Heart Failure Among Patients with Multiple Myeloma Treated with Carfilzomib-Based Versus Non-Carfilzomib-Based Regimens in the United States by Race.

BACKGROUND: Carfilzomib treatment for multiple myeloma (MM) can increase heart failure risk. Whether this risk differs by race is unknown. PATIENTS AND METHODS: We sought to estimate the incidence rates (IRs) of heart failure hospitalization among mostly 65-years-and-older US patients with MM by race treated with carfilzomib- and non-carfilzomib-based regimens in the real-world using Centers for Medicare & Medicaid Services Medicare Fee-for-Service data, Optum Clinformatics Data Mart, and Humana Research Database. The risk of heart failure hospitalization associated with a carfilzomib-based regimen was evaluated using propensity score matching among Black and White patients receiving second or later lines of therapy. RESULTS: Most patient-episodes (88%) were in persons 65 years or older for the 3 cohorts combined. The IR (95% CI) of heart failure hospitalization was higher for patient-episodes treated with a carfilzomib-based regimen than those with a non-carfilzomib-based regimen for both White (14.5 [12.2-17.0] vs. 10.7 [10.3-11.2] events per person-years) and Black patients (15.8 [10.1-23.5] vs. 12.1 [10.9-13.4] events per person-years) in the Medicare cohort. After propensity score matching, the hazard ratio (95% CI) of increased heart failure hospitalization comparing carfilzomib-based to non-carfilzomib-based regimens for White patients (1.6 [1.3-2.0]) was similar to that of Black patients (1.7 [1.0-2.9]) in the Medicare Database, and in the Humana Database (1.4 [0.8-2.6] and 1.2 [0.4-3.5], respectively). CONCLUSION: Although the IR of heart failure among patients with MM treated with a carfilzomib-based regimen was slightly higher, no evidence suggested the relative risk was different between White and Black patients with MM.

Navigating metastatic colorectal treatment options in the USA: a survey of patient acceptance of skin toxicities associated with Vectibix.

PURPOSE: To understand the extent to which metastatic colorectal cancer (mCRC) patients receive education on the prevention and management associated with skin rash following Vectibix treatment. Furthermore, to investigate how this adverse event affects a patient's quality of life (QoL) and influences their treatment decisions. METHODS: A cross-sectional survey was administered to 200 mCRC patients (100 Vectibix users and 100 Vectibix non-users). After excluding respondents who had used cetuximab, 61 Vectibix users and 56 Vectibix non-users remained. RESULTS: Most Vectibix users (79%) experienced a skin rash in response to treatment of which 65% considered the rash moderate, 27% mild, and 8% severe. Vectibix users generally felt they were adequately informed about the rash (83%), with the most common messages received related to sun protection. However, sunscreen was used by only 42% of patients prior to rash and 60% of patients following the appearance of rash. The use of oral antibiotics was low prior to rash (21%) and following rash (46%). Among patients experiencing a rash within the past week (n=16), 75% reported the rash had a large negative impact on their QoL based on the Dermatology Life Quality Index. CONCLUSION: There was a disconnect between patients feeling they were adequately informed and use of prevention and management strategies such as sun protection. This suggests a gap in patient education and adoption currently exists on management strategies both prior to and following the appearance of rash. Given the negative impact that skin toxicity has on the patient's quality of life, it is essential that patients receive and subsequently utilize all information that can minimize rash severity.

An evaluation of RAS testing among metastatic colorectal cancer patients in the USA.

Background: Data on RAS testing practices prior to metastatic colorectal cancer (mCRC) treatment initiation are lacking in the USA. Materials & methods: Flatiron data were utilized for patients diagnosed with mCRC between 2011 and 2017. Flatiron is a longitudinal, demographically and geographically diverse database representing data from over 1.5 million active US patients treated at 255 community and hospital-affiliated oncology clinics. Results: Among 17,387 mCRC patients 69% were RAS tested and 31% were never tested. Timing of RAS testing was as follows: 23% were tested at the time of their initial CRC diagnosis, 60% following mCRC diagnosis but prior to first line of treatment, 3% prior to third line, the remaining 14% were tested following third line. Conclusion: A third (31%) of patients failed to receive RAS testing, therefore all treatment options were unavailable to them. These data highlight how universal testing has not been achieved.

Occurrence and Management of Thrombocytopenia in Metastatic Colorectal Cancer Patients Receiving Chemotherapy: Secondary Analysis of Data From Prospective Clinical Trials.

INTRODUCTION: Chemotherapy-induced thrombocytopenia (CIT) contributes to treatment dose delay and/or modification, often resulting in poorer survival and disease progression. We explored the incidence and clinical consequences of CIT among metastatic colorectal cancer (mCRC) patients. MATERIALS AND METHODS: Data from two prospective randomized phase 3 trials of mCRC patients receiving either first-line FOLFOX4 (fluorouracil, leucovorin, oxaliplatin) or second-line FOLFIRI (fluorouracil, leucovorin, irinotecan) were analyzed. Thrombocytopenia was defined by platelet count < 100 × 109/L (further categorized by grade) and by recorded adverse events (AEs). Co-occurrence of anemia (hemoglobin < 12 g/dL) and neutropenia (neutrophil count < 2 × 109/L) and clinical consequences of CIT were also evaluated. RESULTS: Among 1078 mCRC patients in the FOLFOX4 study, cumulative incidence of CIT based on platelet count was 37% (grade 3, 2%; grade 4, 1%) during an average 8 months' follow-up. Neutropenia or anemia were absent in 44% of CIT episodes; 62% of CIT AEs led to chemotherapy dose delay, change, and/or discontinuation. Among 1067 mCRC patients in the FOLFIRI study, cumulative incidence of CIT based on platelet count was 4% (grade 3, < 1%; grade 4, 0) during an average 4 months' follow-up. Neutropenia or anemia were absent in 22% of CIT episodes; 32% of CIT AEs led to chemotherapy dose delay, change, and/or discontinuation. With both regimens, transfusions and hospitalizations after CIT AEs were rare (< 3%). CONCLUSION: CIT was common among mCRC patients receiving the FOLFOX4 regimen. The most frequent consequence of CIT was a delay in chemotherapy, highlighting the unmet need in CIT management.

A Systematic Literature Review and Meta-Analysis Describing the Prevalence of KRAS, NRAS, and BRAF Gene Mutations in Metastatic Colorectal Cancer.

BACKGROUND: Tumors of the metastatic colorectal cancer (mCRC) patients that are wildtype (WT) for KRAS or NRAS mutations respond more favorably to anti-epidermal growth factor receptor (EGFR) treatments. Treatment guidelines now recommend that all mCRC patients have WT KRAS and NRAS tumor status confirmed prior to initiating anti-EGFR therapy. Evidence also suggests that BRAF mutations may predict lack of response to anti-EGFR therapy. As such, there is now a need for comprehensive data on the prevalence of KRAS, NRAS, and BRAF mutations among patients with mCRC. METHODS: A systematic literature review was conducted among studies that described the prevalence of KRAS, NRAS, and BRAF gene mutations in mCRC patients. Observational cohort studies and standard of care arm of randomized clinical trials were included. Random effects meta-analysis models were used to create summary prevalence estimates for each of the mutation types. Subgroup analyses were also conducted to identify potential sources of heterogeneity. Exploratory analyses of overall and progression-free survival by mutation status were also conducted. RESULTS: This systematic review and meta-analysis included 275 studies comprising 77,104 mCRC patients. The summary prevalence estimate was 35.9% for KRAS mutations, 7.1% for BRAF mutations, and 4.1% for NRAS mutations. Female patients had significantly more KRAS and BRAF mutations than males, and significant variation by study location was observed for both KRAS and BRAF mutation prevalence. Overall survival was significantly decreased for patients with KRAS, BRAF, and NRAS mutations compared to those with WT tumors. Progression-free survival was also significantly decreased among patients with KRAS and BRAF mutations. CONCLUSIONS: KRAS, NRAS, and BRAF mutation statuses in patients with mCRC are important predictors of treatment success and may also have prognostic value. In this paper we present the first systematic and comprehensive literature review and meta-analysis of the prevalence of KRAS, BRAF, and NRAS mutations and demonstrate the prognostic impact of mutation status on survival.

A Multinational Assessment of Gastric, Esophageal, and Colorectal Cancer Burden: A Report of Disease Incidence, Prevalence, and Fatality.

INTRODUCTION: Digestive cancers, including colorectal, stomach, and esophageal cancer, represent one-third of all new cancer cases in the world. This comprehensive analysis seeks to summarize the burden of digestive system cancers on a global scale, within specific countries in the Americas, Europe, Asia, Oceania, and Africa. METHODS: Burden is measured using prevalence, incidence, and case-fatality rates. Estimates of incidence rates and case-fatality ratios were further stratified by gender and age group (< 65 years and ≥ 65 years). RESULTS: In general, these data highlight differences in the prevalence and incidence of gastric, esophageal, and colorectal cancers by gender and region. Large variations in case-fatality rates by gender and age are also present. CONCLUSIONS: These data illustrate the worldwide burden of digestive diseases and may help guide resource allocation to decrease the impact of digestive cancers around the world.

Prevalence of RAS and BRAF mutations in metastatic colorectal cancer patients by tumor sidedness: A systematic review and meta-analysis.

Studies have shown that the prevalence of RAS and BRAF mutations may differ by tumor sidedness among metastatic colorectal cancer (mCRC) patients. Both mutation status and tumor sidedness may impact survival and disease progression and RAS mutation status has been shown to predict response to anti-epidermal growth factor receptor (EGFR) therapy. A systematic literature review and meta-analysis were conducted to estimate the pooled prevalence of RAS and BRAF mutations by tumor sidedness in studies of mCRC patients. Forty-four studies comprising 15 981 mCRC patients tested for RAS and/or BRAF mutations were included in the meta-analyses. The prevalence of RAS mutations differed significantly by tumor side (32.4% among left-sided tumors, 41.3% among right-sided tumors; P = .017), as did the prevalence of KRAS mutations (35.8% among left-sided tumors, 46.3% among right-sided tumors; P < .0001) and BRAF mutations (4.3% among left-sided tumors, 16.3% among right-sided tumors; P < .0001). Among right-sided tumors, the prevalence of RAS and KRAS mutations varied significantly by study design, with higher prevalence among observational studies than clinical trials, and there was significant variation by study location for the prevalence of KRAS mutations in left-sided tumors and the prevalence of BRAF mutations in right-sided tumors. These results help to better characterize the mCRC population to better inform clinicians and researchers. Few of the included studies reported overall or progression-free survival (PFS) by both tumor sidedness and mutation status. As both of these factors may have prognostic impact, future studies should consider evaluating survival by these variables.

The incidence of infusion reactions associated with monoclonal antibody drugs targeting the epidermal growth factor receptor in metastatic colorectal cancer patients: A systematic literature review and meta-analysis of patient and study characteristics.

BACKGROUND: Systemic cancer therapies may induce infusion reactions (IRs) or hypersensitivities. Metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapies, including cetuximab and panitumumab, may be subject to these reactions. We conducted a meta-analysis to estimate the IR incidence in this population and identify variations in this incidence by patient or study characteristics. METHODS: A systematic review was conducted to identify observational studies or clinical trials of mCRC patients treated with anti-EGFR therapies that reported occurrences of IRs, hypersensitivity, or allergy/anaphylaxis. The objective of the study was to estimate the incidence of IRs. Random effects models were used to meta-analyze the incidence of IRs overall and stratified by therapy type, study design, geographic location, RAS or KRAS mutation status, grade of reaction severity, and terminology used to describe the reaction. RESULTS: The pooled estimate for IR incidence was 4.9% (95% confidence interval: 3.6%-6.5%). Lower-grade reactions were more common than higher-grade reactions overall and the incidence of reactions among cetuximab patients was nearly four times that of panitumumab patients (6.1% vs 1.6%). CONCLUSIONS: IRs occur in approximately 5% of mCRC patients treated with anti-EGFR therapies, and the incidence varies significantly by grade of severity and therapy type. Studies evaluating these outcomes should consider investigating survival outcomes by IR status to determine its prognostic relevance.

A National Survey of Medical Oncologist's Opinions and Perceptions for Managing Rash Among mCRC Patients Treated with Panitumumab.

INTRODUCTION: This study aimed to describe medical oncologist's opinions and perceptions regarding the management of dermatologic toxicities among metastatic colorectal cancer (mCRC) patients who were treated with panitumumab in the USA and assess if there were differences across demographic and clinical characteristics. METHODS: We developed a survey based on the current literature and expert opinions regarding the management of dermatologic toxicities. The survey was implemented online in September 2016. Eligible oncologists were board certified and had treated at least five new or continuing patients with mCRC in the last 3 months, among whom at least three patients had received or were currently receiving panitumumab. RESULTS: A total of 250 oncologists completed the survey. The data suggest that approximately 82% of patients received recommendations for moisturizer, 88% for sunscreen and 67% for ultraviolet (UV)-protective garments prior to or at the time of initiation of panitumumab therapy. There were minor differences in how dermatologic toxicities were managed across specific demographic or clinical groups. The data also suggest that the management associated with panitumumab use among mCRC patients can be greatly improved. CONCLUSIONS: Our results highlight the urgent need for heightened education regarding dermatologic toxicity management among oncologists who treated mCRC patients with panitumumab. Easily implemented strategies, such as moisturizer, sunscreen, and UV-protective garments should be recommended to all patients. FUNDING: Amgen, Inc. Plain language summary available for this article.

Dermatologic Toxicities: A Chart Review of Clinical Management Among Patients With Metastatic Colorectal Cancer Treated With Panitumumab.

BACKGROUND: At least 90% of patients with metastatic colorectal cancer (mCRC) who are treated with an anti-EGFR will develop a dermatologic toxicity. Preemptive management strategies have been shown to reduce the severity of rash. OBJECTIVES: This article aims to describe treatment modalities used for the management of dermatologic toxicity among patients with mCRC who were treated with panitumumab and to assess the proportion of patients who were recommended preemptive versus reactive management strategies. METHODS: This retrospective chart review evaluated different treatment modalities and routes of administration. The modalities were categorized as prescription or over-the-counter. The timing in relation to the first dose of panitumumab was used to define preemptive versus reactive treatments. FINDINGS: In a sample of 330 patients, only 10% of patients were recommended to begin treatment for rash preemptively. The two most common treatment modalities for preemptively and reactively treated patients were prescription oral antibiotics and prescription topical antibiotics.

Inactivation of Prions and Amyloid Seeds with Hypochlorous Acid.

Hypochlorous acid (HOCl) is produced naturally by neutrophils and other cells to kill conventional microbes in vivo. Synthetic preparations containing HOCl can also be effective as microbial disinfectants. Here we have tested whether HOCl can also inactivate prions and other self-propagating protein amyloid seeds. Prions are deadly pathogens that are notoriously difficult to inactivate, and standard microbial disinfection protocols are often inadequate. Recommended treatments for prion decontamination include strongly basic (pH ≥~12) sodium hypochlorite bleach, ≥1 N sodium hydroxide, and/or prolonged autoclaving. These treatments are damaging and/or unsuitable for many clinical, agricultural and environmental applications. We have tested the anti-prion activity of a weakly acidic aqueous formulation of HOCl (BrioHOCl) that poses no apparent hazard to either users or many surfaces. For example, BrioHOCl can be applied directly to skin and mucous membranes and has been aerosolized to treat entire rooms without apparent deleterious effects. Here, we demonstrate that immersion in BrioHOCl can inactivate not only a range of target microbes, including spores of Bacillus subtilis, but also prions in tissue suspensions and on stainless steel. Real-time quaking-induced conversion (RT-QuIC) assays showed that BrioHOCl treatments eliminated all detectable prion seeding activity of human Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, cervine chronic wasting disease, sheep scrapie and hamster scrapie; these findings indicated reductions of ≥103- to 106-fold. Transgenic mouse bioassays showed that all detectable hamster-adapted scrapie infectivity in brain homogenates or on steel wires was eliminated, representing reductions of ≥~105.75-fold and >104-fold, respectively. Inactivation of RT-QuIC seeding activity correlated with free chlorine concentration and higher order aggregation or destruction of proteins generally, including prion protein. BrioHOCl treatments had similar effects on amyloids composed of human α-synuclein and a fragment of human tau. These results indicate that HOCl can block the self-propagating activity of prions and other amyloids.

Water filter provision and home-based filter reinforcement reduce diarrhea in Kenyan HIV-infected adults and their household members.

Among human immunodeficiency virus (HIV)-infected adults and children in Africa, diarrheal disease remains a major cause of morbidity and mortality. We evaluated the effectiveness of provision and home-based reinforcement of a point-of-use water filtration device to reduce diarrhea among 361 HIV-infected adults in western Kenya by comparing prevalence of self-reported diarrhea before and after these interventions. After provision of the filter, 8.7% of participants reported diarrhea compared with 17.2% in the 3 months before filter provision (odds ratio [OR] = 0.39, 95% confidence interval [95% CI] = 0.23-0.66, P < 0.001). The association was similar among 231 participants who were already taking daily cotrimoxazole prophylaxis before being given a filter (OR = 0.47, 95% CI = 0.25-0.88, P = 0.019). Educational reinforcement was also associated with a modest reduction in self-reported diarrhea (OR = 0.50, 95% CI = 0.20-0.99, P = 0.047). Provision and reinforcement of water filters may confer significant benefit in reducing diarrhea among HIV-infected persons, even when cotrimoxazole prophylaxis is already being used.

The association between malaria and iron status or supplementation in pregnancy: a systematic review and meta-analysis.

INTRODUCTION: Malaria prevention and iron supplementation are associated with improved maternal and infant outcomes. However, evidence from studies in children suggests iron may adversely modify the risk of malaria. We reviewed the evidence in pregnancy of the association between malaria and markers of iron status, iron supplementation or parenteral treatment. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, and the Malaria in Pregnancy library to identify studies that investigated the association between iron status, iron treatment or supplementation during pregnancy and malaria. Thirty one studies contributed to the analysis; 3 experimental and 28 observational studies. Iron supplementation was not associated with an increased risk of P. falciparum malaria during pregnancy or delivery in Africa (summary Relative Risk = 0.89, 95% Confidence Interval (CI) 0.66-1.20, I(2) = 78.8%, 5 studies). One study in Asia reported an increased risk of P. vivax within 30 days of iron supplementation (e.g. adjusted Hazard Ratio = 1.75, 95% CI 1.14-2.70 for 1-15 days), but not after 60 days. Iron deficiency (based on ferritin and C-reactive protein) was associated with lower odds for malaria infection (summary Odds Ratio = 0.35, 0.24-0.51, I(2) = 59.2%, 5 studies). With the exception of the acute phase protein ferritin, biomarkers of iron deficiency were generally not associated with malaria infection. CONCLUSIONS: Iron supplementation was associated with a temporal increase in P vivax, but not with an increased risk of P. falciparum; however, data are insufficient to rule out the potential for an increased risk of P. falciparum. Iron deficiency was associated with a decreased malaria risk in pregnancy only when measured with ferritin. Until there is more evidence, it is prudent to provide iron in combination with malaria prevention during pregnancy.

Impact of helminth diagnostic test performance on estimation of risk factors and outcomes in HIV-positive adults.

BACKGROUND: Traditional methods using microscopy for the detection of helminth infections have limited sensitivity. Polymerase chain reaction (PCR) assays enhance detection of helminths, particularly low burden infections. However, differences in test performance may modify the ability to detect associations between helminth infection, risk factors, and sequelae. We compared these associations using microscopy and PCR. METHODS: This cross-sectional study was nested within a randomized clinical trial conducted at 3 sites in Kenya. We performed microscopy and real-time multiplex PCR for the stool detection and quantification of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, Strongyloides stercoralis, and Schistosoma species. We utilized regression to evaluate associations between potential risk factors or outcomes and infection as detected by either method. RESULTS: Of 153 HIV-positive adults surveyed, 55(36.0%) and 20(13.1%) were positive for one or more helminth species by PCR and microscopy, respectively (p<0.001). PCR-detected infections were associated with farming (Prevalence Ratio 1.57, 95% CI: 1.02, 2.40), communal water source (PR 3.80, 95% CI: 1.01, 14.27), and no primary education (PR 1.54, 95% CI: 1.14, 2.33), whereas microscopy-detected infections were not associated with any risk factors under investigation. Microscopy-detected infections were associated with significantly lower hematocrit and hemoglobin (means of -3.56% and -0.77 g/dl) and a 48% higher risk of anemia (PR 1.48, 95% CI: 1.17, 1.88) compared to uninfected. Such associations were absent for PCR-detected infections unless infection intensity was considered, Infections diagnosed with either method were associated with increased risk of eosinophilia (PCR PR 2.42, 95% CI: 1.02, 5.76; microscopy PR 2.92, 95% CI: 1.29, 6.60). CONCLUSION: Newer diagnostic methods, including PCR, improve the detection of helminth infections. This heightened sensitivity may improve the identification of risk factors for infection while reducing ability to discriminate infections associated with adverse clinical outcomes. Quantitative assays can be used to differentiate infection loads and discriminate infections associated with sequelae.

Evaluation of impact of long-lasting insecticide-treated bed nets and point-of-use water filters on HIV-1 disease progression in Kenya.

OBJECTIVES: Among HIV-1-infected individuals in Africa, coinfection with malaria and diarrhoeal disease may be associated with more rapid HIV-1 disease progression. We sought to determine whether the use of long-lasting insecticide-treated bed nets and simple point-of-use water filters can delay HIV-1 disease progression. DESIGN: A prospective cohort study. SETTING: Two HIV care sites in Kenya. PARTICIPANTS: HIV-1-infected adults not yet meeting criteria for antiretroviral therapy. INTERVENTIONS: One group received the standard of care, whereas the other received long-lasting insecticide-treated bed nets and water filters. Individuals were followed for up to 24 months. MAIN OUTCOME MEASURES: The primary outcome measures were time to CD4 cell count less than 350 cells/µl and a composite endpoint of time to CD4 cell count less than 350 cells/µl and nontraumatic death. Time to disease progression was compared using Cox proportional hazards regression. RESULTS: Of 589 individuals included, 361 received the intervention and 228 served as controls. Median baseline CD4 cell counts were similar (P=0.36). After controlling for baseline CD4 cell count, individuals receiving the intervention were 27% less likely to reach the endpoint of a CD4 cell count less than 350 cells/µl (hazard ratio 0.73; 95% confidence interval 0.57-0.95). CD4 cell count decline was also significantly less in the intervention group (-54 vs. -70 cells/µl per year, P=0.03). In addition, the incidence of malaria and diarrhoea were significantly lower in the intervention group. CONCLUSION: Provision of a long-lasting insecticide-treated bed net and water filter was associated with a delay in CD4 cell count decline and may be a simple, practical and cost-effective strategy to delay HIV-1 progression in many resource-limited settings.

Empiric deworming to delay HIV disease progression in adults with HIV who are ineligible for initiation of antiretroviral treatment (the HEAT study): a multi-site, randomised trial.

BACKGROUND: Co-infection with HIV and helminths is common in sub-Saharan Africa and findings from previous studies have suggested that anthelmintic treatment might delay immunosuppression in people with HIV. We aimed to assess the efficacy of empiric deworming of adults with HIV in delaying HIV disease progression. METHODS: In this non-blinded randomised trial, we enrolled adults (aged ≥18 years) with HIV who did not meet criteria for the initiation of antiretroviral treatment from three sites in Kenya. Using a computer-generated sequence, we randomly assigned (1:1) eligible participants to either empiric albendazole every 3 months plus praziquantel annually (treatment group) or to standard care (control group). Participants were followed up for 24 months. We measured CD4 cell counts every 6 months and plasma HIV RNA annually. The primary endpoints were a CD4 count of less than 350 cells per µL and a composite endpoint consisting of the first occurrence of a CD4 count of less than 350 cells per µL, first reported use of antiretroviral treatment, and non-traumatic deaths. We compared these measures by use of Cox proportional hazards regression and Kaplan-Meier survival analyses. Primary analysis was done by intention to treat. The trial was registered with ClinicalTrials.gov, number NCT0050722. FINDINGS: Between Feb 6, 2008, and June 21, 2011, we enrolled and followed-up 948 participants; 469 were allocated to the treatment group and 479 to the control group. All participants were provided with co-trimoxazole prophylaxis. Median baseline CD4 cell counts and HIV RNA concentrations did not differ between groups. We recorded no statistically significant difference between the treatment and control groups in the number of people reaching a CD4 count of fewer than 350 cells per µL (41·6 events per 100 person-years vs 46·2 events per 100 person-years; hazard ratio 0·89, 95% CI 0·75-1·06, p=0·2) or the composite endpoint (44·0 events per 100 person-years vs 49·8 events per 100 person-years; 0·88, 0·74-1·04, p=0·1). Serious adverse events, none of which thought to be treatment-related, occurred at a similar frequency in both groups. INTERPRETATION: Our findings do not suggest an effect of empiric deworming in the delaying of HIV disease progression in adults with HIV in an area where helminth infection is common. Alternative approaches are needed to delay HIV disease progression in areas where co-infections are common.

Determinants of use of insecticide treated nets for the prevention of malaria in pregnancy: Jinja, Uganda.

BACKGROUND: One established means of preventing the adverse consequences of malaria during pregnancy is sleeping under an insecticide treated net (ITN) throughout pregnancy. Despite increased access to this intervention over time, consistent ITN use during pregnancy remains relatively uncommon in sub-Saharan Africa. METHODOLOGY/PRINCIPAL FINDINGS: We sought to identify determinants of ITN use during pregnancy. Utilizing a population-based random sample, we interviewed 500 women living in Jinja, Uganda, who had been pregnant in the past year. ITN ownership at the start of pregnancy was reported by 359 women (72%) and 28 women (20%) acquired an ITN after the first trimester of pregnancy. Among 387 ITN owners, 73% reported either always sleeping under the ITN during all trimesters of pregnancy, or after acquiring their net. Owning more than 1 net was slightly associated with always sleeping under an ITN during pregnancy (RR: 1.13; 95% CI: 1.00, 1.28). Women who always slept under an ITN during pregnancy were more likely to be influenced by an advertisement on the radio/poster than being given an ITN free of charge (RR: 1.48; 95% CI: 1.24, 1.76). No differences were found between other socio-demographic factors, pregnancy history, ANC use or socio-cultural factors. CONCLUSIONS/SIGNIFICANCE: While self-reported ITN ownership and use was common throughout pregnancy, we were unable to pinpoint why a sizable fraction of Ugandan women did not always adhere to recommendations for use of an ITN during pregnancy. More data are needed on the capacity of individual households to support the installation of ITNs which may provide insight into interventions targeted at improving the convenience and adherence of daily ITN use.

Health care workers' ability and willingness to report to work during public health emergencies.

OBJECTIVES: We conducted a county-wide survey to assess the ability and willingness of health care workers to report to work during a pandemic influenza and a severe earthquake and to identify barriers and strategies that would help them report to work. METHODS: A stratified random sample of 9211 health care workers was selected from the Washington state licensure database and from health care agencies. We assessed correlates between self-reported ability and willingness to report to work and demographic and employer-related variables under two scenarios, influenza pandemic and a severe earthquake. RESULTS: For the influenza pandemic scenario, 95% of respondents reported that they would be able and 89% reported that they would be willing to report to their usual place of work. Seventy-four percent of respondents reported that they would be able and 88% would be willing to report to their usual place of work following a severe earthquake. The most frequently cited strategies that would help respondents report to work during an influenza pandemic were the availability of anti-viral influenza treatment and the ability to work from home. For persons with children at home, the strategy to increase ability to report to work during an earthquake was the availability of child care. CONCLUSIONS: The majority of the King County health care workforce is willing and able to respond to an influenza pandemic or a severe earthquake.

Species-specific treatment effects of helminth/HIV-1 co-infection: a systematic review and meta-analysis.

In sub-Saharan Africa, over 22 million people are estimated to be co-infected with both helminths and HIV-1. Several studies have suggested that de-worming individuals with HIV-1 may delay HIV-1 disease progression, and that the benefit of de-worming may vary by individual helminth species. We conducted a systematic review and meta-analysis of the published literature to determine the effect of treatment of individual helminth infections on markers of HIV-1 progression (CD4 count and HIV viral load). There was a trend towards an association between treatment for Schistosoma mansoni and a decrease in HIV viral load (Weighted mean difference (WMD)=-0·10; 95% Confidence interval (CI): -0·24, 0·03), although this association was not seen for Ascaris lumbricoides, hookworm or Trichuris trichiura. Treatment of A. lumbricoides, S. mansoni, hookworm or T. trichiura was not associated with a change in CD4 count. While pooled data from randomized trials suggested clinical benefit of de-worming for individual helminth species, these effects decreased when observational data were included in the pooled analysis. While further trials are needed to confirm the role of anthelmintic treatment in HIV-1 co-infected individuals, providing anthelmintics to individuals with HIV-1 may be a safe, inexpensive and practical intervention to slow progression of HIV-1.