Order Substitutions and Education for Balanced Crystalloid Solution Use in an Integrated Health Care System and Association With Major Adverse Kidney Events.

Importance: Trials comparing balanced crystalloids with normal saline have yielded mixed results regarding reductions in kidney complications and mortality for hospitalized patients receiving intravenous fluids. Objective: To evaluate the association of a multifaceted implementation program encouraging the preferential use of lactated Ringer solution with patient outcomes and intravenous fluid-prescribing practices in a large, multilevel health care system. Design, Setting, and Participants: This type 2 hybrid implementation and comparative effectiveness study enrolled all patients 18 years or older who received 1 L or more of intravenous fluids while admitted to an emergency department and/or inpatient unit at 1 of 22 hospitals in Idaho and Utah between November 1, 2018, and February 29, 2020. An interrupted time series analysis was used to assess study outcomes before and after interventions to encourage use of lactated Ringer solution. Exposures: Implementation program combining order set modification, electronic order entry alerts, and sequential clinician-targeted education to encourage prescribing of lactated Ringer solution instead of normal saline. Main Outcomes and Measures: The primary implementation outcome was the patient-level proportion of intravenous fluids that was balanced crystalloids. The primary effectiveness outcome was the incidence of major adverse kidney events (MAKE30)-a composite of new persistent kidney dysfunction, new initiation of dialysis, and death-at 30 days. Results: Among 148 423 patients (median [IQR] age, 47 [30-67] years; 91 302 women [61%]), the proportion of total fluids received that was lactated Ringer solution increased from 28% to 75% in the first week vs the last week of the study (immediate implementation effect odds ratio [OR], 3.44; 95% CI, 2.79-4.24). The estimated MAKE30 absolute risk reduction was 2.2% (95% CI, 1.3%-3.3%) based on interrupted time series analysis showing a decrease in the week-on-week trend for MAKE30 (OR difference, 0.03; 95% CI, 0.03-0.03, P < .001). The immediate postimplementation OR for MAKE30 was 0.88 (95% CI, 0.76-1.01), with a decrease in persistent kidney dysfunction (OR, 0.80; 95% CI, 0.69-0.93) and mortality (OR, 0.78; 95% CI, 0.65-0.93) but not dialysis (OR, 1.00; 95% CI, 0.76-1.32). Conclusions and Relevance: In this comparative effectiveness study, an implementation program was associated with an increase in the proportion of fluids administered as lactated Ringer solution compared with normal saline and was associated with a reduction in MAKE30 events among patients treated in a large integrated health care system.

Blood donors in Kenya: a comparison of voluntary and family replacement donors based on a population-based survey.

BACKGROUND AND OBJECTIVES: Blood safety and sufficiency are major challenges in Kenya and other sub-Saharan African countries forcing many countries to rely on family replacement donors (FRD). We analysed data from a national AIDS indicator survey to describe blood donors in Kenya and potential risks of transfusion transmissible infections (TTI) comparing voluntary donors and FRD. MATERIALS AND METHODS: A population-based, cross-sectional survey was conducted in 2007 among 15- to 64-year-olds. Consenting participants were interviewed about blood donation history and were tested for HIV, HSV-2 and syphilis. RESULTS: Of the 17,940 people surveyed, 445 (2·3%) reported donating blood in the prior 12 months. Sixty-four per cent were voluntary donors, and the rest were FRD. Compared to FRD, the majority of voluntary donors were <25 years old (59% versus 18%), from the highest wealth quintile (57% versus 42%) and single (64% versus 23%). In addition, voluntary donors were less likely to have been sexually active than replacement donors (43% versus 13%). HIV prevalence was lower among voluntary donors than among FRD (2·6% versus 7·4%, P-value=0·07). CONCLUSIONS: The majority of blood donors in Kenya are voluntary with lower potential risk of TTI.

Developing WHO guidelines with pragmatic, structured, evidence-based processes: A case study.

Many guidelines, including those produced by the World Health Organisation (WHO), have failed to adhere to rigorous methodological standards. Operational examples of guideline development processes may provide important lessons learned to improve the rigour and quality of future guidelines. To this end, this paper describes the process of developing WHO guidelines on prevention and care interventions for adults and adolescents living with HIV. Using a pragmatic, structured, evidence-based approach, we created an organising committee, identified topics, conducted systematic reviews, identified experts and distributed evidence summaries. Subsequently, 55 global HIV experts drafted and anonymously submitted guideline statements at the beginning of a conference. During the conference, participants voted on statements using scales evaluating appropriateness of the statements, strength of recommendation and level of evidence. After review of voting results, open discussion, re-voting and refinement of statements, a draft version of the guidelines was completed. A post-conference writing team refined the guidelines based on pre-determined guideline writing principles and incorporated external comments into a final document. Successes and challenges of the guideline development process were identified and are used to highlight current issues and debates in developing guidelines with a focus on implications for future guideline development at WHO.

A simple screening tool for active tuberculosis in HIV-infected adults receiving antiretroviral treatment in Uganda.

SETTING: Reliable clinical algorithms that screen for active tuberculosis (TB) in human immunodeficiency virus (HIV) infected people initiating or receiving antiretroviral treatment (ART) in sub-Saharan Africa could reduce the need for diagnostic procedures. METHODS: We estimated the utility of six TB-related signs and symptoms, alone or in combination, compared with the Uganda Ministry of Health diagnostic guidelines for participants with prevalent (baseline), early ART (< or = 3 months on ART) and incident TB (>3 months on ART). RESULTS: Of 1995 participants screened for ART eligibility, 71 (3.6%) had prevalent TB. The presence of any one of the following: cough > or = 3 weeks, fever > or = 4 weeks, lymphadenopathy or baseline body mass index < or = 18 kg/m(2) had a sensitivity of 99% (95%CI 96-100), a specificity of 66% (95%CI 64-68) and a negative predictive value (NPV) of 100% (95%CI 99-100) for predicting active TB. During ART follow-up, TB incidence was 2.4 (95%CI 1.6-3.4)/100 person-years. The presence of cough > or = 3 weeks or general weakness was 100% sensitive (95%CI 99-100), 66% specific (95%CI 59-74) and had an NPV of 100% (95%CI 99-100). CONCLUSION: Use of a simple TB screening algorithm can accurately identify, in a resource-poor African setting, HIV-infected individuals who require further procedures to diagnose active TB.

Cost-utility of tuberculosis prevention among HIV-infected adults in Kampala, Uganda.

SETTING: Treatment of latent tuberculosis (TB) infection using isoniazid preventive therapy (IPT) in a human immunodeficiency virus (HIV) volunteer counseling and testing center in Kampala, Uganda. OBJECTIVE: To analyze the cost-utility of an IPT program for persons newly diagnosed with HIV. DESIGN: The cost-utility analysis of the IPT program was conducted using Markov cohort simulation methods. Newly diagnosed HIV-infected persons were evaluated using tuberculin skin test (TST); those with positive TST were offered IPT for 9 months (targeted testing strategy). An alternative strategy of offering IPT to all HIV-infected clients without TST screening was also evaluated (treat all strategy). The cost-utility of targeted testing was compared to the 'no program' and the 'treat all' strategies. RESULTS: The IPT program with the targeted testing strategy would produce 11 quality-adjusted life-years (QALYs) per 100 HIV-infected clients compared to no program. Offering IPT using the treat all strategy gained an additional 30 QALYs per 100 clients compared to targeted testing. Compared to no program, the incremental cost-utility of the targeted testing program was US$102/QALY gained. The cost-utility of the IPT program under the treat all strategy was US$106/QALY gained compared to the targeted testing strategy. CONCLUSIONS: The provision of IPT for HIV-infected persons was cost-effective. The use of TST screening prior to IPT reduced costs per QALY gained, but saved fewer overall QALYs.

Trends and predictors of quality of life among HIV-infected adults taking highly active antiretroviral therapy in rural Uganda.

We examined trends and predictors of quality of life (QOL) over 12 months among a prospective cohort of 947 HIV-1-infected adults initiating highly active antiretroviral therapy (HAART) between May 2003 and May 2004 in rural Uganda. Participants provided clinical, demographic and psychosocial data at baseline and every three months thereafter. Outcome measures included physical and mental health summary scores based on the Medical Outcomes Study-HIV Health Survey (MOS-HIV). Generalised estimating equations were used to assess magnitude of change in summary scores and factors associated with QOL. Of 710 women and 237 men enrolled, the mean age was 38.7 years and mean baseline CD4 cell count was 124.1 cells/microL. At enrollment, physical and mental health summary scores were 39.2 and 40, respectively. By 12 months of HAART, scores increased by 11.2 points (p <0.001) and 7.4 points (p <0.001), respectively. For both scores, most gains were achieved by the third month of therapy. While several clinical, psychosocial and sociodemographic factors predicted QOL at HAART initiation, financial dependence on others was the only remaining predictor after controlling for time on HAART. Interventions to enhance the economic and employment opportunities of patients taking HAART in rural Africa may help maximise gains in QOL.

Tuberculosis case finding and preventive therapy in an HIV voluntary counseling and testing center in Uganda.

SETTING: A large, urban human immunodeficiency virus (HIV) voluntary counseling and testing (VCT) center in Kampala, Uganda. OBJECTIVE: Tuberculosis (TB) is a leading cause of morbidity and mortality in persons with HIV infection in sub-Saharan Africa. Intensified TB case finding and use of isoniazid preventive therapy (IPT) for latent infection reduces the burden of TB, but few programs have been implemented due to concerns about feasibility. DESIGN: Retrospective evaluation of a TB case finding and IPT program. RESULTS: Over a 25-month period, 6305 patients newly diagnosed with HIV infection underwent evaluation: 293 (5%) had TB disease; 1955 (37%) patients were not eligible for preventive therapy because they lived > 20 km away, had advanced HIV disease, or had previously had TB. Of 3366 who had a tuberculin skin test (TST) placed, 2548 (76%) had the TST read; 894 (35%) of these were positive. Of 506 persons who started treatment, 335 (66%) completed it. CONCLUSION: This unique program was feasible, detected a high proportion of undiagnosed TB, and successfully treated persons with latent infection. Expanding access to HIV VCT as well as collaboration between HIV/ AIDS and TB programs can increase the proportion of HIV-infected persons who can benefit from these programs.

Cost-effectiveness of including tuberculin skin testing in an IPT program for HIV-infected persons in Uganda.

SETTING: Tuberculosis (TB) is the most common opportunistic infection among persons with human immunodeficiency virus or the acquired immune-deficiency syndrome (HIV/AIDS). Isoniazid preventive therapy (IPT) effectively treats latent TB infection (LTBI) and prevents progression to active TB. OBJECTIVE: To analyse the costs and cost-effectiveness of tuberculin skin testing (TST) prior to offering IPT. DESIGN: We implemented a program for LTBI screening and IPT using TST for persons with HIV at a voluntary counseling and testing (VCT) center in Kampala, Uganda. Cost-effectiveness analyses using Markov methods were adopted to compare strategies of using and not using TST before offering IPT. RESULTS: The program enrolled 7073 persons with HIV. Based on the prevalence of LTBI in the population, 34/100 HIV-infected patients would benefit from IPT. The results showed that 28% of LTBI patients would be treated using the TST strategy, and 40% would be treated with a non-TST strategy. Compared to no intervention, the estimated incremental cost of identifying and providing IPT using TST was dollars 211 per patient; the incremental cost using a non-TST strategy was dollars 768 per patient. CONCLUSION: At a large VCT center in Uganda, the inclusion of TST to identify the HIV-infected persons who will most benefit from IPT is cost-effective.

Chronic herpes simplex virus type-2 infection and HIV viral load.

By December 2003, the estimated adult HIV/AIDS prevalence rate in sub-Saharan Africa was 7.5-8.5%, and rates of herpes simplex virus type-2 (HSV-2) infection among adults aged >30 years ranged from 60% to 82%. However, little is known about the natural history of HIV/HSV-2 co-infection in this population. We evaluated HIV viral load and CD4+ cell counts among persons with and without chronic HSV-2 co-infection in a cross-sectional study of HIV-infected persons not receiving antiretroviral therapy. HSV-2 and HIV co-infection was associated with a 0.3 log copies/mL higher HIV viral load compared with persons without HSV-2 infection (P=0.014). Chronic HSV-2 infection may have a negative effect on the clinical course of persons with HIV.

Living with discordance: knowledge, challenges, and prevention strategies of HIV-discordant couples in Uganda.

Prevalence of HIV-discordance among couples in sub-Saharan Africa is high. Negative partners are at high risk of HIV infection but few HIV/AIDS service providers have developed effective counseling messages for HIV-discordant couples. To identify clients' explanations for discordance, challenges, and prevention strategies, 24 in-depth interviews and 4 focus group discussions were conducted with 32 female and 35 male members of HIV-discordant couples who sought HIV voluntary counseling and testing (VCT) in Uganda. In addition, counselor explanations for discordance were gathered from 62 counselor trainers during 3 interactive workshops. Misconceptions about discordance were widespread among clients and counselors. Common explanations included: the concept of a hidden infection not detectable by HIV tests, belief in immunity, the thought that gentle sex protected HIV-negative partners, and belief in protection by God. Such explanations for discordance reinforced denial of HIV risk for the negative partner within discordant couples and potentially increased transmission risk. Couples identified negotiation of sexual relations as their most formidable challenge. Prevention strategies included condom use, abstinence and separation of beds, contractual agreements for outside sexual partners, and relationship cessation. Discordant couples represent a critical risk group and improved counseling protocols that clearly explain discordance, emphasize high risk of transmission, and support risk reduction are urgently needed.

Leaving sex work: barriers, facilitating factors and consequences for female sex workers in northern Thailand.

Factors facilitating or inhibiting women's ability to leave sex work are still poorly characterized, and little is known about women's lives after they leave the profession. This paper presents findings from a qualitative study about factors affecting women's ability to leave sex work and influencing their lives after leaving. We interviewed 42 current and former female sex workers (FSWs) drawn from a cohort study of 500 FSWs in northern Thailand. All but one of the participants had quit sex work at least once. The majority experienced one or more quit-re-entry-quit cycles. Women's ability and decisions to leave sex work were determined primarily by four factors: economic situation, relationship with a steady partner, attitudes towards sex work and HIV/AIDS experience. Economic concerns, ranging from survival needs to materialistic desires, had the strongest influence. Most women perceived their risk for HIV infection to be lower after leaving sex work, but three of the 17 HIV-infected women acquired infection after having left, presumably from their steady partners. Prevention efforts should guide women as they transition out of commercial sex work. Interventions aimed at assisting women wanting to leave sex work need to address the role of economic factors.

High prevalence and incidence of sexually transmitted diseases in urban adolescent females despite moderate risk behaviors.

To better understand the prevalence, incidence, and risk factors for sexually transmitted diseases (STDs) among female adolescents, a prospective 6-month cohort study was conducted at four teen clinics in a southeastern city. At enrollment, 260 (40%) of 650 sexually active females ages 14-19 years had an STD: chlamydia, 27%; herpes simplex virus type 2 (HSV-2), 14%; gonorrhea, 6%; trichomoniasis, 3%; and hepatitis B, 2%. At follow-up, 112 (23%) of 501 participants had an incident infection: chlamydia, 18%; HSV-2, 4%; gonorrhea, 4%; and trichomoniasis, 3%. At either enrollment or follow-up, 53% had >/=1 STD; of those with 1 lifetime partner, 30% had an STD. Having a new partner (odds ratio [OR], 2.2; 95% confidence interval [CI], 1. 1-4.2) or friends who sell cocaine (OR, 1.6; CI, 1.0-2.6) was independently associated with incident infection. STD incidence and prevalence were extremely high in this population, even in teenagers with only 1 lifetime partner. Individual risk behaviors appeared less important for STD risk than population factors.

HIV-1 seroprevalence among childbearing women in northern Thailand: monitoring a rapidly evolving epidemic.

OBJECTIVES: To describe trends in prevalence of HIV-1 infection among women giving birth at Chiang Rai Hospital (CRH) and to assess risk factors associated with HIV infection in this population. DESIGN: Analysis of hospital registry data for all deliveries at CRH from 1990 to mid-1997. METHODS: From 1990 to mid-1997, women giving birth at CRH were tested for HIV-1 infection using enzyme immunoassay (EIA); positive sera were confirmed using a different manufacturer's EIA. Demographic and clinical data were abstracted from delivery-ward log books. RESULTS: Data from 40723 deliveries indicated that overall HIV-1 seroprevalence increased sharply, from 1.3% in 1990 to a peak of 6.4% in 1994, and then declined to 4.6% in the first 6 months of 1997. Prevalence was highest, at 7.0%, among young (age < or = 24 years) primigravidas, compared with 2.4% among older (age > or = 25 years) multigravidas. When we controlled for age, prevalence declined 40% from 1994 to 1997 among young primigravidas (95% confidence interval for percentage reduction, 16-57). Amongst older multigravid women, prevalence was consistently lower but increased steadily from 2.7% in 1994 to 3.4% in 1997. CONCLUSIONS: A rapid rise in HIV prevalence in childbearing women was followed by a sharp decline among young primigravidas. In each year, the prevalence was highest among young primigravidas. They may be the best subgroup of pregnant women for monitoring HIV epidemic trends, but they also represent a challenging prevention priority that will require its own targeted interventions.

Using computer simulated results of a bulk drug substance assay to determine acceptance criteria for method validation.

PURPOSE: To determine the statistical variability expected for a well designed HPLC assay of a bulk drug substance (BDS). The results are used to develop appropriate acceptance criteria for a method validation protocol as well as to evaluate the level of uncertainty expected for assay results using a variety of sampling/injection schemes. METHODS: Computer simulation was used to generate a large quantity of data and the variability of the mock results was evaluated. Error propagation was also calculated, whenever possible, to confirm results obtained from the simulations. RESULTS: Protocol acceptance criteria were developed that were consistent with the expected variability for data resulting from the execution of the validation protocol. In certain cases simulations provided the only avenue of obtaining results that could not otherwise be readily determined. CONCLUSIONS: Computer modeling can be used to obtain suitable acceptance criteria for validation results which are consistent with method variability. This is particularly significant in the case of linearity where it has been difficult to develop acceptance criteria based on anything other than analyst intuition and experience. Assay simulations clearly demonstrated that the variability expected for a typical BDS assay is large relative to the average specification range and therefore little insight about relative purity can be gained comparing individual passing assay results.

Involving communities through feedback on evaluation.

PIP: In Uganda, the AIDS Support Organization (TASO) operating principle is community involvement in initiating and defining its own responses to the AIDS crisis. The community established objectives and strategies and selects TASO workers. In the communities of Muswangali (1500 people), Bbira (300 people), Biharwe (2500 people), and Nyeihanga (2500 people), TASO decided that community remobilization was needed. The idea was to involve the communities in the evaluation process. Training sessions were conducted in 1990 and 1991 among community leaders. The outcome were conducted in evaluation, the introduction of KAP surveys, and the initiation of Evaluation Presentation Feedback (EPF) sessions, which would inform the community on pertinent issues. The following topics were selected: self-reported numbers of sexual partners, personal risk perceptions, knowledge on the asymptomatic phase of HIV infections, and prevention strategies suitable to the community. THese topics and survey results were discussed with community members from a variety of age groups in half day workshops. There was a range of numbers of participants in each of the four community workshops, from 50 in Bbira to 500 in Muswangali. TASO trainers familiar with the communities conducted the sessions. EPF sessions used different methods of translating survey results. One way of showing how perceptions may be different from knowledge was to first ask the audience how many partners men had currently had on the average and then to supply the figures from the KAP survey. In one example, the community guessed 2.5 partners, but the actual figures were 1.2 partners. In another session, community partners were asked to interpret and discuss the data and its meaning. The aim of the EPF was to review the survey results and establish new objectives for AIDS programming. For example, in Biharwe and Nyeihanga, there was a need for identified increased condom distribution. The mobilization of these communities was accomplished due to these workshop sessions. Other mechanisms for developing culturally sensitive and appropriate feedback from the community are needed.^ieng

Effect of feeding polyunsaturated fatty acids with a low vitamin E diet on blood levels of tocopherol in men performing hard physical labor.

A diet made low in vitamin E by elimination of foods considered good sources of the vitamin was fed for 13 months to two groups of men engaged in strenuous labor. With a daily average dietary intake of about 9.4 mg of total tocopherols, a progressive decline in blood levels of tocopherol from 1.42 to 0.81 mg/100 ml was observed in the five control subjects. The test group of 30 men received a daily supplement of tocopherol-stripped safflower oil containing 88 g of polyunsaturated fatty acids and 2.3 mg of tocopherols. Average blood plasma levels of tocopherol in this group dropped rapidly from an initial value of 1.01 to about 0.5 mg/100 ml within 5 months and remained relatively stable thereafter. No muscular weakness or other physical symptoms were reported.