Matthew P Fox

• DSc Epidemiology
• Professor (Associate) at Boston University

Background In 2019, South Africa’s Antiretroviral Therapy (ART) Treatment Guidelines replaced efavirenz with dolutegravir in first-line ART. Setting We assessed the impact of this national guideline change on retention and viral suppression in the Themba Lethu Clinical Cohort, Johannesburg, South Africa. We applied a regression discontinuity desig...

Introduction: South African young adults are at increased risk for HIV acquisition and other non-communicable diseases and face significant barriers to accessing healthcare services. The rapid development of artificial intelligence (AI), in particular AI-powered healthcare assistants (AIPHA), presents a unique opportunity to increase access to heal...

Background Under South Africa’s Universal Test and Treat (UTT) policy, CD4 counts are no longer required to determine HIV treatment eligibility. However, CD4 count at presentation remains an important marker of disease progression. We assessed whether CD4 testing declined in the UTT era and, if so, by how much. Methods We analysed CD4 count data f...

Background: We previously published a systematic review evaluating retention in care after antiretroviral therapy treatment initiation among adults in low- and middle-income countries. We estimated retention at 36 months to be at 74% for studies published from 2008-2013. This review evaluates retention after the implementation of Universal Test and...

Introduction Occupational injuries have been associated with increased suicide mortality, but prior studies have not accounted for pre‐injury depression. Methods We linked injuries that occurred from 1994 to 2000 in the Washington State workers' compensation system with Social Security Administration data on earnings and mortality through 2018. We...

In 1992, Wacholder and colleagues developed a theoretical framework for case-control studies to minimize bias in control selection. They described three comparability principles (study base, deconfounding, and comparable accuracy) to reduce the potential for selection bias, confounding, and information bias in case-control studies. Wacholder et al....

Introduction Replacing conventional, facility-based HIV treatment with less intensive differentiated service delivery (DSD) models could benefit DSD clients and the health system, but its value depends on maintaining or improving clinical outcomes. We compared retention and viral suppression between antiretroviral therapy (ART) clients enrolled in...

Objectives To estimate the impact of occupational injury and illness on opioid-related mortality while accounting for confounding by preinjury opioid use. Methods We employed a retrospective cohort study design using Washington State workers’ compensation data for 1994–2000 injuries linked to US Social Security Administration earnings and mortalit...

Background Intersectionality, or the multidimensional influence of social identity and systems of power, may drive increased morbidity and mortality for adults of color with Down syndrome. We documented racial and ethnic differences in death and hospitalizations among Medicaid enrolled adults with Down syndrome and assessed interaction of racial–et...

Importance With the advancement in administrative data as a research tool and the reliance on public health insurance for individuals with Down syndrome, population-level trends in Alzheimer dementia in this population are beginning to be understood. Objective To comprehensively describe the epidemiology of Alzheimer dementia in adults with Down s...

In 1965, Sir Austin Bradford Hill articulated nine viewpoints for evaluating whether a body of evidence about the relationship between an exposure and outcome should be interpreted causally. In this commentary, we highlight a selection of the ways in which these viewpoints have had an impact on the field of epidemiology in terms of methods developm...

ART scale-up has reduced HIV mortality in South Africa. However, less is known about trends in hospital-based HIV care, which is costly and may indicate HIV-related morbidity. We assessed trends in hospital-based HIV care using the National Health Laboratory Service (NHLS) National HIV Cohort. Our study included all adults ≥18 years receiving care...

Quality mentoring improves outcomes across career stages, including a sense of belonging, persistence, and productivity. However, the status quo in mentorship culture-including in epidemiology-is an ad hoc approach. This pervasive culture adversely affects individual mentees and the entire scientific research enterprise. Public health disciplines s...

Background The target trial framework was developed as a strategy to design and analyze observational epidemiologic studies with the aim of reducing bias due to analytic decisions. It involves designing a hypothetical randomized trial to answer a question of interest and systematically considering how to use observational data to emulate each trial...

Background Chronic kidney disease (CKD) has emerged as a substantial global health challenge, with a marked rise in associated mortality. However, it often goes undetected until advanced stages, particularly in low-income and middle-income countries such as South Africa. We investigated the prevalence and progression of CKD in South Africa, utilisi...

Background Vulvodynia impacts up to 8% of women by age 40, and these women may have a more compromised immune system than women with no vulvar pain history. Aim Given that psychiatric morbidity is associated with vulvodynia and is known to activate immune inflammatory pathways in the brain and systemically, we sought to determine whether the assoc...

Objective To estimate the relative rate of all-cause mortality amongst those on antiretroviral treatment (ART) with a history of interruptions compared with those with no previous interruptions in care. Design Retrospective cohort study. Methods We used data from four South African cohorts participating in the International epidemiology Databases...

Background Research out of South Africa estimates the total unmet need for care for those with type 2 diabetes mellitus (diabetes) at 80%. We evaluated the care cascade using South Africa’s National Health Laboratory Service (NHLS) database and assessed if HIV infection impacts progression through its stages. Methods The cohort includes patients f...

Background Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa. Methods Data were combined from 11 clinical coho...

Hypertension is a major contributor to global morbidity and mortality. In South Africa, the government has employed a whole systems approach to address the growing burden of non-communicable diseases. We used a novel incident care cascade approach to measure changes in the South African health system’s ability to manage hypertension between 2011 an...

Retention of antiretroviral (ART) patients is a priority for achieving HIV epidemic control in South Africa. While machine-learning methods are being increasingly utilised to identify high risk populations for suboptimal HIV service utilisation, they are limited in terms of explaining relationships between predictors. To further understand these re...

Few studies have evaluated the association between periodontitis and spontaneous abortion (SAB), and all have limitations. We used data from Pregnancy Study Online (PRESTO), a prospective preconception cohort study of 3,444 pregnancy planners (2019-2022). Participants provided self-reported data on periodontitis diagnosis, treatment, and symptoms o...

Background ART scale-up has reduced HIV mortality in South Africa. However, less is known about trends in hospital-based HIV care, which is costly and may indicate HIV-related morbidity. Methods We assessed trends in hospital-based HIV care using a novel database: the National Health Laboratory Service (NHLS) National HIV Cohort. Our study included...

Systematic error from selection bias, uncontrolled confounding, and misclassification is ubiquitous in epidemiologic research but is rarely quantified using quantitative bias analysis (QBA). This gap may in part be due to the lack of readily modifiable software to implement these methods. Our objective is to provide computing code that can be tailo...

Background:Linkage between health databases typically requires identifiers such as patient names and personal identification numbers. We developed and validated a record linkage strategy to combine administrative health databases without the use of patient identifiers, with application to South Africa’s public sector HIV treatment program. Methods:...

Background: Among people who inject drugs, frequent injecting and experiencing withdrawal are associated with facilitating others' first injections. As these factors may reflect an underlying substance use disorder, we investigated whether first-line oral opioid agonist treatment (OAT; methadone or buprenorphine/naloxone) reduces the likelihood th...

Vulvodynia, impacts up to 8% of women by age 40, and is hypothesized to manifest through an altered immune-inflammatory response. To test this hypothesis, we identified all women born in Sweden between 1973-1996 diagnosed with localized provoked vulvodynia (N76.3) and/or vaginismus (N94.2 or F52.5) between 2001 and 2018. We matched each case to two...

Tuberculosis (TB) is a risk factor for chronic obstructive pulmonary disease (COPD), but COPD is also a predictor of TB. The excess life-years lost to COPD caused by TB can potentially be saved by screening for and treating TB infection. The purpose of this study was to examine the number of life-years that could be saved by preventing TB and TB-at...

Background: The integrase strand transfer inhibitor (INSTI) dolutegravir is recommended in World Health Organization guidelines, but is associated with weight gain. We evaluated weight change in patients switching from efavirenz to dolutegravir in first-line antiretroviral therapy (ART) in Johannesburg, South Africa. Methods: We conducted a pros...

BACKGROUND: In 1967, Frederick Lord posed a conundrum that has confused scientists for over 50-years. Subsequently named Lord's 'paradox', the puzzle centres on the observation that two common approach to analyses of 'change' between two time-points can produce radically different results. Approach 1 involves analysing the follow-up minus baseline...

Objective: Low- and middle-income countries are facing a growing burden of noncommunicable diseases (NCDs). Providing HIV treatment may also provide opportunities to increase access to NCD services in under-resourced environments. We sought to investigate whether reported use of antiretroviral therapy (ART) was associated with increased screening,...

Starting in the 2010s, researchers in the experimental social sciences rapidly began to adopt increasingly open and reproducible scientific practices. These practices include publicly sharing deidentified data when possible, sharing analysis code, and preregistering study protocols. Empirical evidence from the social sciences suggests such practice...

Background Most estimates of HIV retention are derived at the clinic level through antiretroviral (ART) patient management systems, which capture ART clinic visit data, yet these cannot account for silent transfers across HIV treatment sites. Patient laboratory monitoring visits may also be observed in routinely collected laboratory data, which inc...

Background Studies of the association between aircraft noise and hypertension are complicated by inadequate control for potential confounders and a lack of longitudinal assessments, and existing evidence is inconclusive. Objectives We evaluated the association between long-term aircraft noise exposure and risk of hypertension among post-menopausal...

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 virolo...

Objectives: To measure the impact of lost-time occupational injuries on all-cause mortality in Washington State and, using the same data elements and study design, to determine whether the estimated impact was similar to previous estimates for New Mexico. Methods: We linked injuries in the Washington workers' compensation system with Social Secu...

Adolescents and young people living with HIV are at risk of disengaging from HIV care at all stages of the care cascade. Differentiated models of care offer simplified HIV-service delivery options in the hope of improving treatment outcomes, including retention on antiretroviral therapy. However, it remains unclear how successful and widespread the...

Starting in the 2010s, researchers in the experimental social sciences rapidly began to adopt more open and reproducible scientific practices. These practices include publicly sharing deidentified data when possible, sharing analysis code, and preregistering study protocols. Empirical evidence from the social sciences suggests such practices are fe...

We estimated the degree to which language used in the high profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases...

Men have higher rates of attrition from antiretroviral therapy (ART) programs than women. In Khayelitsha, a high HIV prevalence area in South Africa, two public sector primary healthcare clinics offer services, including HIV testing and treatment, exclusively to men. We compared attrition from ART care among men initiating ART at these clinics with...

We propose a framework for thinking through the design and conduct of descriptive epidemiologic studies. A well-defined descriptive question aims to quantify and characterize some feature of the health of a population and must clearly state: 1) the target population, characterized by person and place, and anchored in time; 2) the outcome, event, or...

We thank Dr. Hamra for a thoughtful commentary (1) on our article (2). Dr. Hamra eloquently explains the origins of the heuristic that nondifferential misclassification results in bias toward the null and theorizes about why it remains so popular among researchers. He points out that we have known for 20 or 30 years that there are exceptions to thi...

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI) such as those from American football. Our understanding of this association is based on research in autopsied brains since CTE can only be diagnosed postmortem. Such studies are susceptible to selection bias, which needs t...

Nearly every introductory epidemiology course begins with a focus on person, place and time, the key components of descriptive epidemiology. And yet in our experience, introductory epidemiology courses were the last time we spent any significant amount of training time focused on descriptive epidemiology. This gave us the impression that descriptiv...

Simulation methods are a powerful set of tools that can allow researchers to better characterize phenomenon from the real world. As such, the ability to simulate data represents a critical set of skills that epidemiologists should use to better understand epidemiologic concepts and ensure that they have the tools to continue to self-teach even when...

Measurement error is pervasive in epidemiologic research. Epidemiologists often assume that mismeasurement of study variables is non-differential with respect to other analytic variables and then rely on the heuristic that “non-differential misclassification will bias estimates towards the null.” However, there are many exceptions to the heuristic...

Chapter 2 introduced Bayesian inference and alluded to the close relationship between probabilistic bias analysis and Bayesian methods. The probabilistic bias analysis methods that were discussed in Chapters 7–9 can be considered approximately Bayesian methods. That is, inferential results obtained from a probabilistic bias analysis that adjusts fo...

Summary level probabilistic bias analysis uses aggregate data, such as a 2 × 2 table describing the cell counts and cross-tabulating an exposure and an outcome, or the number of observed cases divided by a census estimate of the number at risk describing disease surveillance. Summary level probabilistic bias analysis applies many of the same equati...

The accurate measurement of exposure, disease occurrence, and relevant covariates is generally necessary to estimate causal relations between exposures and outcomes. However, in all epidemiologic research, there exists the opportunity for measurement errors. When the variables being measured are categorical, these errors are referred to as misclass...

The probabilistic bias analyses shown in the previous chapter were conducted using summarized data. As noted, a major limitation of using the summarized data approach is that it is difficult to adjust for other measured confounders for which adjustment may have been made in the conventional analysis. However, probabilistic bias analysis can be cond...

Epidemiologic investigations have a direct impact on all aspects of health. Studies of social, environmental, behavioral, medical, and molecular factors associated with the incidence of disease or disease outcomes lead to interventions aimed at preventing the disease or improving its outcomes. However, biases are commonplace in epidemiologic resear...

Earlier chapters in this text presented methods for simple bias-adjustments (Chapters 4, 5 and 6). These methods yielded bias-adjusted point estimates, but without any accompanying quantitative description of the uncertainty accompanying that estimate. We showed how the impact of uncertainty in the bias parameter could be described by assigning dif...

Simplified drug regimens may improve retention in care for chronic diseases. In April 2013, South Africa adopted a once-daily single-pill HIV treatment regimen as standard-of-care, replacing a multiple-pill regimen. Because the regimens had similar biological efficacy, the shift to single-pill therapy offers a real-world test of the impact of simpl...

Introduction: Youth living with HIV (YLWH) are less likely to initiate antiretroviral therapy (ART) and remain in care than older adults. It is important to identify effective strategies to address the needs of this growing population and prevent attrition from HIV care. Since 2008, two clinics have offered youth-targeted services exclusively to y...

Introduction Older adolescents aged 15–19 years continue to have high rates of loss to follow up (LTFU), and high rates of virologic non-suppression (VNS) compared to younger adolescents and adults. Adolescent females are at risk of pregnancy, which puts those living with HIV at a dual vulnerability. Our study assessed the factors associated with V...

Systematic reviews and meta-analyses are essential for drawing conclusions regarding etiologic associations between exposures or interventions and health outcomes. Observational studies comprise a substantive source of the evidence base. One major threat to their validity is residual confounding, which may occur when component studies adjust for di...

Background: Studies of people who inject drugs (PWID) commonly use questionnaires to determine whether participants are currently, or have recently been, on opioid agonist treatment for opioid use disorder. However, these previously unvalidated self-reported treatment measures may be susceptible to inaccurate reporting. Methods: We linked baseli...

The coronavirus disease 2019 (COVID-19) pandemic thrust the field of public health into the spotlight. For many epidemiologists, biostatisticians, and other public health professionals, this caused the professional aspects of our lives to collide with the personal, as friends and family reached out with concerns and questions. Learning how to navig...

Introduction: Same-day initiation (SDI) of antiretroviral therapy (ART) for HIV consistently increases ART uptake, but concerns remain about higher attrition from care after initiation. We analysed 12-month retention in the SLATE SDI trials. Methods: SLATE I (Simplified Algorithms for Treatment Eligibility I, enrolment 06 March-28 July 2017) and...

Purpose Recent studies have shown increased all-cause mortality among workers following disabling workplace injury. These studies did not account for two potentially important confounders, smoking and obesity. We estimated injury-related mortality accounting for these factors. Methods We followed workers receiving New Mexico workers’ compensation...

Background. Hypertension is a major contributor to global morbidity and mortality. In South Africa, the government has employed a whole systems approach to address the growing burden of non-communicable diseases. We used a novel incident care cascade approach to measure changes in the South African health system's ability to manage hypertension bet...

We aimed to examine the correlates of antiretroviral therapy (ART) deferral to inform ART demand creation and retention interventions for patients diagnosed with HIV during the Universal Test and Treat (UTT) policy in South Africa. We conducted a cohort study enrolling newly diagnosed HIV-positive adults (≥ 18 years), at four primary healthcare cli...

Objective : To determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa. Study Design and Setting : We used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing a...

We estimated the degree to which language used in the high profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases...

Causal graphs provide a key tool for optimizing the validity of causal effect estimates. Although a large literature exists on the mathematical theory underlying the use of causal graphs, less literature exists to aid applied researchers in understanding how best to develop and use causal graphs in their research projects. We sought to understand w...

Background: Hormonal contraceptive use is common among reproductive-aged women, but research evaluating its etiological relationship to vulvodynia remains mixed. We sought to evaluate this association and examine the potential for bias due to care-seeking behavior. Materials and Methods: We conducted a case-control study of women recruited from a l...

Introduction: Same-day initiation (SDI) of antiretroviral therapy (ART) for HIV consistently increases ART uptake, but concerns remain about higher attrition from care after initiation. We analysed twelve-month retention in the SLATE SDI trials. Methods: SLATE I and SLATE II were individually randomized trials at public outpatient clinics in Johann...

In the 1958 paper ``Shall we count the living or the dead'', Mindel C. Sheps proposed a principled solution to the familiar problem of asymmetry of the relative risk. We provide causal models to clarify the scope and limitations of Sheps' line of reasoning, and show that her preferred variant of the relative risk will be stable between patient grou...

The digital world in which we live is changing rapidly. The changing media environment is having a direct impact on traditional forms of communication and knowledge translation in public health and epidemiology. Openly accessible digital media can be used to reach a broader and more diverse audience of trainees, scientists, and the lay public than...

Peter Ehrenkranz and co-authors present a cyclical cascade of care for people with HIV infection, aiming to facilitate assessment of outcomes.

Background Attrition threatens the success of antiretroviral therapy (ART). In this cohort study, we examined outcomes of people living with HIV (PLHIV) lost to follow-up (LTFU) 2014-2017 at ART programs in Southern Africa. Methods We confirmed LTFU (missed appointment for ≥60 or ≥90 days, according to local guidelines) by checking medical records...

Background: Differentiated care has been proposed to improve HIV treatment outcomes. In June 2016, South Africa's National Department of Health in collaboration with researchers began an evaluation of its National Adherence Guidelines for Chronic Diseases (AGL) which was being rolled-out by NDOH to public sector health facilities. Methods: The e...

Background Facility-based, multimonth dispensing of antiretroviral therapy (ART) for HIV could reduce burdens on patients and providers and improve retention in care. We assessed whether 6-monthly ART dispensing was non-inferior to standard of care and 3-monthly ART dispensing. Methods We did a pragmatic, cluster-randomised, unblinded, non-inferio...

Objective: Although some studies document that posttraumatic stress disorder (PTSD) increases suicide risk, other studies have produced the paradoxical finding that PTSD decreases suicide risk. We sought to understand methodologic biases that may explain these paradoxical findings through the use of directed acyclic graphs (DAGs). Method: DAGs are...

Background Quantitative bias analysis (QBA) measures study errors in terms of direction, magnitude and uncertainty. This systematic review aimed to describe how QBA has been applied in epidemiological research in 2006–19. Methods We searched PubMed for English peer-reviewed studies applying QBA to real-data applications. We also included studies c...

Background Despite widespread availability of HIV treatment, patient outcomes differ across facilities. We propose and evaluate an approach to measure quality of HIV care at health facilities in South Africa’s national HIV program using routine laboratory data. Methods and findings Data were extracted from South Africa’s National Health Laboratory...

Quantitative Bias Analysis comprises the tools used to estimate the direction, magnitude, and uncertainty from systematic errors affecting epidemiologic research. Despite the availability of methods and tools, and guidance for good practices, few reports of epidemiologic research incorporate quantitative estimates of bias impacts. The lack of famil...

Introduction In 2016, under its new National Adherence Guidelines (AGL), South Africa formalized an existing model of fast-track HIV treatment initiation counselling (FTIC). Rollout of the AGL included an evaluation study at 24 clinics, with staggered AGL implementation. Using routinely collected data extracted as part of the evaluation study, we e...

Background Mental health symptoms, stress, and low psychosocial resources are associated with preterm delivery. It is unknown if there are groups of women who experience similar patterns of these adverse psychosocial factors during pregnancy and if the risk of preterm delivery differs among these groups. Objective To identify groups of women with...

Introduction: Policies for Universal Test & Treat (UTT) and same-day initiation (SDI) of antiretroviral therapy (ART) were instituted in South Africa in September 2016 and 2017 respectively. However, there is limited evidence on whether these changes have improved patient retention after HIV diagnosis. Methods: We enrolled three cohorts of newly...

Although variables are often measured with error, the impact of measurement error on machine learning predictions is seldom quantified. The purpose of this study was to assess the impact of measurement error on random forest model performance and variable importance. First, we assessed the impact of misclassification (i.e., measurement error of cat...

Background Elevated progesterone on the day of human chorionic gonadotropin (hCG) administration is associated with decreased live birth rates in IVF cycles. The association with adverse pregnancy outcomes is unknown. Objectives Assess the association between serum progesterone on the day of hCG administration and the risk of ischemic placental di...

Misclassification is a pervasive problem in assessing relations between exposures and outcomes. While some attention has been paid to the impact of dependence in measurement error between exposures and outcomes, there is little awareness of the potential impact of dependent error between exposures and covariates, despite the fact that this latter d...

Background In September 2016, South Africa (SA) began implementing the universal-test-and-treat (UTT) policy in hopes of attaining the UNAIDS 90-90-90 targets by 2020. The SA National Department of Health provided a further directive to initiate antiretroviral therapy (ART) on the day of HIV diagnosis in September 2017. We conducted a qualitative s...