Diagnosis and treatment of infected wounds: A multi-centre audit of current clinical practice across the UK, Ireland and Scandinavia.

AIMS AND OBJECTIVES: Surveillance of wound infection including signs of infection alongside antimicrobial usage (types, duration, frequency) can highlight knowledge gaps and inconsistencies. This manuscript aims to highlight these, identify and inform opportunities for practice improvement and to show impact of infection management practice may be having on the issue of antimicrobial resistance. BACKGROUND: Infected wounds pose challenges to healthcare professionals. Balancing risk of wound deterioration and progression to systemic infection with appropriate use of antimicrobials is necessary to minimise development of resistance. METHODS: Analysis consisted of a practice survey of 9661 wounds across 70 community sites over a period of one week. Data were collected from projects between 2017 and 2020. The form was available to providers within the UK, Ireland, Norway, Denmark, Sweden and Finland. EQUATOR research guidelines were followed; STROBE checklist for observational research reporting was completed. RESULTS: Infection rates of 8.9% were reported from wounds assessed. These data indicate inconsistencies with diagnosis across practice with non-specialists more likely to be unsure of wound infection. Greater confidence in infection identification was observed as number of signs increased. Inconsistencies were also observed in appropriate treatment; antimicrobials were used in 35% of wounds considered not infected and not used in 41% of wounds that were identified as infected. CONCLUSIONS: This investigation of infection management practice of over 9000 wounds provides an insight into diagnosis and treatment of infection. Inconsistencies in diagnosis and treatment of wound infections reported highlight the need for increased education, awareness of diagnosis and treatment of infection. RELEVANCE TO CLINICAL PRACTICE: Variability in management of infected wounds highlights opportunities to aid more effective diagnosis and treatment of infected wounds. Incorporation of support tools or evidence-based pathways into practice may enhance confidence in management of local infection, balanced with appropriate use, potentially minimising resistance and improving outcomes.

Acute chest syndrome in pediatric sickle cell disease: Associations with racial composition and neighborhood deprivation.

BACKGROUND: Acute chest syndrome (ACS) is the leading cause of death for children with sickle cell disease (SCD). Recurrent ACS has detrimental effects on pulmonary health and health care costs. Neighborhood characteristics affect the outcomes of many pediatric chronic diseases, but their role in SCD is not well studied. In this study, we investigated the effects of area-level socioeconomic deprivation and racial composition on the recurrence of ACS. STUDY DESIGN: We performed a retrospective cross-sectional analysis of clinical data from a large pediatric SCD center. Patients' residential addresses were geocoded and linked to a composite area deprivation index (ADI) and percent African American population at the level of Census block groups. The association of recurrent ACS with neighborhood characteristics was evaluated using logistic regression analysis. RESULTS: The sample included 709 children with SCD. Residence in a socioeconomically deprived neighborhood was associated with 27% less risk of recurrent ACS, and residence in a predominantly African American neighborhood was associated with 41% less risk of ACS recurrence. The racial composition explained the protective effect of living in a high-deprivation area after adjusting for sociodemographic and clinical covariates. Demographic and clinical factors associated with recurrent ACS included older age, male gender, asthma, hydroxyurea use, and chronic transfusion therapy. CONCLUSIONS: This is the first study to report a protective effect of residing in a predominantly African American community for ACS recurrence. Further prospective studies are needed to confirm the association and to understand the mechanisms of such relationship.

Evaluation of a health system intervention to improve virological management in an antiretroviral programme at a municipal clinic in central Durban.

BACKGROUND: With the largest antiretroviral therapy (ART) programme globally, demand for effective HIV management is increasing in South Africa. While viral load (VL) testing is conducted, VL follow-up and management are sub-optimal. OBJECTIVES: The objective of this study was to address gaps in the VL cascade to improve VL testing and management. METHODS: Antiretroviral therapy records were sampled for an in-depth review. The study team then reviewed individual records, focusing on ART management, virological suppression and retention. Multifaceted interventions focused on virological control, including a clinical summary chart for ART care; streamlining laboratory results receipt and management; monitoring VL suppression, flagging virological failure and missed visits for follow-up; down-referral of stable patients eligible for the chronic club system; and training of personnel and patients. RESULTS: Pre-intervention, 78% (94/120) of eligible patients had VL tests, versus 92% (145/158) post-intervention (p = 0.0009). Pre-intervention, 59% (71/120) of patients accessed their VL results, versus 86% (136/158) post-intervention (p < 0.0001). Post-intervention, 73% (19/26) of patients eligible for ART change were appropriately managed, versus 11% (4/36) pre-intervention (p < 0.0001). Only 27% had no regimen changes (7/26) post-intervention, versus 81% (29/36) pre-intervention (p < 0.0001). CONCLUSION: Service delivery was streamlined to facilitate HIV services by focusing on VL test monitoring, protocol training and accessibility of results, thereby improving clinical management.

Providing cost-effective treatment of hard-to-heal wounds in the community through use of NPWT.

OBJECTIVE: The treatment of non-healing wounds accounts for a high proportion of wound care costs. Advanced technology treatments, such as negative pressure wound therapy (NPWT), could be cost-effective if they result in faster healing. The objective of this study is to assess the effect on healing and the cost-effectiveness of a single-use NPWT (i.e PICO by Smith & Nephew) when used on hard-to-heal wounds in a community setting. METHOD: This was a cohort case study in which wounds were treated with NWPT for 2 weeks. Wounds were assessed every 2-4 weeks to a healed state. The weekly cost of treatment prior to intervention, that is, the products used and nurse time, were compared with treatment costs associated with NWPT and after a return to standard treatment. RESULTS: The study included 9 patients with leg ulcers or pressure ulcers that had been slow healing or non-healing for at least 6 weeks. While treated with NPWT, the average weekly reduction in wound size was 21%. The wound size achieved with NPWT was reached on average 10 weeks earlier than predicted. The increased healing rate continued after PICO stopped and 5 wounds healed on average 8 weeks later. Frequency of dressing changes fell from 4 times weekly at baseline to 2 times a week with NPWT and to 1.8 after NPWT stopped. Weekly cost of treatment with NPWT was, on average, 1.6 times higher than the baseline, but fell to 3 times less when NPWT stopped owing to the reduction in dressing changes. The amount of change in healing rate was considerably higher than the increase in costs associated with NPWT. CONCLUSION: NWPT is a cost-effective treatment for hard-to-heal wounds. Wounds decreased in size and healed more quickly under NWPT treatment than under standard treatment. Additional NPWT costs can be quickly offset by faster healing and a shortened treatment period.

Concurrent use of traditional medicine and ART: Perspectives of patients, providers and traditional healers in Durban, South Africa.

The concurrent use of traditional African medicine (TAM) and allopathic medicine is not well understood for people living with HIV (PLHIV) in the era of antiretroviral therapy (ART). This cross-sectional, qualitative study examines perceptions of the concurrent use of TAM and ART among: (1) patients receiving ART at the Sinikithemba HIV Clinic of McCord Hospital, in Durban, South Africa; (2) allopathic medical providers (doctors, nurses and HIV counsellors) from Sinikithemba; and (3) local traditional healers. Data were collected through in-depth interviews and focus group discussions with 26 participants between July and October, 2011. Patients in this study did not view TAM as an alternative to ART; rather, results show that patients employ TAM and ART for distinctly different needs. More research is needed to further understand the relationship between traditional and allopathic approaches to health care in South Africa, to improve cultural relevance in the provision and delivery of care for PLHIV, and to pragmatically address the concerns of health care providers and public health officials managing this intersection in South Africa and elsewhere.

Gender-specific risk factors for virologic failure in KwaZulu-Natal: automobile ownership and financial insecurity.

We sought to examine which socioeconomic indicators are risk factors for virologic failure among HIV-1 infected patients receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa. A case-control study of virologic failure was conducted among patients recruited from the outpatient clinic at McCord Hospital in Durban, South Africa between October 1, 2010 and June 30, 2012. Cases were those failing first-line ART, defined as viral load >1,000 copies/mL. Univariate logistic regression was performed on sociodemographic data for the outcome of virologic failure. Variables found significant (p < 0.05) were used in multivariate models and all models were stratified by gender. Of 158 cases and 300 controls, 35 % were male and median age was 40 years. Gender stratification of models revealed automobile ownership was a risk factor among males, while variables of financial insecurity (unemployment, non-spouse family paying for care, staying with family) were risk factors for women. In this cohort, financial insecurity among women and automobile ownership among men were risk factors for virologic failure. Risk factor differences between genders demonstrate limitations of generalized risk factor analysis.

Early warning indicators for first-line virologic failure independent of adherence measures in a South African urban clinic.

We sought to develop individual-level Early Warning Indicators (EWI) of virologic failure (VF) for clinicians to use during routine care complementing WHO population-level EWI. A case-control study was conducted at a Durban clinic. Patients after ≥ 5 months of first-line antiretroviral therapy (ART) were defined as cases if they had VF [HIV-1 viral load (VL)>1000 copies/mL] and controls (2:1) if they had VL ≤ 1000 copies/mL. Pharmacy refills and pill counts were used as adherence measures. Participants responded to a questionnaire including validated psychosocial and symptom scales. Data were also collected from the medical record. Multivariable logistic regression models of VF included factors associated with VF (p<0.05) in univariable analyses. We enrolled 158 cases and 300 controls. In the final multivariable model, male gender, not having an active religious faith, practicing unsafe sex, having a family member with HIV, not being pleased with the clinic experience, symptoms of depression, fatigue, or rash, low CD4 counts, family recommending HIV care, and using a TV/radio as ART reminders (compared to mobile phones) were associated with VF independent of adherence measures. In this setting, we identified several key individual-level EWI associated with VF including novel psychosocial factors independent of adherence measures.

High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen.

OBJECTIVE: We sought to determine the rate of the K65R mutation in patients receiving tenofovir (TDF)-based antiretroviral therapy (ART) with subtype C HIV infection. DESIGN: Retrospective cohort study. METHODS: All patients initiated on stavudine (d4T) with lamivudine (3TC) or TDF with 3TC and a nonnucleoside reverse transcriptase inhibitor at McCord Hospital in Durban, South Africa had their charts reviewed. All patients with virologic failure, defined as a viral load more than 1000 copies/ml after 5 months of a first ART regimen, had genotypic resistance testing performed prospectively using a validated in-house assay. Important resistance mutations were selected based upon published mutations in subtype B virus in the Stanford HIV Drug Resistance database. RESULTS: A total of 585 patients were initiated on TDF-containing first-line ART from 3 August 2010 to 17 March 2011. Thirty-five (6.0%) of these patients had virologic failure and 23 of 33 (69.7%) of the virologic failure patients had the K65R mutation. The median (interquartile range) for the baseline CD4 cell count was 105 cells/µl (49-209) and viral load at virologic failure was 47 571 copies/ml (20 708-202 000). During the same period, 53 patients were initiated on d4T-containing regimens. Two (3.8%) of these patients had virologic failure and one of the virologic failure patients had the K65R mutation. CONCLUSION: Preliminary data show very high rates (>65%) of K65R for patients failing TDF-based first-line regimens at McCord Hospital with few additional nucleoside reverse transcriptase inhibitor mutations compared with subtype B. These rates may reflect faster in-vivo selection, longer time on a failing regimen or transmitted drug resistance.

A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy.

BACKGROUND: Stavudine continues to be used in antiretroviral treatment (ART) regimens in many resource-limited settings. The use of zidovudine instead of stavudine in higher-risk patients to reduce the likelihood of lactic acidosis and hyperlactatemia (LAHL) has not been examined. METHODS: Antiretroviral-naïve, HIV-infected adults initiating ART between 2004 and 2007 were divided into cohorts of those initiated on stavudine- or zidovudine-containing therapy. We evaluated stavudine or zidovudine use, age, sex, body mass index (BMI), baseline CD4 cell count, creatinine, hemoglobin, alanine aminotransferase, and albumin as predictors of time to LAHL with Cox Proportional Hazards (PH) regression models. RESULTS: Among 2062 patients contributing 2747 patient years (PY), the combined incidence of LAHL was 3.2/100 PY in those initiating stavudine- and 0.34/100 PY in those initiating zidovudine-containing ART (RR 9.26, 95% CI: 1.28-66.93). In multivariable Cox PH analysis, stavudine exposure (HR 14.31, 95% CI: 5.79-35.30), female sex (HR 3.41, 95% CI: 1.89-6.19), higher BMI (HR 3.21, 95% CI: 2.16-4.77), higher creatinine (1.63, 95% CI: 1.12-2.36), higher albumin (HR 1.04, 95% CI: 1.01-1.07), and lower CD4 cell count (HR 0.96, 95% CI: 0.92-1.0) at baseline were associated with higher LAHL rates. Among participants who started on stavudine, switching to zidovudine was associated with lower LAHL rates (HR 0.15, 95% CI: 0.06-0.35). Subgroup analysis limited to women with higher BMI≥25 kg/m2 initiated on stavudine also showed that switch to zidovudine was protective when controlling for other risk factors (HR 0.21, 95% CI .07-0.64). CONCLUSIONS: Stavudine exposure, female sex, and higher BMI are strong, independent predictors for developing LAHL. Patients with risk factors for lactic acidosis have less LAHL while on zidovudine- rather than stavudine-containing ART. Switching patients from stavudine to zidovudine is protective. Countries continuing to use stavudine should avoid this drug in women and patients with higher BMI.

Prevalence of HIV-1 drug resistance after failure of a first highly active antiretroviral therapy regimen in KwaZulu Natal, South Africa.

BACKGROUND: Emergence of human immunodeficiency virus type 1 (HIV-1) drug resistance may limit the benefits of antiretroviral therapy in resource-limited settings. The prevalence of resistance was assessed among patients from KwaZulu Natal, South Africa, following failure of their first highly active antiretroviral therapy (HAART) regimen. METHODS: Genotypic resistance testing was performed on plasma virus samples from patients who experienced virologic failure of their first HAART regimen at 2 clinics in KwaZulu Natal. Clinical and demographic data were obtained from medical records. Regression analysis was performed to determine factors associated with > or =1 significant drug resistance mutation. RESULTS: From January 2005 through August 2006, a total of 124 antiretroviral-treated adults who experienced virologic failure were enrolled. The predominant subtype was HIV-1C. Virus samples from 83.5% of participants carried > or =1 significant drug resistance mutation. Dual-class drug-resistant virus was present in 64.3% of participants, and 2.6% had virus with triple-class drug resistance. The most common mutation was M184V/I (64.3% of patients); K103N was present in virus from 51.3%, and V106M was present in virus from 19.1%. Thymidine analog resistance mutations were found in virus from 32.2% of patients, and protease resistance mutations were found in virus from 4.4%. CONCLUSIONS: Antiretroviral drug-resistant virus was detected in >80% of South African patients who experienced failure of a first HAART regimen. Patterns of drug resistance reflected drugs used in first-line regimens and viral subtype. Continued surveillance of resistance patterns is warranted to guide selection of second-line regimens.