Does type of antiretroviral therapy pick-up point influence 12-month virologic suppression in South Africa?

We assessed the impact of community- versus clinic-based medication pick-up on rates of virologic suppression in an observational cohort of adults on ART enrolled in a decentralized antiretroviral therapy program (CCMDD) in South Africa. Participants either attended clinics where they were given the choice to pick up ART in community venues or traditional clinics, or clinics where this pathway was assigned. Among 1856 participants, 977 (53%) opted for community ART pick-up at enrollment, and 1201 (86%) were virologically suppressed at one year. Because of missing data on virologic suppression, primary results are based on a model incorporating multiple imputation. In addition to age and gender, distance from clinic and year of HIV diagnosis were included in the multivariable model. There was no difference in opting for clinic- vs. community-based pick-up with regard to achieving 12-month virologic suppression (aRR 1.02, 95% CI 0.98-1.05) in clinics offering choice. There was no impact of assigning all participants to an external pick-up point (aRR 1.00, 95% CI 0.95-1.06), but virologic suppression was reduced in the clinic that assigned participants to clinic pick-up (aRR 0.87, 95% CI 0.81-0.92). These results suggest that provision of community-based ART has not reduced continued virologic suppression in the population enrolled in the CCMDD program.

Geographic variation in 5-year mortality following HIV diagnosis: implications for clinical interventions.

Characterizing spatial distribution of HIV outcomes is vital for targeting interventions to areas most at risk. We performed spatial analysis to identify geographic clusters and factors associated with mortality in KwaZulu-Natal, South Africa. We utilized Sizanani trial (NCT01188941) data, which enrolled participants August 2010-January 2013 and obtained vital status at 5.8 (IQR 5.0-6.4) years of follow-up. We mapped geocoded addresses to 2011 Census-defined small area layer (SAL) centroids, used Kulldorff's spatial scan statistic to identify mortality clusters, and compared socio-demographic factors for SALs within and outside mortality clusters. We assigned 1,143 participants living with HIV (260 [23%] of whom died during follow-up) to 677 SALs. One lower mortality cluster (n = 90, RR = 0.23, p = 0.022) was identified near a hospital outside Durban. SALs in the cluster were younger (24y vs 25y, p < 0.001); had fewer bedrooms/household (3 vs 4, p < 0.001); had more females (52% vs 51%, p = 0.013) and residents with no schooling past age 20 (4% vs 3%, p < 0.001) or no education at all (4% vs 3%, p < 0.001); had fewer residents with income >3,200 ZAR/month (5% vs 9%, p < 0.001); and had reduced access to piped water (p < 0.001), refuse disposal (p < 0.001), and toilets (p < 0.001). Targeted interventions may improve outcomes in areas with similar characteristics.

Experiences of participants in a decentralized antiretroviral therapy program in South Africa during the COVID-19 pandemic.

The COVID-19 pandemic and associated restrictions could adversely affect long-term HIV care. We evaluated the experiences of people receiving antiretroviral therapy (ART) through a decentralized delivery program in South Africa during the COVID-19 pandemic. We telephoned a random subsample of participants enrolled in a prospective cohort study in KwaZulu-Natal in April and May 2020 and administered a semi-structured telephone interview to consenting participants. We completed interviews with 303 of 638 contacted participants (47%); 66% were female, with median age 36y. The most common concerns regarding the COVID-19 pandemic were food running out (121, 40%), fear of becoming infected with COVID-19 (103, 34%), and being unable to work/losing employment or income (102, 34%). Twenty-five (8%) participants had delayed ART pick-up due to the pandemic, while 212 (70%) had new concerns about ART access going forward. Mental health scores were worse during the pandemic compared to baseline (median score 65.0 vs 80.0, p < 0.001). Decentralized ART distribution systems have the potential to support patients outside of health facilities during the COVID-19 pandemic, but economic concerns and mental health impacts related to the pandemic must also be recognized and addressed.

Willingness to accept COVID-19 vaccination among people living with HIV in a high HIV prevalence community.

BACKGROUND: People living with HIV (PLWH) may have a poorer prognosis with COVID-19 infection and are an important population for COVID-19 vaccination. We assessed the willingness and reasons for COVID-19 vaccine acceptance or hesitancy among PLWH in South Africa. METHODS: We conducted a cross-sectional study consisting of telephone interviews with a randomly selected subset of participants enrolled in a prospective observational cohort study evaluating a decentralized antiretroviral therapy (ART) delivery program in South Africa. Questions assessed willingness to accept a future COVID-19 vaccine, concerns regarding COVID-19 vaccination, and overall vaccine confidence. Interviews were conducted between September 2020 and January 2021. We evaluated participant demographics, sources of COVID-19 information, stigma and medical mistrust, uptake of non-pharmaceutical interventions, and socioeconomic impacts of the COVID-19 pandemic as potential covariates of willingness to accept vaccination. RESULTS: We completed interviews with 213 participants; 153 (72%) were female, median age 35y, and 100 (47%) had completed secondary school. Among the participants, 121 (57%) were willing to accept future vaccination, 46 (22%) were unsure, and 45 (21%) stated they did not intend to be vaccinated. Fear of side effects, reported by 42 (20%), was the most common concern about COVID-19 vaccination. Older age was associated with willingness to accept vaccination (aOR 1.75 for every 10-year increase in age, 95% CI 1.10-2.78, p = 0.02), while higher medical mistrust related to COVID-19 (aOR 0.21, 95% CI 0.093-0.45, p < 0.001) and use of social media for COVID-19 information (aOR 0.30, 95% CI 0.11-0.84, p = 0.02) were associated with lower willingness to accept vaccination. CONCLUSIONS: In this cohort of PLWH in South Africa, over half were willing to accept COVID-19 vaccination, although a substantial proportion remained unsure or were not willing to be vaccinated. Public health messaging should emphasize the safety and efficacy of COVID-19 vaccination and address misinformation and medical mistrust among PLWH. Ongoing efforts to ensure access to COVID-19 vaccines for vulnerable populations are crucial.

Medical Mistrust and Stigma Associated with COVID-19 Among People Living with HIV in South Africa.

We evaluated COVID-19 stigma and medical mistrust among people living with HIV in South Africa. We conducted telephone interviews with participants in a prospective study of a decentralized antiretroviral therapy program. Scales assessing medical mistrust, conspiracy beliefs, anticipated and internalized stigma, and stereotypes specific to COVID-19 were adapted primarily from the HIV literature, with higher scores indicating more stigma or mistrust. Among 303 participants, the median stigma summary score was 4 [interquartile range (IQR) 0-8; possible range 0-24] and 6 (IQR 2-9) for mistrust (possible range 0-28). A substantial proportion of participants agreed or strongly agreed with at least one item assessing stigma (54%) or mistrust (43%). Higher COVID-19 stigma was associated with female gender and antecedent HIV stigma, and lower stigma with reporting television as a source of information on COVID-19. Further efforts should focus on effects of stigma and mistrust on protective health behaviors and vaccine hesitancy.

Public Opinions and Attitudes toward Noninvasive Prenatal Testing on Reddit: Content and Sentiment Analysis.

INTRODUCTION: Noninvasive prenatal testing (NIPT) can be used to detect fetal chromosomal abnormalities early in pregnancy. As eligibility criteria broaden and screening targets expand, gauging public acceptability of NIPT becomes increasingly important. Leveraging social media as a rich source of public discourse, the purpose of this study was to understand public opinions and attitudes toward NIPT on the social media platform Reddit. METHODS: We applied content and natural language processing techniques (i.e., sentiment analysis) to textual data collected from 4 Reddit communities focusing on the NIPT content posted from September 2012 to September 2022 (367 posts and 7,822 comments in total). RESULTS: Content analysis findings indicated that social media users consider NIPT to be worthwhile. Reasons NIPT was perceived to be not worthwhile related to unwanted anxiety, and the fact that NIPT results would not change anything about their approach to pregnancy were also expressed. The sentiment analysis identified more positive than negative emotions; the mean sentiment scores ranged from 0.48 to 1.22, depending on the specific Lexicon used. Specific emotions (i.e., trust, fear) were also identified. CONCLUSION: Our novel approach to understanding public perception and attitudes toward NIPT yielded results that are consistent with conventional patient-oriented research methods. These findings may not only contribute to ongoing improvements in prenatal patient care, research, and policy but also indicate that sentiment analysis applied to social media data can serve as a suitable means to assess public acceptability of NIPT, particularly as public dialogue on this topic increases over time.

Combining sarcopenia and ASA status to inform emergency laparotomy outcomes: could it be that simple?

BACKGROUND: Risk assessment for emergency laparotomy (EL) is important for guiding decision-making and anticipating the level of perioperative care in acute clinical settings. While established tools such as the American College of Surgeons National Surgical Quality Improvement Program calculator (ACS-NSQIP), the National Emergency Laparotomy Audit Risk Prediction Calculator (NELA) and the Portsmouth Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity calculation (P-POSSUM) are accurate predictors for mortality, there has been increasing recognition of the benefits from including measurements for frailty in a simple and quantifiable manner. Psoas muscle to 3rd lumbar vertebra area ratio (PM:L3) measured on CT scans was proven to have a significant inverse association with 30-, 90- and 365-day mortality in EL patients. METHODS: A retrospective analysis was conducted of 500 patients admitted to four Australian hospitals who underwent EL during 2016-2017, and had contemporaneous abdomino-pelvic CT scans. Radiological sarcopenia was measured as PM:L3 ratios. ASC-NSQIP, NELA and P-POSSUM were retrospectively calculated. Univariate and multivariate logistic regression modelling was used to assess these ratios and scores, as well as American Society of Anaesthesiologists (ASA) classification separated into ASA I-III and IV/V (simplified ASA), as potential predictors of 30-, 90- and 365-day mortality. RESULTS: PM:L3, simplified ASA, ACS-NSQIP, NELA and P-POSSUM were each statistically significant predictors of 30-day, 90-day and 365-day mortality (P < 0.001). Logistic regression models of 30-, 90- and 365-day mortality combining PM:L3 (P = 0.001) and simplified ASA (P < 0.001) exhibited AUCs of 0.838 (0.780, 0.896), 0.805 (0.751, 0.860) and 0.775 (0.729, 0.822), respectively, which were comparable to that of ACS-NSQIP and NELA. CONCLUSION: Combining the semi-physiological parameter ASA classification with PM:L3 provides a quick and simple alternative to the more complex established risk assessment scores and is superior to PM:L3 alone.

Getting back 'home' after emergency laparotomy: how many never make it?

BACKGROUND: Emergency laparotomy (EL) is performed on about 15 500 patients in Australia each year. Aside from mortality there is significant concern about the possibility that previously independent patients discharged after EL will become reliant on long-term dependent care. This study aimed to establish the proportion of patients not returning to their pre-admission residence, a proxy for dependent care, following EL. METHODS: Data were collected on all adult patients who underwent EL across four Australian hospitals over 2 years. A total of 113 data points were collected including pre-hospital residence, discharge destination, mortality and place of residence at 90 and 365 days. RESULTS: A total of 782 patients underwent EL, the mean age was 64 years. Pre-admission, 95.5% of patients were living in their own home. Inpatient mortality was 7.0% and at discharge 72.4% of patients returned directly back to their pre-hospital residence. At 90 days, mortality was 10.5%, and 87% of patients had returned to their pre-hospital residence, including all patients under 70 years of age. By 365 days, overall mortality was 16.8%, and only 1.5% of patients (all aged >70 years) had not returned to their pre-hospital residence. CONCLUSION: Patients who survive 90 and 365 days following EL nearly all return to their pre-hospital residence, with only a very small proportion of previously independent patients entering dependent care. This should help inform shared decision-making regarding emergency laparotomy in the acute setting.

Sarcopenia 'made simple' and outcomes from emergency laparotomy.

BACKGROUND: Emergency Laparotomy (EL) is recognized as high-risk surgery with high mortality. Established surgical risk assessment tools (NELA Risk Prediction Calculator, P-POSSUM, ACS-NSQIP) are accurate predictors of morbidity and mortality. However, their multicomponent complexity limits their use in practice. Sarcopenia is associated with poorer surgical outcomes. This study tests for an association between a simple measure of radiological sarcopenia and mortality in EL patients in an Australian cohort. METHODS: A retrospective analysis was conducted of 500 patients admitted to four Australian hospitals who underwent EL during 2016-2017. All patients had a contemporaneous abdomino-pelvic CT scan. Radiological sarcopenia was measured as the ratio of total psoas muscle area (PM) to L3 vertebral body cross sectional area (PM:L3). Patients were followed up to 12 months. Primary outcomes were 30-, 90- and 365-day mortality. RESULTS: The mean 30-day mortality predictions for NELA, P-POSSUM and ACS-NSQIP were 11.36%, 17.28% and 11.30% respectively. PM:L3 ratio was associated with 30-, 90- and 365-day mortality (P < 0.001) and sex (P < 0.001) and negatively correlated with age (r = -0.4612; P < 0.001). Radiological sarcopenia had a weak negative correlation with NELA (r = -0.2737; P < 0.001), P-POSSUM (r = -0.1880; P < 0.001) and ACS-NSQIP (r = -0.2351; P < 0.001). The latter three metrics were significantly correlated (r > 0.5696; P < 0.001). CONCLUSION: Radiological sarcopenia (CT-assessed PM:L3) is a significant predictor of mortality in EL patients in Australia. The results of this study suggest that radiological sarcopenia is equivalent to established risk assessment tools. The more timely and easily accessible CT-assessed PM:L3 metric is potentially automatable and may have significant utility in clinical practice.

Willingness to accept COVID-19 vaccination among people living with HIV in a high HIV prevalence community.

Background People living with HIV (PLWH) may have a poorer prognosis with COVID-19 infection and are an important population for COVID-19 vaccination. We assessed the willingness and reasons for COVID-19 vaccine acceptance or hesitancy among PLWH in South Africa. Methods We conducted a cross-sectional study consisting of telephone interviews with a randomly selected subset of participants enrolled in a prospective observational cohort study evaluating a decentralized antiretroviral therapy (ART) delivery program in South Africa. Questions assessed willingness to accept a future COVID-19 vaccine, concerns regarding COVID-19 vaccination, and overall vaccine confidence. Interviews were conducted between September 2020 and January 2021. We evaluated participant demographics, sources of COVID-19 information, stigma and medical mistrust, uptake of non-pharmaceutical interventions, and socioeconomic impacts of the COVID-19 pandemic as potential covariates of willingness to accept vaccination. Results We completed interviews with 213 participants; 153 (72%) were female, median age 35y, and 100 (47%) had completed secondary school. Among the participants, 121 (57%) were willing to accept future vaccination, 46 (22%) were unsure, and 45 (21%) stated they did not intend to be vaccinated. Fear of side effects, reported by 42 (20%), was the most common concern about COVID-19 vaccination. Older age was associated with willingness to accept vaccination (aOR 1.75 for every 10-year increase in age, 95% CI 1.10-2.78, p=0.02), while higher medical mistrust related to COVID-19 (aOR 0.21, 95% CI 0.093-0.45, p<0.001) and use of social media for COVID-19 information (aOR 0.30, 95% CI 0.11-0.84, p=0.02) were associated with lower willingness to accept vaccination. Conclusions In this cohort of PLWH in South Africa, over half were willing to accept COVID-19 vaccination, although a substantial proportion remained unsure or were not willing to be vaccinated. Public health messaging should emphasize the safety and efficacy of COVID-19 vaccination and address misinformation and medical mistrust among PLWH. Ongoing efforts to ensure access to COVID-19 vaccines for vulnerable populations are crucial.

Saturation variant interpretation using CRISPR prime editing.

High-throughput functional characterization of genetic variants in their endogenous locus has so far been possible only with methods that rely on homology-directed repair, which are limited by low editing efficiencies. Here, we adapted CRISPR prime editing for high-throughput variant classification and combined it with a strategy that allows for haploidization of any locus, which simplifies variant interpretation. We demonstrate the utility of saturation prime editing (SPE) by applying it to the NPC intracellular cholesterol transporter 1 gene (NPC1), mutations in which cause the lysosomal storage disorder Niemann-Pick disease type C. Our data suggest that NPC1 is very sensitive to genetic perturbation, with 410 of 706 assayed missense mutations being classified as deleterious, and that the derived function score of variants is reflective of diverse molecular defects. We further applied our approach to the BRCA2 gene, demonstrating that SPE is translatable to other genes with an appropriate cellular assay. In sum, we show that SPE allows for efficient, accurate functional characterization of genetic variants.

Uptake of community- versus clinic-based antiretroviral therapy dispensing in the Central Chronic Medication Dispensing and Distribution program in South Africa.

INTRODUCTION: South Africa's government-led Central Chronic Medication Dispensing and Distribution (CCMDD) program offers people living with HIV the option to collect antiretroviral therapy at their choice of community- or clinic-based pick-up points intended to increase convenience and decongest clinics. To understand CCMDD pick-up point use among people living with HIV, we evaluated factors associated with uptake of a community- versus clinic-based pick-up point at CCMDD enrolment. METHODS: We collected baseline data from October 2018 to March 2020 on adults (≥18 years) who met CCMDD clinical eligibility criteria (non-pregnant, on antiretroviral therapy for ≥1 year and virologically suppressed) as part of an observational cohort in seven public clinics in KwaZulu-Natal. We identified factors associated with community-based pick-up point uptake and fit a multivariable logistic regression model, including age, gender, employment status, self-perceived barriers to care, self-efficacy, HIV-related discrimination, and perceived benefits and challenges of CCMDD. RESULTS AND DISCUSSION: Among 1521 participants, 67% were females, with median age 36 years (IQR 30-44). Uptake of a community-based pick-up point was associated with younger age (aOR 1.18 per 10-year decrease, 95% CI 1.05-1.33), being employed ≥40 hours per week (aOR 1.42, 95% CI 1.10-1.83) versus being unemployed, no self-perceived barriers to care (aOR 1.42, 95% CI 1.09-1.86) and scoring between 36 and 39 (aOR 1.44, 95% CI 1.03-2.01) or 40 (aOR 1.91, 95% CI 1.39-2.63) versus 10-35 on the self-efficacy scale, where higher scores indicate greater self-efficacy. Additional factors included more convenient pick-up point location (aOR 2.32, 95% CI 1.77-3.04) or hours (aOR 5.09, 95% CI 3.71-6.98) as perceived benefits of CCMDD, and lack of in-clinic follow-up after a missed collection date as a perceived challenge of CCMDD (aOR 4.37, 95% CI 2.30-8.31). CONCLUSIONS: Uptake of community-based pick-up was associated with younger age, full-time employment, and systemic and structural factors of living with HIV (no self-perceived barriers to care and high self-efficacy), as well as perceptions of CCMDD (convenient pick-up point location and hours, lack of in-clinic follow-up). Strategies to facilitate community-based pick-up point uptake should be tailored to patients' age, employment, self-perceived barriers to care and self-efficacy to maximize the impact of CCMDD in decongesting clinics.

Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response.

BACKGROUND: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. OBJECTIVE: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. METHODS: This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. RESULTS: In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P < 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P < 0.001). Evidence of mediation was more pronounced in patients < 65 years (proportion mediated = 0.52 [P < 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626). CONCLUSION: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients < 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.

High prevalence of extended-spectrum beta-lactamase organisms and the COVID-19 pandemic impact on donor recruitment for fecal microbiota transplantation in Hong Kong.

BACKGROUND: With increasing number of clinical trials relating to fecal microbiota transplantation (FMT), it is crucial to identify and recruit long-term, healthy, and regular fecal donors. OBJECTIVE: We aimed to report the outcomes of screening and recruitment of fecal donors for FMT. METHODS: Potential donors were recruited via advertisement through internal mass emails at a university. They were required to undergo a pre-screening telephone interview, a detailed questionnaire, followed by blood and stool investigations. RESULTS: From January 2017 to December 2020, 119 potential donors were assessed with 75 failed pre-screening. Reasons for failure included: inability to come back for regular and long-term donation (n = 19), high body mass index (n = 17), underlying chronic illness or on long-term medications (n = 11), being healthcare professionals (n = 10), use of antibiotics within 3 months (n = 5) and others (n = 13). Forty-four donors completed questionnaires and 11 did not fulfill the clinical criteria. Of the remaining 33 potential donors who had stool and blood tests, 21 failed stool investigations (19 extended-spectrum beta-lactamase [ESBL] organisms, one Clostridioides difficile, one C. difficile plus Methicillin Resistant Staphylococcus aureus), one failed blood tests (high serum alkaline phosphatase level), one required long-term medication and nine withdrew consent and/or lost to follow-up. In total, only one out of 119 (0.8%) potential donors was successfully recruited as a regular donor. CONCLUSION: There was a high failure rate in donor screening for FMT. Main reasons for screening failure included high prevalence of positive ESBL organisms in stool and failed commitment to regular stool donation.

Non-invasive prenatal screening of fetal sex chromosomal abnormalities: perspective of pregnant women.

OBJECTIVE: To study whether pregnant women would like to be informed if sex chromosomal abnormalities (SCA) were suspected with the non-invasive prenatal diagnosis of fetal Down syndrome (the NIFTY) test. METHODS: Two hundred and one patients carried a singleton pregnancy requesting the NIFTY test were invited to give their preferences if there was suspicion of SCA by the NIFTY test. RESULTS: Over 93.5% were ethnic Chinese, with a mean age of 36. Prior Down screening was positive in 66 (32.8%). Over 50% of subjects considered SCA to be better in terms of disability compared to Down syndrome, and only 5.2% considered SCA to be worse. Yet, the majority (198, 98.5%) indicated that they wanted to be informed if there was suspicion of SCA. Of whom 34.8% would have an amniocentesis for confirmation, while 57.1% were not certain, indicating the possibility of accepting these conditions. CONCLUSION: Besides screening Down syndrome by NIFTY, most pregnant women would also like to be informed if there was suspicion of SCA. Those screened positive should be counseled by those with experience in genetics to avoid unnecessary pregnancy termination.

Clinical utility of noninvasive fetal trisomy (NIFTY) test--early experience.

OBJECTIVE: To report the initial experience of noninvasive prenatal diagnosis of fetal Down syndrome (The NIFTY test) in a clinical setting. METHODS: The NIFTY test was offered as a screening test for fetal Down syndrome to pregnant women with a singleton pregnancy at 12 weeks of gestation or beyond. A satisfaction questionnaire was sent to the first 400 patients. RESULTS: During a 6-month period, 567 NIFTY tests were performed. Over 90% of those studied were ethnic Chinese, and the mean age of the women studied was 36 years. The test was performed at 12-13 weeks of gestation in 49.21%. The median reporting time was 9 days. The test was positive for trisomy 21 in eight cases, and for trisomy 18 in 1 case; all were confirmed by fetal karyotyping. There was no false-positive result. Of the questionnaires, 182 completed responses were received. Over 95% had complete or almost complete resolution of anxiety. Except for one, all were satisfied with the NIFTY test, and all indicated that they would recommend the test to their friends. CONCLUSION: The NIFTY test was a highly specific test. Unnecessary invasive tests and associated fetal losses could be avoided in almost all women who have a normal fetus.

Factors associated with successful Chopart amputation in patients with diabetes: a systematic review.

Chopart amputations were first performed for treatment of a non-salvageable distal foot but became unfavorable because of the development of equinovarus contractures and ulcerations. The majority of below-knee amputations today occur in ambulatory patients with diabetes in which a Chopart amputation may be a viable option; however, the durability of the residual limb is questionable. The authors undertook a systematic review of electronic databases and other relevant sources to identify material relating to the factors associated with a successful Chopart amputation in ambulatory patients with diabetes. Studies were eligible for inclusion only if they consecutively enrolled ambulatory patients with diabetes who underwent a Chopart amputation, regardless of etiology, with or without any tendinous or osseous balancing performed and had a mean follow-up of ≥12 months duration. Four studies involving 74 patients/feet were identified that met the inclusion criteria with a weighted mean follow-up of 21.1 months. The efficacy of tendinous and/or osseous balancing could not be assessed because of the lack of comparable techniques. However, review of the included studies supports that a residual functional limb can be maintained for ≥12 months with the use of a properly fitting high-profile prosthetic device for lifelong ambulation.