventing transmission among serodiscordant couples. Intensifying programmes that target couples to test for HIV and timely antiretroviral therapy initiation could increase VLS and reduce HIV transmission.
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Infecções por HIV/psicologia , Parceiros Sexuais/psicologia , Adolescente , Adulto , Estudos Transversais , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Quênia/epidemiologia , Malaui/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Carga ViralRESUMO
BACKGROUND: Recent clinical trials demonstrated the safety and efficacy of neoadjuvant dabrafenib and trametinib (DT) among patients with surgically resectable clinical stage III BRAFV600E/K mutant melanoma. Although patients achieving a complete pathological response (pCR) exhibited superior recurrence-free survival (RFS) versus those who did not, 30% of pCR patients relapsed. We sought to identify whether histopathological features of the pathological response further delineated risk of relapse. METHODS: Surgical resection specimens from DT-treated patients in two phase 2 clinical trials were reviewed. Histopathological features, including relative amounts of viable tumour, necrosis, melanosis, and fibrosis (hyalinized or immature/proliferative) were assessed for associations with patient outcomes. RESULTS: Fifty-nine patients underwent surgical resection following neoadjuvant DT. Patients achieving pCR (49%) had longer RFS compared with patients who did not (P = 0.005). Patients whose treated tumour showed any hyalinized fibrosis had longer RFS versus those without (P = 0.014), whereas necrosis (P = 0.012) and/or immature/proliferative fibrosis (P = 0.026) correlated with shorter RFS. Multivariable analyses showed absence of pCR or presence of immature fibrosis independently predicted shorter RFS. Among pCR patients, mature/hyalinized-type fibrosis correlated with improved RFS (P = 0.035). CONCLUSIONS: The extent and composition of the pathological response following neoadjuvant DT in BRAFV600E/K mutant melanoma correlates with RFS, including pCR patients. These findings support the need for detailed histological analysis of specimens collected after neoadjuvant therapy.
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Melanoma , Segunda Neoplasia Primária , Neoplasias Cutâneas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Humanos , Melanoma/tratamento farmacológico , Melanoma/genética , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Resultado do TratamentoRESUMO
BACKGROUND: Injury remains a leading cause of childhood morbidity and mortality in the developing world. The probability of injury occurrence is influenced by agent, host and environmental factors. Studies of repeat injuries in childhood therefore provide insight into factors in the epidemiological triad predisposing children to injury. OBJECTIVES: To determine the proportion of children and the factors associated with repeat presentations to the Red Cross War Memorial Children's Hospital Trauma Unit (RCWMCH TU) in Cape Town, South Africa, for all non-transport-related injuries in childhood. METHODS: This was a retrospective cohort study using data from the RCWMCH TU. We included children aged 0 - 10 years with first presentation from January 1997 to June 2013 and followed up until the earlier of age 13 years or June 2016. We assessed individual and population-level factors associated with repeat injury using multilevel Poisson regression analysis. Child dependency ratios were derived from the 2011 National Census. RESULTS: Between 1997 and 2013, 72 490 children aged <10 years (59% male) presented to the RCWMCH TU for the first time with injuries. After the initial injury, 9 417 (13%) presented with a repeat injury by 2016 and before age 13 years. After adjusting for health subdistrict, distance from RCWMCH TU and age at first presentation, factors associated with reduced repeat presentation were injury identified as due to abuse (adjusted incidence rate ratio (aIRR) 0.6; 95% confidence interval (CI) 0.4 - 0.7), fluid burn (aIRR 0.6; 95% CI 0.6 - 0.7), foreign body ingestion (aIRR 0.7; 95% CI 0.7 - 0.9), and moderate and severe (v. minor) initial injury (aIRR 0.9; 95% CI 0.8 - 0.9 and aIRR 0.7; 95% CI 0.6 - 0.8, respectively), while boys were more likely to have repeat injury presentations (aIRR 1.4; 95% CI 1.4 - 1.5). CONCLUSIONS: Repeat presentations were substantial and associated with male gender. They occurred less commonly after fluid burn injuries, foreign body ingestion and moderate to severe injuries. Children with intentional injuries were also less likely to have a repeat presentation. Further research is indicated for childhood injuries with greater propensity to repeat, including non-height falls and sport-related injuries. Secondary injury prevention education should not neglect patients with unintentional and minor injuries. These results strengthen the hypothesis that injuries arise as a result of sustained exposure to agent, host and environmental risk factors.
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Queimaduras/epidemiologia , Maus-Tratos Infantis/estatística & dados numéricos , Corpos Estranhos/epidemiologia , Relesões/epidemiologia , Ferimentos e Lesões/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hospitais Pediátricos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , África do Sul/epidemiologia , Centros de TraumatologiaRESUMO
Longitudinal targeted maximum likelihood estimation (LTMLE) has very rarely been used to estimate dynamic treatment effects in the context of time-dependent confounding affected by prior treatment when faced with long follow-up times, multiple time-varying confounders, and complex associational relationships simultaneously. Reasons for this include the potential computational burden, technical challenges, restricted modeling options for long follow-up times, and limited practical guidance in the literature. However, LTMLE has desirable asymptotic properties, ie, it is doubly robust, and can yield valid inference when used in conjunction with machine learning. It also has the advantage of easy-to-calculate analytic standard errors in contrast to the g-formula, which requires bootstrapping. We use a topical and sophisticated question from HIV treatment research to show that LTMLE can be used successfully in complex realistic settings, and we compare results to competing estimators. Our example illustrates the following practical challenges common to many epidemiological studies: (1) long follow-up time (30 months); (2) gradually declining sample size; (3) limited support for some intervention rules of interest; (4) a high-dimensional set of potential adjustment variables, increasing both the need and the challenge of integrating appropriate machine learning methods; and (5) consideration of collider bias. Our analyses, as well as simulations, shed new light on the application of LTMLE in complex and realistic settings: We show that (1) LTMLE can yield stable and good estimates, even when confronted with small samples and limited modeling options; (2) machine learning utilized with a small set of simple learners (if more complex ones cannot be fitted) can outperform a single, complex model, which is tailored to incorporate prior clinical knowledge; and (3) performance can vary considerably depending on interventions and their support in the data, and therefore critical quality checks should accompany every LTMLE analysis. We provide guidance for the practical application of LTMLE.
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Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Funções Verossimilhança , Causalidade , Criança , Simulação por Computador , Fatores de Confusão Epidemiológicos , Infecções por HIV/epidemiologia , Humanos , Tamanho da AmostraRESUMO
BACKGROUND: The Joint United Nations Programme on HIV/AIDS (UNAIDS) third 90-90-90 target requires 90% of patients on antiretroviral treatment (ART) to be virally suppressed (<1 000 copies/mL). In Khayelitsha, Cape Town, South Africa viral load (VL) suppression of <400 copies/mL was reported as 89% in 2016, but only 56% of patients had a result recorded in routine data. We conceived a VL 'cascade' to represent the steps required for an expected VL to be reported as complete in routine data and thus contribute to reported VL suppression: among those for whom a VL is 'expected', a sample must be collected and tested ('done'), a result must be 'filed' in the patient folder, 'noted' by a clinician and electronically 'captured'. The low reported completion suggested gaps along the VL cascade and cast doubt on the validity of reported suppression. OBJECTIVES: To assess the validity of routinely reported VL suppression and identify barriers to VL completion. METHODS: A retrospective cohort study between 1 July 2015 and 30 June 2016, which included all Khayelitsha patients receiving ART, with a routine VL expected, was conducted. We obtained data routinely captured on site and VL data from the laboratory system. A sample of 1 035 patient folders was reviewed. VL suppression was calculated using laboratory data, including all tests done, and compared with reported suppression based on on-site captured electronic data. Successful progression through each step on the VL cascade was estimated. We used logistic regression to identify factors associated with laboratory data and reported VL testing. RESULTS: Of 22 991 patients for whom a routine VL test was due, 84% were done, 79% filed, 76% noted and 55% captured. Using all laboratory data, VL suppression was estimated as 82%, 87%, 89% and 91% at the 50, 200, 400 and 1 000 copies/mL thresholds, respectively, but reported suppression using captured results was 80%, 86%, 88% and 89% at those thresholds. Routine VL testing is more likely to be done in children <15 years old (adjusted odds ratio (aOR) 1.89, 95% confidence interval (CI) 1.45 - 2.48) and pregnant women (aOR 1.90, 95% CI 1.28 - 2.81) than in men, adjusted for facility. CONCLUSIONS: Despite a low reported completion, VL testing completion was high. Reported suppression using captured data was similar to suppression calculated using all laboratory data, which provided an accurate measure of progress towards the 90-90-90 target. More work is needed to reach the 16% of patients missed by routine testing.
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Fármacos Anti-HIV/uso terapêutico , Monitoramento de Medicamentos/normas , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Carga Viral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Criança , Monitoramento de Medicamentos/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Infecções por HIV/sangue , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Garantia da Qualidade dos Cuidados de Saúde , Reprodutibilidade dos Testes , Estudos Retrospectivos , África do Sul , Resultado do Tratamento , Adulto JovemRESUMO
Background. The Joint United Nations Programme on HIV/AIDS (UNAIDS) third 90-90-90 target requires 90% of patients on antiretroviral treatment (ART) to be virally suppressed (<1 000 copies/mL). In Khayelitsha, Cape Town, South Africa viral load (VL) suppression of <400 copies/mL was reported as 89% in 2016, but only 56% of patients had a result recorded in routine data. We conceived a VL 'cascade' to represent the steps required for an expected VL to be reported as complete in routine data and thus contribute to reported VL suppression: among those for whom a VL is 'expected', a sample must be collected and tested ('done'), a result must be 'filed' in the patient folder, 'noted' by a clinician and electronically 'captured'. The low reported completion suggested gaps along the VL cascade and cast doubt on the validity of reported suppression.Objectives. To assess the validity of routinely reported VL suppression and identify barriers to VL completion. Methods. A retrospective cohort study between 1 July 2015 and 30 June 2016, which included all Khayelitsha patients receiving ART, with a routine VL expected, was conducted. We obtained data routinely captured on site and VL data from the laboratory system. A sample of 1 035 patient folders was reviewed. VL suppression was calculated using laboratory data, including all tests done, and compared with reported suppression based on on-site captured electronic data. Successful progression through each step on the VL cascade was estimated. We used logistic regression to identify factors associated with laboratory data and reported VL testing.Results. Of 22 991 patients for whom a routine VL test was due, 84% were done, 79% filed, 76% noted and 55% captured. Using all laboratory data, VL suppression was estimated as 82%, 87%, 89% and 91% at the 50, 200, 400 and 1 000 copies/mL thresholds, respectively, but reported suppression using captured results was 80%, 86%, 88% and 89% at those thresholds. Routine VL testing is more likely to be done in children <15 years old (adjusted odds ratio (aOR) 1.89, 95% confidence interval (CI) 1.45 - 2.48) and pregnant women (aOR 1.90, 95% CI 1.28 - 2.81) than in men, adjusted for facility. Conclusions. Despite a low reported completion, VL testing completion was high. Reported suppression using captured data was similar to suppression calculated using all laboratory data, which provided an accurate measure of progress towards the 90-90-90 target. More work is needed to reach the 16% of patients missed by routine testing
Assuntos
Antirretrovirais , Estudos de Coortes , Infecções por HIV/terapia , África do Sul , Carga ViralRESUMO
BACKGROUND: Antibiotic resistance (ABR) is a major threat to global health, driven in part by inappropriate prescription of antibiotics in primary care. OBJECTIVES: To describe South African (SA) prescribers' knowledge of, attitudes to and perceptions of ABR. METHODS: We conducted a cross-sectional survey of knowledge of, attitudes to and perceptions of ABR among a convenience sample of primary healthcare providers in SA, the majority from the private sector. We used logistic regression to examine associations between knowledge and prescribing behaviours. RESULTS: Of 264 prescriber respondents, 95.8% (230/240) believed that ABR is a significant problem in SA and 66.5% (157/236) felt pressure from patients to prescribe antibiotics. The median knowledge score was 5/7, and scores were highest in respondents aged <55 years (p=0.0001). Prescribers with higher knowledge scores were more likely than those with lower scores to believe that to decrease ABR, narrow-spectrum antibiotics should be used (adjusted odds ratio (aOR) 1.29, 95% confidence interval (CI) 1 - 1.65) and more likely to report that explaining disease features that should prompt follow-up was a useful alternative to prescribing (aOR 1.47, 95% CI 1.058 - 2.04), and were less likely to report that antibiotics cannot harm the patient if they are not needed, so they prescribe when not necessary (aOR 0.57, 95% CI 0.38 - 0.84). CONCLUSIONS: Prescribers of antibiotics in the private sector in SA were aware of the problem of ABR, but felt pressure from patients to prescribe. Those with higher knowledge scores reported positive prescribing behaviours, suggesting that more education is needed to tackle the problem of ABR.
Assuntos
Antibacterianos/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Adulto , Estudos Transversais , Farmacorresistência Bacteriana , Pesquisas sobre Atenção à Saúde , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Setor Privado , Setor Público , África do SulRESUMO
Background: Clinical trials have recently evaluated safety and efficacy of neoadjuvant therapy among patients with surgically resectable regional melanoma metastases. To capture informative prognostic data connected to pathological response in such trials, it is critical to standardize pathologic assessment and reporting of tumor response after this treatment. Methods: The International Neoadjuvant Melanoma Consortium meetings in 2016 and 2017 assembled pathologists from academic centers to develop consensus guidelines for pathologic examination and reporting of surgical specimens from AJCC (8th edition) stage IIIB/C/D or oligometastatic stage IV melanoma patients treated with neoadjuvant-targeted or immune therapy. Patterns of pathologic response are provided context to inform these guidelines. Results: Based on our collective experience and guided by efforts in well-established neoadjuvant settings like breast cancer, procedures directing handling of pre- and post-neoadjuvant therapy-treated melanoma specimens are provided to facilitate comparison of findings across different trials and centers. Definitions of pathologic response are provided together with guidelines for reporting and quantifying the extent of pathologic response. Finally, the spectrum of histopathologic responses observed following neoadjuvant-targeted and immune-checkpoint therapy is described and illustrated. Conclusions: Standardizing pathologic evaluation of resected melanoma metastases following neoadjuvant-targeted or immune-checkpoint therapy allows more robust stratification of patient outcomes. This includes recognizing the spectrum of histopathologic response patterns to neoadjuvant therapy and a standard approach to grading pathologic responses. Such an approach will facilitate comparison of results across clinical trials and inform ongoing correlative studies into the mechanisms of response and resistance to agents applied in the neoadjuvant setting.
Assuntos
Linfonodos/patologia , Melanoma/terapia , Patologia/normas , Neoplasias Cutâneas/terapia , Pele/patologia , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Biópsia , Ensaios Clínicos como Assunto , Consenso , Procedimentos Cirúrgicos Dermatológicos/métodos , Dermatologia/normas , Humanos , Excisão de Linfonodo/métodos , Linfonodos/efeitos dos fármacos , Linfonodos/cirurgia , Oncologia/normas , Melanoma/patologia , Terapia Neoadjuvante/métodos , Guias de Prática Clínica como Assunto , Prognóstico , Pele/efeitos dos fármacos , Neoplasias Cutâneas/patologia , Manejo de Espécimes/métodos , Manejo de Espécimes/normas , Resultado do TratamentoRESUMO
BACKGROUND: The large scale-up of paediatric HIV care necessitated down-referral of many children receiving antiretroviral therapy (ART) from Red Cross War Memorial Children's Hospital (RCWMCH), Cape Town, South Africa. Few published data exist on the outcomes of these children. OBJECTIVES: To assess outcomes of children receiving ART in the first 12 months after down-referral to primary healthcare (PHC) clinics and identify determinants of successful down-referral. METHODS: A retrospective cohort study of children <15 years of age who initiated ART at RCWMCH and were subsequently down-referred to one of two PHC clinics between January 2006 and December 2012 was completed. Baseline characteristics of patients and caregivers as well as CD4+ counts, viral loads (VLs) and weights were collected 6 and 12 months after down-referral. Outcomes included retention in care and viral suppression. RESULTS: Of 116 children down-referred to the two study PHC clinics, 81.9% arrived at the designated PHC clinic and a further 8.6% continued care at other clinics, the remaining 9.5% being lost to follow-up. Of those successfully down-referred, 11.4% took >8 weeks to present, possibly experiencing treatment interruption. At 12 months after down-referral, only 81.0% remained in care. No factors were associated with retention in care in multivariable analysis. For children who remained in care at the designated PHC clinics, the clinical and immunological gains achieved prior to down-referral were sustained through 12 months of follow-up, and 54.7% of this cohort had documented viral suppression at 12 months. However, if only children with VL results are considered, 75.9% (41/54) were virally suppressed 12 months after down-referral. CONCLUSIONS: Down-referral of children on ART is complex, with risk of loss to follow-up and treatment interruption.
Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV , Administração dos Cuidados ao Paciente , Encaminhamento e Consulta , Adolescente , Criança , Pré-Escolar , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Lactente , Perda de Seguimento , Masculino , Monitorização Imunológica/métodos , Monitorização Imunológica/estatística & dados numéricos , Avaliação de Processos e Resultados em Cuidados de Saúde , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/organização & administração , Administração dos Cuidados ao Paciente/estatística & dados numéricos , Encaminhamento e Consulta/organização & administração , Encaminhamento e Consulta/estatística & dados numéricos , Medição de Risco , Fatores de Risco , África do Sul/epidemiologiaRESUMO
BACKGROUND: The burden of paediatric HIV in South Africa has shifted to older children and adolescents. Nevertheless, information on long-term treatment outcomes of perinatally HIV-infected (PHIV) children is limited. OBJECTIVES: To examine long-term immunological and virological outcomes of children who were in care for at least 10 years after starting antiretroviral therapy (ART). METHODS: We performed a retrospective cohort study of 127 PHIV children who initiated ART at a Cape Town clinic between 2002 and 2005 and were followed up for ≥10 years from the ART initiation date. CD4+ counts and viral loads (VLs) were analysed for each successive year on ART. Treatment history, resistance test results, growth data, hospital admissions and opportunistic infection history were described. RESULTS: The median age at ART initiation was 2.6 years (interquartile range (IQR) 1.3 - 4.9) and the median CD4+ percentage 13.0% (IQR 8.9 - 18.0). The first ART regimen was non-nucleoside reverse transcriptase inhibitor based (63.8%) or protease inhibitor based (36.2%). Median follow-up was 12.2 years (IQR 11.1 - 13.0). At the last assessment, 49.6% of patients were on first-line and 43.3% on second-line ART. At the last assessment, the median CD4+ count was 686 cells/µL (IQR 545 - 859) and 78.7% of children had CD4+ counts >500 cells/µL (92.1% of those on first-line v. 70.9% on second-line ART; p=0.003). At the last assessment, 79.5% of patients were virally suppressed (VL <400 copies/mL), 86.2% of those on first-line v. 76.8% on second-line ART (p=0.183). The 10-year probability of experiencing viral failure (VF) was 56.7% (95% confidence interval (CI) 48.3 - 65.5) and the 10-year probability of switching to second-line ART 45.7% (95% CI 37.5 - 54.8). The probability of experiencing VF between the ages of 10 and 18 years was 37.4% (95% CI 25.4 - 52.8). CONCLUSIONS: Virological and immunological outcomes were good overall in PHIV children who remained in care for ≥10 years at this clinic, but >40% of children were on second-line ART with poorer immunological outcomes.