HIV-1 antiretroviral drug resistance patterns in patients failing NNRTI-based treatment: results from a national survey in South Africa.

BACKGROUND: Routine HIV-1 antiretroviral drug resistance testing for patients failing NNRTI-based regimens is not recommended in resource-limited settings. Therefore, surveys are required to monitor resistance profiles in patients failing ART. METHODS: A cross-sectional survey was conducted amongst patients failing NNRTI-based regimens in the public sector throughout South Africa. Virological failure was defined as two consecutive HIV-1 viral load results >1000 RNA copies/mL. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to Stanford HIVdb v7.0.1. RESULTS: A total of 788 sequences were available for analysis. Most patients failed a tenofovir-based NRTI backbone (74.4%) in combination with efavirenz (82.1%) after median treatment duration of 36 months. K103N (48.9%) and V106M (34.9%) were the most common NNRTI mutations. Only one-third of patients retained full susceptibility to second-generation NNRTIs such as etravirine (36.5%) and rilpivirine (27.3%). After M184V/I (82.7%), K65R was the most common NRTI mutation (45.8%). The prevalence of K65R increased to 57.5% in patients failing a tenofovir regimen without prior stavudine exposure. Cross-resistance to NRTIs was often observed, but did not seem to affect the predicted activity of zidovudine as 82.9% of patients remained fully susceptible to this drug. CONCLUSIONS: The introduction of tenofovir-based first-line regimens has dramatically increased the prevalence of K65R mutations in the HIV-1-infected South African population. However, most patients failing tenofovir-based regimens remained fully susceptible to zidovudine. Based on these data, there is currently no need to change either the recommended first- or second-line ART regimens in South Africa.

Prevalence of Antiretroviral Drug Resistance in Patients Who Are Not Responding to Protease Inhibitor-Based Treatment: Results From the First National Survey in South Africa.

Limited data exist on human immunodeficiency virus type 1 (HIV-1) resistance in patients who are not responding to protease inhibitor (PI)-based regimens in resource-limited settings. This study assessed resistance profiles in adults across South Africa who were not responding to PI-based regimens. pol sequencing was undertaken and submitted to the Stanford HIV Drug Resistance Database. At least 1 major PI mutation was detected in 16.4% of 350 participants. A total of 53.4% showed intermediate resistance to darunavir/ritonavir, whereas high-level resistance was not observed. Only 5.2% and 32.8% of participants showed high-level and intermediate resistance to etravirine, respectively. Although the prevalence of major PI mutations was within previously reported ranges, most patients will likely experience virological suppression during receipt of currently available South African third-line regimens.

Predicting Cereal Root Disease in Western Australia Using Soil DNA and Environmental Parameters.

Root diseases have long been prevalent in Australian grain-growing regions, and most management decisions to reduce the risk of yield loss need to be implemented before the crop is sown. The levels of pathogens that cause the major root diseases can be measured using DNA-based services such as PreDicta B. Although these pathogens are often studied individually, in the field they often occur as mixed populations and their combined effect on crop production is likely to vary across diverse cropping environments. A 3-year survey was conducted covering most cropping regions in Western Australia, utilizing PreDicta B to determine soilborne pathogen levels and visual assessments to score root health and incidence of individual crop root diseases caused by the major root pathogens, including Rhizoctonia solani (anastomosis group [AG]-8), Gaeumannomyces graminis var. tritici (take-all), Fusarium pseudograminearum, and Pratylenchus spp. (root-lesion nematodes) on wheat roots for 115, 50, and 94 fields during 2010, 2011, and 2012, respectively. A predictive model was developed for root health utilizing autumn and summer rainfall and soil temperature parameters. The model showed that pathogen DNA explained 16, 5, and 2% of the variation in root health whereas environmental parameters explained 22, 11, and 1% of the variation in 2010, 2011, and 2012, respectively. Results showed that R. solani AG-8 soil pathogen DNA, environmental soil temperature, and rainfall parameters explained most of the variation in the root health. This research shows that interactions between environment and pathogen levels before seeding can be utilized in predictive models to improve assessment of risk from root diseases to assist growers to plan more profitable cropping programs.

First Report of Stem Rot in Canola Caused by Sclerotinia minor in Western Australia.

Canola (Brassica napus L.) is a significant oilseed break crop in Western Australia. In late October 2012, canola plants (cv. Jackpot) showing typical symptoms of stem rot with bleached appearance and fluffy white fungal growth on the infected tissues were observed in an experimental plot at Katanning, Western Australia. Severely affected plants were lodged with partially filled pods and shriveled seeds. Small, irregular sclerotia (<2 mm) were found inside the plants and were more concentrated in the root and basal stem than in the upper stem regions. Ten sclerotia from three symptomatic plants were surface sterilized with 1.25% NaOCl for 1 minute, rinsed twice in sterile distilled water and plated on potato dextrose agar (PDA) supplemented with 10 mg liter-1 Aureomycin. Plates were incubated under a black light at 22 ± 2°C. Sclerotinia minor Jagger was consistently isolated as identified by colony morphology, abundant sclerotia on PDA, and size of sclerotia <2 mm (3). A pathogenicity test was conducted on six 7-week-old canola plants cv. Tawriffic. Mycelial plugs (5 mm diameter) were excised from the margins of actively growing 3-day-old cultures and attached on to the 2nd and the 4th internodes of the main stem with Parafilm. Three plants inoculated with agar plugs without mycelium served as controls. Following inoculation, the plants were kept in a misting chamber for 48 h and then transferred to a growth room at 18 ± 2°C with a 12-h photoperiod. Typical lesions of stem rot similar to those observed in the field were noticed 3 days after inoculation. Within a week, all the inoculated plants were completely girdled by the lesions with stems breaking off and collapsing at the point of inoculation. Small sclerotia formed within lesions on the outside of the diseased stems. S. minor was reisolated from the stems of symptomatic plants, fulfilling Koch's postulates. No symptoms developed on the control plants. S. minor has previously been reported on host plants other than canola in Western Australia (4), canola petals in New South Wales, Australia (2), and also on canola stems in Argentina (1). To our knowledge, this is the first report of occurrence of S. minor on canola in Western Australia. Although S. sclerotiorum is the predominant species causing stem rot in canola in Western Australia, S. minor has the potential to cause significant yield losses under favorable environmental conditions. Correct identification and monitoring a shift in pathogens is essential for implementing effective management strategies and breeding resistant varieties. References: (1) S. A. Gaetán et al. Plant Dis. 92:172, 2008. (2) T. Hind-Lanoiselet et al. Aust Plant Pathol. 30:289, 2001. (3) L. M. Kohn. Phytopathology 69:881, 1979. (4) R. Shivas. J. Royal. Soc. Western Australia 72:1, 1989.

Accidental death and the rule of joint and several liability.

Most U.S. states have enacted JSL reform, the move from a regime of joint and several liability (JSL) that allows plaintiffs to claim full recovery from any one of multiple defendants to one where defendants are held liable only for the harm they cause. Contrary to previous theoretical work, we show that JSL reform can increase precaution by judgment proof agent by giving "deep pockets" an incentive to reduce their own liability by bringing judgment-proof agents into court. This result can help explain our empirical findings showing that JSL reform reduces death rates (and hence increase precaution) for many types of accidents. Together, these results highlight the role that litigation costs and judgment-proof agents play in the functioning of the American tort system.

UNDERSTANDING DOCTOR DECISION MAKING: THE CASE OF DEPRESSION TREATMENT.

Treatment for depression is complex, requiring decisions that may involve trade-offs between exploiting treatments with the highest expected value and experimenting with treatments with higher possible payoffs. Using patient claims data, we show that among skilled doctors, using a broader portfolio of drugs predicts better patient outcomes, except in cases where doctors' decisions violate loose professional guidelines. We introduce a behavioral model of decision making guided by our empirical observations. The model's novel feature is that the trade-off between exploitation and experimentation depends on the doctor's diagnostic skill. The model predicts that higher diagnostic skill leads to greater diversity in drug choice and better matching of drugs to patients even among doctors with the same initial beliefs regarding drug effectiveness. Consistent with the finding that guideline violations predict poorer patient outcomes, simulations of the model suggest that increasing the number of possible drug choices can lower performance.

Asymptomatic Bordetella pertussis infections in young African infants and their mothers identified within a longitudinal cohort.

Despite long-standing vaccination programs, pertussis incidence has increased in numerous countries; transmission by asymptomatic individuals is a suspected driver of this resurgence. However, unequivocal evidence documenting asymptomatic infections in adults and children is lacking due, in part, to the cross-sectional nature of most pertussis surveillance studies. In addition, modern pertussis surveillance relies on quantitative PCR (qPCR) using fixed diagnostic thresholds to identify cases. To address this gap, we present a longitudinal analysis of 17,442 nasopharyngeal samples collected from a cohort of 1,320 Zambian mother/infant pairs. Using full-range cycle threshold (CT) values from IS481 qPCR assays, we document widespread asymptomatic infections among mothers and also, surprisingly, among young infants. From an initial group of eight symptomatic infants who tested positive by qPCR, we identify frequent contemporaneous subclinical infections in mothers. Within the full cohort, we observe strong temporal correlation between low- and high-intensity qPCR signals. We compute a single time-averaged score for each individual summarizing the evidence for pertussis infection (EFI), and show that EFI strongly clusters within mother/infant pairs, and is strongly associated with clinical symptomatology and antibiotic use. Overall, the burden of pertussis here is substantially underestimated when restricting diagnostic criteria to IS481 CT≤35. Rather, we find that full-range CT values provide valuable insights into pertussis epidemiology in this population, and illuminate the infection arc within individuals. These findings have significant implications for quantifying asymptomatic pertussis prevalence and its contribution to overall transmission. Our results also expose limitations of threshold-based interpretations of qPCR assays in infectious disease surveillance.

The use of near peer teachers in the radiography program at Monash University.

INTRODUCTION: This research investigated the perceptions of fourth year students as near peer (NP) teachers, and second year NP learners during a pathology unit in the Bachelor of Medical Imaging and Radiation Sciences at Monash University. METHODS: A systematic review of literature was undertaken to inform the research design. Semi-structure pre- and post-teaching interviews were conducted with four NP teachers. An online survey was conducted with 50 second year NP learners. Quantitative data was analysed using Microsoft Excel. Interview data and 64 free text comments in the online survey were analysed using NVivo. RESULTS: NP students felt there were significant benefits being involved in the NP program, including an explanation of concepts and complementary teaching to lecturers. Three of the free text comments outlined a negative perception, although in each case the comment related to the student's individual learning style rather than being negative against the program. CONCLUSION: The benefits to learners in a pathology course was consistent to those identified within the literature. Students perceived benefits in terms of content delivery, interaction and communication. Recommendations were made about the organisation and design for future cohorts.

Effect of presumptive co-trimoxazole prophylaxis on pneumococcal colonization rates, seroepidemiology and antibiotic resistance in Zambian infants: a longitudinal cohort study.

OBJECTIVE: To ascertain the microbiological consequences of WHO's recommendation for presumptive co-trimoxazole prophylaxis for infants with perinatal HIV exposure. METHODS: Using a longitudinal cohort design, we followed HIV-exposed and HIV-unexposed infants trimonthly for up to 18 months per infant. HIV-exposed infants received daily co-trimoxazole prophylaxis from 6 weeks to > or = 12 months of age. Using Streptococcus pneumoniae as our sentinel pathogen, we measured how co-trimoxazole altered nasopharyngeal colonization, pneumococcal resistance to antibiotics and serotype distribution as a function of co-trimoxazole exposure. FINDINGS: From 260 infants followed for 3096 patient-months, we detected pneumococci in 360/1394 (25.8%) samples. HIV-exposed infants were colonized more frequently than HIV-unexposed infants (risk ratio, RR: 1.4; 95% confidence interval, CI: 1.0-1.9, P = 0.04). Co-trimoxazole prophylaxis reduced colonization by ca 7% but increased the risk of colonization with co-trimoxazole-resistant pneumococci within 6 weeks of starting prophylaxis (RR: 3.2; 95% CI: 1.3-7.8, P = 0.04). Prophylaxis with co-trimoxazole led to a small but statistically significant increase of nasopharyngeal colonization with pneumococci not susceptible to clindamycin (RR: 1.6; 95% CI: 1.0-2.6, P = 0.04) but did not increase the risk of non-susceptibility to penicillin (RR: 1.1; 95% CI: 0.7-1.7), erythromycin (RR: 1.0; 95% CI: 0.6-1.7), tetracycline (RR: 0.9; 95% CI: 0.6-1.5) or chloramphenicol (RR: 0.8; 95% CI: 0.3-2.3). Co-trimoxazole prophylaxis did not cause the prevailing pneumococcal serotypes to differ from those that are targeted by the 7-valent conjugate pneumococcal vaccine (RR: 1.0; 95% CI: 0.7-1.6). CONCLUSION: Co-trimoxazole prophylaxis modestly suppresses pneumococcal colonization but accelerates infant acquisition of co-trimoxazole- and clindamycin-resistant pneumococci. Co-trimoxazole prophylaxis appears unlikely to compromise the future efficacy of conjugate vaccines.

Diagnosing Expertise: Human Capital, Decision Making, and Performance among Physicians.

Expert performance is often evaluated assuming that good experts have good outcomes. We examine expertise in medicine and develop a model that allows for two dimensions of physician performance: decision making and procedural skill. Better procedural skill increases the use of intensive procedures for everyone, while better decision making results in a reallocation of procedures from fewer low-risk to high-risk cases. We show that poor diagnosticians can be identified using administrative data and that improving decision making improves birth outcomes by reducing C-section rates at the bottom of the risk distribution and increasing them at the top of the distribution.

Provider practice style and patient health outcomes: The case of heart attacks.

When a patient arrives at the Emergency Room with acute myocardial infarction (AMI), the provider on duty must quickly decide how aggressively the patient should be treated. Using Florida data on all such patients from 1992 to 2014, we decompose practice style into two components: The provider's probability of conducting invasive procedures on the average patient (which we characterize as aggressiveness), and the responsiveness of the choice of procedure to the patient's characteristics. We show that within hospitals and years, patients with more aggressive providers have consistently higher costs and better outcomes. Since all patients benefit from higher utilization of invasive procedures, targeting procedure use to the most appropriate patients benefits these patients at the expense of the less appropriate patients. We also find that the most aggressive and responsive physicians are young, male, and trained in top 20 schools.

Torts, expertise, and authority: liability of physicians and managed care organizations.

We examine optimal individual and entity-level liability for negligence when expected accident costs depend on both the agent's level of expertise and the principal's level of authority. We consider these issues in the context of physician and managed care organization (MCO) liability for medical malpractice. Under current law, physicians generally are considered independent contractors and hence MCOs are not liable for negligent acts by physicians. We find that the practice of reviewing the medical decisions of physicians affects their incentives to take care, which in turn implies that it is efficient for MCOs to be held liable for the torts committed by their physicians.

Sporadic non-A, non-B hepatitis and Epstein-Barr hepatitis associated with the Guillain-Barré syndrome.

Three cases of Guillain-Barré syndrome (GBS) complicating sporadic non-A, non-B viral hepatitis (NANB) are reported. One case occurred in the incubation period for NANB hepatitis, and the other cases were noted to have hepatitis at the time of hospital admission due to paralysis. Three patients (13%) in a prospective series of 23 patients with GBS were found to have subclinical hepatitis (two patients with NANB hepatitis, and one patient with Epstein-Barr viral hepatitis). This unexpectedly high incidence of hepatitis associated with GBS is discussed and a possible causal link between NANB hepatitis and surgery-related GBS is proposed.

Repeater F waves: a comparison of sensitivity with sensory antidromic wrist-to-palm latency and distal motor latency in the diagnosis of carpal tunnel syndrome.

Thirty-five thousand six hundred supramaximal shocks were applied to 209 healthy and 147 entrapped median nerves (carpal tunnel syndrome--CTS) to characterize the backfiring behavior of the alpha motor neuron pool of abductor pollicis brevis in health and the modifying effect of a compressive neuropathy. A contraction of the normal subpopulation of active F-wave generators was found in CTS, while active neurons backfired at higher than normal frequencies (p less than 0.001). These modifications in spinal behavior are reflected in the % Repeater F-wave value, whose sensitivity in the detection of CTS approaches that of sensory wrist-to-palm latency estimation. This technique offers an alternative to latency measurement in the diagnosis of CTS. An economical strategy for the electrodiagnosis of CTS is proposed.

Electrophysiologic studies in Miller Fisher syndrome.

Serial peripheral nerve conduction studies are reported on a case of acute ophthalmoplegia and ataxia with areflexia (Miller Fisher syndrome). These tests showed abnormalities identical to those found in the Guillain-Barré syndrome.

Incidence and predictors of surgical-site infections in Vietnam.

OBJECTIVE: To determine the incidence of, and risk factors for, surgical-site infections (SSIs). DESIGN: Prospective observational study of all patients undergoing surgery during a 3-month period. SETTING: Two urban hospitals in Hanoi, Vietnam. PATIENTS: All 697 patients admitted for emergent and elective surgery. METHODS: Data were collected on all patients undergoing surgery during a 3-month period at each hospital. We stratified the data by type of surgery, wound class, and Study on the Efficacy of Nosocomial Infection Control (SENIC) risk index. The analysis was done with the data sets from each hospital separately and with the combined data. The risk factors for SSI were identified using a logistic-regression model. RESULTS: During the period of observation, 10.9% of 697 patients had SSI. The SSI rate was 8.3% for clean wounds, 8.6% for clean-contaminated, 12.2% for contaminated, and 43.9% for dirty wounds. The lowest rate of SSI (2.4%) was found in obstetric-gynecologic procedures and the highest rate (33.3%) in cardiothoracic operations. Using the SENIC risk index, the incidence of SSI in low-risk patients was 5.1%; for medium-risk patients, 13.5%, and high-risk patients, 24.2%. In a logistic-regression model, abdominal surgery (odds ratio [OR], 4.46; P<.01) and wound class IV (OR, 5.67; P<.01) were significant predictors of SSI. All patients were treated with prolonged courses of perioperative antibiotics. Overall infection control practices were poor as a result of deficient facilities, limited surgical instruments, and a lack of proper supplies for wound care and personal hygiene. CONCLUSIONS: There was a higher incidence of SSI in low-risk patients in Vietnam compared with developed countries. Excessive reliance on antimicrobial therapy as a means to limit SSI places patients at higher risk of adverse effects from treatment and also may contribute to worsening problems with antimicrobial resistance. Establishment of an infection control program with guidelines for antimicrobial use should improve the use of prophylactic antibiotics and attention to proper surgical and wound-care techniques. These interventions also should reduce the incidence of SSI and its associated morbidity and costs.

A method for finding stereotaxic coordinates from brain sections.

A method for finding the stereotaxic coordinates of brain areas from actual brain sections is presented. It uses a digitizer connected to a computer to gather coordinates from photographs of brain sections. The coordinates are mathematically translated and rotated to yield stereotaxic atlas coordinates of the areas digitized.

Age, temperature, and parasitaemia predict chloroquine treatment failure and anaemia in children with uncomplicated Plasmodium falciparum malaria.

The prevalence of chloroquine-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa and parts of South America over the last 2 decades, and has been associated with increased anaemia-associated morbidity and higher mortality rates. Prospectively collected clinical and parasitological data from a multicentre study of 788 children aged 6-59 months with uncomplicated P. falciparum malaria were analysed in order to identify risk factors for chloroquine treatment failure and to assess its impact on anaemia after therapy. The proportion of chloroquine treatment failures (combined early and late treatment failures) was higher in the central-eastern African countries (Tanzania, 53%; Uganda, 80%; Zambia, 57%) and Ecuador (54%) than in Ghana (36%). Using logistic regression, predictors of early treatment failure included younger age, higher baseline temperature, and greater levels of parasitaemia. We conclude that younger age, higher initial temperature, and higher baseline parasitaemia predict early treatment failure and a higher probability of worsening anaemia between admission and days 7 or 14 post-treatment.

Restoration of the shutter mechanism in inguinal herniorrhaphy.

A technique of inguinal herniorrhaphy that restores the normal shutter mechanism at the internal ring by completing the lateral portion of the repair anterior to the cord is described. We believe that this technique will decrease the incidence of recurrent hernia.

Recovery of visual field constriction following discontinuation of vigabatrin.

Epilepsy patients treated with vigabatrin may develop symptomatic or asymptomatic concentric visual field constriction due to GABA-associated retinal dysfunction. The prevalence and course of this side effect are not established yet; in previously reported adult patients the visual disturbances seem to be irreversible. We present two patients with a significant improvement of visual field constriction and retinal function after the discontinuation of vigabatrin. These findings suggest that vigabatrin-associated retinal changes are at least partly reversible in some patients, and that these patients may benefit significantly from a withdrawal of vigabatrin. Larger scale clinical studies are needed to identify predictive factors both for the occurrence and reversibility of vigabatrin-associated visual field defects.