The Impacts of Residential Location on the Risk of HIV Virologic Failure Among ART Users in Durban, South Africa.

Using a case-control study of patients receiving antiretroviral treatment (ART) in 2010-2012 at McCord Hospital in Durban, South Africa, we sought to understand how residential locations impact patients' risk of virologic failure (VF). Using generalized estimating equations to fit logistic regression models, we estimated the associations of VF with socioeconomic status (SES) and geographic access to care. We then determined whether neighborhood-level poverty modifies the association between individual-level SES and VF. Automobile ownership for men and having non-spouse family members pay medical care for women remained independently associated with increased odds of VF for patients dwelling in moderately and severely poor neighborhoods. Closer geographic proximity to medical care was positively associated with VF among men, while higher neighborhood-level poverty was positively associated with VF among women. The programmatic implications of our findings include developing ART adherence interventions that address the role of gender in both the socioeconomic and geographical contexts.

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.

Factors that contribute to patient length of stay in the emergency department: A time in motion observational study.

OBJECTIVES: Increased Emergency Department length of stay impacts access to emergency care and is associated with increased patient morbidity, overcrowding, reduced patient and staff satisfaction. We sought to determine the contributing factors to increased length of stay in our mixed ED. METHODS: A real-time observational study was conducted at Wollongong Hospital over a continuous 72-h period. Times of intervention, assessment and treatment were recorded by dedicated emergency medical or nurse observers. The time from triage to each event was calculated and descriptive analyses performed. Free text comments were analysed using inductive content analysis. RESULTS: Data were collected on 381 of 389 eligible patients. The largest time delays were experienced by patients who required a CT, specialist review and/or an inpatient bed. Registrars and nurse practitioners were the most efficient in reaching a decision to admit or discharge. The time from triage to specialist review increased with the number requested (148 min for one, 224 min for two and 285 min for three). The longest length of stay was experienced by mental health and paediatric patients. CONCLUSIONS: The main delays contributing to ED length of stay were CT imaging and specialist reviews. Overcrowding in ED need targeted, site-specific interventions.

Rapid development and implementation of a behaviour change strategy to improve COVID-19 personal protective equipment use in a regional Australian emergency department.

OBJECTIVE: To identify barriers to, describe the development of and evaluate the implementation of a behavioural theory informed strategy to improve staff personal protective equipment (PPE) compliance during COVID-19 in a regional Australian Emergency Department. METHODS: Barriers to PPE use were identified through staff consultation then categorised using the Theoretical Domains Framework. The Behaviour Change Wheel was used to develop a strategy to address the barriers to PPE compliance. The strategy was refined and endorsed by the site COVID taskforce. Data were collected through direct observation. Descriptive statistics were used to summarise PPE compliance and inductive content analysis for free text data of staff behaviours. RESULTS: 73 barriers were identified, mapped to 9 intervention functions and 42 behaviour change techniques. The predominant mechanisms were: (1) Executive communication reinforcing policy and consequences; (2) implementation of a PPE Marshal; (3) face to face reinforcement / modeling; (4) environmental restructuring including electronic medical record modifications. The PPE Marshal observed 281 PPE activities. PPE compliance varied between 47.9% (Buddy check) and 91.8% (Bare below elbow). The PPE Marshal intervened on 121 occasions, predominantly through buddying, explaining and demonstrating correct PPE use, most frequently with medical staff (72%). CONCLUSION: We describe an evidence-based process to overcome barriers to PPE compliance that maximize safe work practice in a time critical situation. Staff require enabling, access to equipment and reinforcement to use PPE correctly.

Counselor- versus provider-based HIV screening in the emergency department: results from the universal screening for HIV infection in the emergency room (USHER) randomized controlled trial.

OBJECTIVE: We compare rates of rapid HIV testing, test offer, and acceptance in an urban emergency department (ED) when conducted by dedicated HIV counselors versus current members of the ED staff. METHODS: The Universal Screening for HIV Infection in the Emergency Room [USHER] trial is a prospective randomized controlled trial that implemented an HIV screening program in the ED of an urban tertiary medical center. ED patients were screened and consented for trial enrollment by an USHER research assistant. Eligible subjects were randomized to rapid HIV testing (oral OraQuick) offered by a dedicated counselor (counselor arm) or by an ED provider (provider arm). In the counselor arm, counselors-without other clinical responsibilities-assumed nearly all testing-related activities (consent, counseling, delivery of test results). In the provider arm, trained ED emergency service assistants (nursing assistants) consented and tested the participant in the context of other ED-related responsibilities. In this arm, ED house officers, physician assistants, or attending physicians provided HIV test results to trial participants. Outcome measures were rates of HIV testing and test offer among individuals consenting for study participation. Among individuals offered the test, test acceptance was also measured. RESULTS: From February 2007 through July 2008, 8,187 eligible patients were approached in the ED, and 4,855 (59%) consented and were randomized to trial participation. The mean age was 37 years, 65% were women, and 42% were white. The overall testing rate favored the counselor arm (57% versus 27%; P<.001); 80% (1,959/2,446) of subjects in the counselor arm were offered an HIV test compared with 36% (861/2,409) in the provider arm (P<.001). HIV test acceptance was slightly higher in the provider arm (counselor arm 71% versus provider arm 75%; P = .025). CONCLUSION: Routine rapid HIV testing in the ED was accomplished more frequently by dedicated HIV counselors than by ED staff in the course of routine clinical work. Without dedicated staff, HIV testing in this setting may not be truly routine.

Nail Tumors.

This article describes nail tumors and their clinical features, biologic behavior, and treatment. Tumors included are onychopapilloma, onychomatricoma, periungual fibromas/fibrokeratomas, glomus tumors, subungual exostosis, myxoid cysts, and squamous cell carcinoma.

Analysis of genetic copy number changes in cervical disease progression.

BACKGROUND: Cervical dysplasia and tumorigenesis have been linked with numerous chromosomal aberrations. The goal of this study was to evaluate 35 genomic regions associated with cervical disease and to select those which were found to have the highest frequency of aberration for use as probes in fluorescent in-situ hybridization. METHODS: The frequency of gains and losses using fluorescence in-situ hybridization were assessed in these 35 regions on 30 paraffin-embedded cervical biopsy specimens. Based on this assessment, 6 candidate fluorescently labeled probes (8q24, Xp22, 20q13, 3p14, 3q26, CEP15) were selected for additional testing on a set of 106 cervical biopsy specimens diagnosed as Normal, CIN1, CIN2, CIN3, and SCC. The data were analyzed on the basis of signal mean, % change of signal mean between histological categories, and % positivity. RESULTS: The study revealed that the chromosomal regions with the highest frequency of copy number gains and highest combined sensitivity and specificity in high-grade cervical disease were 8q24 and 3q26. The cytological application of these two probes was then evaluated on 118 ThinPrep samples diagnosed as Normal, ASCUS, LSIL, HSIL and Cancer to determine utility as a tool for less invasive screening. Using gains of either 8q24 or 3q26 as a positivity criterion yielded specificity (Normal +LSIL+ASCUS) of 81.0% and sensitivity (HSIL+Cancer) of 92.3% based on a threshold of 4 positive cells. CONCLUSIONS: The application of a FISH assay comprised of chromosomal probes 8q24 and 3q26 to cervical cytology specimens confirms the positive correlation between increasing dysplasia and copy gains and shows promise as a marker in cervical disease progression.

Clinical and Educational Gaps in Diagnosis of Nail Disorders.

Dermatologists care for skin, hair, and nails, yet many dermatologists find nail disorders challenging. Practice gaps in knowledge, skill, and attitude in clinical practice and resident education are sometimes impediments to timely medical and surgical diagnosis of nail disorders. Limited resident exposure to diagnosis and management of complicated nail disorders and lack of experience performing diagnostic and surgical procedures impairs progress toward surmounting these gaps.

Religious Beliefs and Depression: Psychosocial Factors Affecting HIV Treatment Outcomes in South Africa.

Analyzing factors associated with virological failure (VF) may improve antiretroviral therapy (ART) outcomes for individuals living with HIV. The Risk Factors for Virological Failure (RFVF) study compared 158 cases with VF (viral load, VL, >1,000 copies/mL) and 300 controls with virological suppression (VL ≤1,000 copies/mL) after ≥5 months on their first ART regimen at McCord Hospital in Durban, South Africa between October 2010 and June 2012. RFVF participants completed a battery of various psychosocial measures. Using multivariate logistic regression stratified for gender, the association of various psychosocial factors with VF was assessed. It was found that not all factors were equally significant for both genders. The factors that were significantly associated with VF for both genders were younger age, shorter treatment duration and reporting depressive symptoms. The factors associated with VF that differed by gender were religious inactivity, having HIV+ family members, and status disclosure to friends.

The combination of pill count and self-reported adherence is a strong predictor of first-line ART failure for adults in South Africa.

BACKGROUND: Suboptimal adherence to antiretroviral therapy (ART) is a strong predictor of virologic failure (VF) among people with HIV. Various methods such as patient self-report, pill counts and pharmacy refills have been utilized to monitor adherence. However, there are limited data on the accuracy of combining methods to better predict VF in routine clinical settings. We examined various methods to assess adherence including pill count, medication possession ratio (MPR), and self-reported adherence in order to determine which was most highly associated with VF after > 6 months on ART. METHODS: We conducted a secondary analysis of data from a case-control study. At enrollment, pharmacy refill data were collected retrospectively from the medical chart, pill counts were completed to derive a pill count adherence ratio (PCAR) and a self-report questionnaire was administered to all participants. Parametric smooth splines and receiver operator characteristic (ROC) analyses were carried out to assess the accuracy of the adherence methods. RESULTS: 458 patients were enrolled from October 2010 to June 2012. Of these, 158 (34.50%) experienced VF (cases) and 300 (65.50%) were controls. The median (IQR) PCAR was 1.10 (0.99-1.14) for cases and 1.13 (1.08-1.18) for controls (p < 0.0001). The median MPR was 1.00 (0.97-1.07) for cases and 1.03 (0.96-1.07) for controls (p = 0.83). Combination of PCAR and self-reported questions was highly associated with VF. CONCLUSION: In this setting, a combination of pill count adherence and self-report adherence questions had the highest diagnostic accuracy for VF. Further validation of this simple, low-cost combination is warranted in large prospective studies.

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.

Treating cosmetically induced nail problems.

Smooth, lustrous nails are a sign of health and beauty in our society and fuel the US$6-billion nail salon industry in the United States. Although many women can use nail cosmetics without adverse consequences, when problems occur it is important to recognize the causes and treat the problem condition. The cornerstone of management of nail cosmetic problems is prevention through education. In spite of efforts to that end, nail salon procedures and materials can cause nail disease that must be recognized and treated in order to restore the nails to health.

Gene copy mapping of the ERBB2/TOP2A region in breast cancer.

ERBB2 is one of the most important oncogenes in breast cancer, and its disordered expression is commonly associated with gene amplification. Amplification of at least one gene near ERBB2, topoisomerase IIalpha (TOP2A), has been shown to be clinically significant, but the prevailing patterns of gene amplification in this region of chromosome arm 17q have not been studied systematically in clinical cases of breast cancer. For characterizing this region, a commercial ERBB2-containing contig probe and 7 probes prepared from single overlapping BAC and P1 clones lying telomeric to ERBB2 and including TOP2A were hybridized to 77 ERBB2-amplified archival breast tumor specimens from 75 patients. The 7 single-clone probes covered a region of approximately 650 kb starting 114 kb telomeric to ERBB2. Amplification of the ERBB2 contig target alone was found in 32% of the tumors, whereas all 8 probe targets were amplified in 12% of the tumors, based on an amplification criterion of there being more than or equal to 2 targets per chromosome 17 centromere. When one of the 7 overlapping probes encompassing TOP2A indicated amplification within a specimen, all probes telomeric to that probe usually showed amplification. Only 5 specimens had regions of normal or deleted targets separating 2 amplified targets. Also, tumors that showed deletion of TOP2A usually showed deletion of one or more contiguous targets. The observed patterns of amplification and deletion are consistent with the break-fusion-bridge model for gene amplification. TOP2A was amplified in 25% of all tumor specimens and was deleted in 24%, based on a deletion criterion of there being fewer than or equal to 0.75 targets per chromosome 17 centromere. Considering the relevance of the TOP2A gene product to anthracycline therapy and the wealth of other cancer-associated genes within the ERBB2/TOP2A region, the pattern of amplification and deletion near ERBB2 and TOP2A may have a dramatic effect on the malignant potential of breast carcinomas and their response to therapy.

A fluorescence in situ hybridization-based assay for improved detection of lung cancer cells in bronchial washing specimens.

BACKGROUND: Interphase fluorescence in situ hybridization (FISH) is a powerful tool for detecting chromosome and locus-specific changes in tumor cells. We developed a FISH-based assay to detect genetic changes in bronchial washing specimens of lung carcinoma patients. METHODS: The assay uses a mixture of fluorescently labeled probes to the centromeric region of chromosome 1 and to the 5p15, 8q24 (site of the c-myc gene), and 7p12 (site of the EGFR gene) loci to assess cells in bronchial washing specimens for chromosomal abnormalities indicative of lung carcinoma. The FISH assay was performed on 74 specimens that had been assessed previously for evidence of malignancy by routine cytology with Pap staining. RESULTS: Forty-eight patients had histologically confirmed lung carcinoma and 26 patients had a clinical diagnosis that was negative for lung carcinoma. FISH analysis was performed without knowledge of the patient's clinical information. The finding of six or more epithelial cells with gains of two or more chromosome regions was considered a positive FISH result (i.e., evidence of malignancy). The sensitivity of FISH for the detection of lung carcinoma was 82% in this set of specimens compared with a 54% sensitivity by design for cytology (FISH vs. cytology, P = 0.007). FISH detected 15 of 18 specimens that were falsely negative by cytology. The specificities of FISH and cytology were 82% and 100%, respectively, and were not significantly different (P = 0.993). CONCLUSIONS: The data indicate a potential utility of the FISH assay as an adjunct to bronchial washing cytology in routine clinical practice.