EQ-5D-5L and SF-6D health utility index scores in patients with myasthenia gravis.

BACKGROUND AND PURPOSE: Health utilities are a preference-based method of valuing health states that are used in healthcare research, such as economic evaluations. There are limited health utility valuation data for patients with myasthenia gravis (MG). The aim of the study was to describe health utilities for patients with MG and different health states, using the EQ-5D-5L and SF-6D utility instruments, and to explore clinical and demographic determinants of utilities in this population. METHODS: Patients completed the EQ-5D-5L and SF-6D. In addition, patients were assessed with the Myasthenia Gravis Foundation of America classification, Myasthenia Gravis Impairment Index and MG-QOL15 as disease-specific measures, and the Neuro-QoL Fatigue scale. We calculated mean utilities for each Myasthenia Gravis Foundation of America severity class. We built regression models for the EQ-5D-5L and SF-6D to determine the clinical and demographic factors that determine patients' valuation of their health state. RESULTS: Among 254 patients, mean EQ-5D-5L health utilities were as follows: Remission, 0.94 ± 0.03; Minimal Manifestations, 0.92 ± 0.04; Class I, 0.89 ± 0.06; Class II, 0.78 ± 0.16; Class III, 0.58 ± 0.24 and Class IV, 0.61 ± 0.22. Mean SF-6D health utilities were as follows: Remission, 0.83 ± 0.07; Minimal Manifestations, 0.86 ± 0.14; Class I, 0.82 ± 0.14; Class II, 0.67 ± 0.12; Class III, 0.56 ± 0.11 and Class IV, 0.50 ± 0.10. The limb/axial scores were more highly correlated to health utilities than ocular or bulbar scores. CONCLUSIONS: We present estimates of health utilities for patients with MG that can be used in cost-utility and decision analyses. Limb/axial symptoms had a higher impact on health utilities than ocular or bulbar symptoms, which might reflect the impact of mobility on health valuation.

Band-like calcification with simplified gyration and polymicrogyria: report of 10 new families and identification of five novel OCLN mutations.

Band-like calcification with simplified gyration and polymicrogyria (BLC-PMG) is an extremely rare autosomal recessive disorder with distinctive clinical and neuroimaging findings. To date, only 17 patients from 9 unrelated families with BLC-PMG have been reported worldwide. Herein, we describe a series of 13 new patients derived from 10 unrelated Egyptian families. Patients presented at early life with the classic phenotype including severe microcephaly, failure to acquire developmental skills, growth failure and the distinguished calcification patterns involving the cortex, thalami, basal ganglia and pons. Additional features not reported before included calcification of the cerebellum (eight patients: 61.5%) and imperforate anus and undescended testis in a single patient. Molecular studies of the OCLN gene (NM_001205254) identified six distinct candidate mutations. Interestingly, the deletion mutation of the transmembrane domain in exons 3 and 4 (c.51-?_730-?del, p.Lys18_Glu243) was found in five unrelated families (50%), suggesting a founder mutation in our population. On the other hand, five novel truncating mutations (c.809delA (p.K270Rfs*62), c.858_861delTTAT (p.I286Mfs*45), c.1037+5G>C, c.1169C>G (p.S390*) and c.1180delG (p.E394Sfs*91)) were detected, each in one family. To our knowledge, this is the largest series of patients with BLC-PMG. Cerebellum calcification is an additional relevant finding in our series, thus expanding the neuroradiological phenotype of this syndrome.

Factors influencing initial implementation of an online community-based exercise intervention with adults living with HIV: a systems approach.

Introduction: Online community-based exercise (CBE) is a digital health intervention and rehabilitation strategy that promotes health among people living with HIV. Our aim was to describe the factors influencing initial implementation of a pilot online CBE intervention with adults living with HIV using a systems approach, as recommended by implementation science specialists. Methods: We piloted the implementation of a 6-month online CBE intervention and 6-month independent exercise follow up, in partnership with the YMCA in Toronto, Canada. We recruited adults living with HIV who identified themselves as safe to engage in exercise. The intervention phase included personalized exercise sessions online with a personal trainer; exercise equipment; access to online exercise classes; and a wireless physical activity monitor. Two researchers documented implementation factors articulated by participants and the implementation team during early implementation, defined as recruitment, screening, equipment distribution, technology orientation, and baseline assessments. Data sources included communication with participants; daily team communication; weekly team discussions; and in-person meetings. We documented implementation factors in meeting minutes, recruitment screening notes, and email communication; and analyzed the data using a qualitative descriptive approach using a systems engineering method called Cognitive Work Analysis. Results: Thirty-three adults living with HIV enrolled in the study (n = 33; median age: 52 years; cis-men: 22, cis-women: 10, non-binary: 1). Fifty-five factors influencing implementation, spanned five layers: (i) Natural, including weather and the COVID-19 virus; (ii) Societal, including COVID-19 impacts (e.g. public transit health risks impacting equipment pick-ups); (iii) Organizational, including information dissemination (e.g. tech support) and logistics (e.g. scheduling); (iv) Personal, including physical setting (e.g. space) and digital setting (e.g. device access); and (v) Human, including health (e.g. episodic illness) and disposition (e.g. motivation). The implementation team experienced heightened needs to respond rapidly; sustain engagement; and provide training and support. Additional organizational factors included a committed fitness training and research team with skills spanning administration and logistics, participant engagement, technology training, physical therapy, and research ethics. Conclusion: Fifty-five factors spanning multiple layers illustrate the complexities of online CBE with adults living with HIV. Initial implementation required a dedicated, rehabilitation-centred, multi-skilled, multi-stakeholder team to address a diverse set of factors.

Vitamin K supplementation for the primary prevention of osteoporotic fractures: is it cost-effective and is future research warranted?

UNLABELLED: Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. It would be a cost-effective intervention at commonly used thresholds, but high uncertainty around the cost-effectiveness estimates persists. Further research on the effect of vitamin K on fractures is warranted. INTRODUCTION: Vitamin K might have a role in the primary prevention of fractures, but uncertainties about its effectiveness and cost-effectiveness persist. METHODS: We developed a state-transition probabilistic microsimulation model to quantify the cost-effectiveness of various interventions to prevent fractures in 50-year-old postmenopausal women without osteoporosis. We compared no supplementation, vitamin D(3) (800 IU/day) with calcium (1,200 mg/day), and vitamin K(2) (45 mg/day) with vitamin D(3) and calcium (at the same doses). An additional analysis explored replacing vitamin K(2) with vitamin K(1) (5 mg/day). RESULTS: Adding vitamin K(2) to vitamin D(3) with calcium reduced the lifetime probability of at least one fracture by 25%, increased discounted survival by 0.7 quality-adjusted life-years (QALYs) (95% credible interval (CrI) 0.2; 1.3) and discounted costs by $8,956, yielding an incremental cost-effectiveness ratio (ICER) of $12,268/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 95% and the population expected value of perfect information (EVPI) was $28.9 billion. Adding vitamin K(1) to vitamin D and calcium reduced the lifetime probability of at least one fracture by 20%, increased discounted survival by 0.4 QALYs (95% CrI -1.9; 1.4) and discounted costs by $4,014, yielding an ICER of $9,557/QALY. At a $50,000/QALY threshold, the probability of cost-effectiveness was 80% while the EVPI was $414.9 billion. The efficacy of vitamin K was the most important parameter in sensitivity analyses. CONCLUSIONS: Lifetime supplementation with vitamin K, vitamin D(3), and calcium is likely to reduce fractures and increase survival in postmenopausal women. Given high uncertainty around the cost-effectiveness estimates, further research on the efficacy of vitamin K on fractures is warranted.

Preferences for surveillance strategies for women treated for high-grade precancerous cervical lesions.

OBJECTIVES: Data are lacking on how women view alternative approaches to surveillance for cervical cancer after treatment of high-grade cervical intraepithelial neoplasia. We measured and compared patient preferences (utilities) for scenarios with varying surveillance strategies and outcomes to inform guidelines and cost-effectiveness analyses of post-treatment surveillance options. METHODS: English- or Spanish-speaking women who had received an abnormal Pap test result within the past 2 years were recruited from general gynecology and colposcopy clinics and newspaper and online advertisements in 2007 and 2008. Participation consisted of one face-to-face interview, during which utilities for 11 different surveillance scenarios and their associated outcomes were elicited using the time tradeoff metric. A sociodemographic questionnaire also was administered. RESULTS: 65 women agreed to participate and successfully completed the preference elicitation exercises. Mean utilities ranged from 0.989 (undergoing only a Pap test, receiving normal results) to 0.666 (invasive cervical cancer treated with radical hysterectomy or radiation and chemotherapy). Undergoing both Pap and HPV tests and receiving normal/negative results had a lower mean utility (0.953) then undergoing only a Pap test and receiving normal results (0.989). Having both tests and receiving normal Pap but positive HPV results was assigned an even lower mean utility (0.909). 15.9% of the respondents gave higher utility scores to the Pap plus HPV testing scenario (with normal/negative results) than to the "Pap test alone" scenario (with normal results), while 17.5% gave the Pap test alone scenario a higher utility score. CONCLUSIONS: Preferences for outcomes ending with normal results but involving alternative surveillance processes differ substantially. The observed differences in utilities have important implications for clinical guidelines and cost-effectiveness analyses.

Cost-effectiveness of voluntary HIV screening in Russia.

Russia has one of the world's fastest growing HIV epidemics, and HIV screening has been widespread. Whether such screening is an effective use of resources is unclear. We used epidemiologic and economic data from Russia to develop a Markov model to estimate costs, quality of life and survival associated with a voluntary HIV screening programme compared with no screening in Russia. We measured discounted lifetime health-care costs and quality-adjusted life years (QALYs) gained. We varied our inputs in sensitivity analysis. Early identification of HIV through screening provided a substantial benefit to persons with HIV, increasing life expectancy by 2.1 years and 1.7 QALYs. At a base-case prevalence of 1.2%, once-per-lifetime screening cost $13,396 per QALY gained, exclusive of benefit from reduced transmission. Cost-effectiveness of screening remained favourable until prevalence dropped below 0.04%. When HIV-transmission-related costs and benefits were included, once-per-lifetime screening cost $6910 per QALY gained and screening every two years cost $27,696 per QALY gained. An important determinant of the cost-effectiveness of screening was effectiveness of counselling about risk reduction. Early identification of HIV infection through screening in Russia is effective and cost-effective in all but the lowest prevalence groups.

A STAT4 variant increases liver fibrosis risk in Caucasian patients with chronic hepatitis B.

BACKGROUND: Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional mechanisms for this effect are unknown and the role of the variant in modulating HBV disease in Caucasians has not been investigated. AIMS: To determine whether STAT4 genetic variation is associated with liver injury in Caucasian patients with CHB and to investigate potential mechanisms mediating this effect. METHODS: STAT4 rs7574865 was genotyped in 1085 subjects (830 with CHB and 255 healthy controls). STAT4 expression in liver, PBMCs and NK cells, STAT4 phosphorylation and secretion of interferon-gamma (IFN-γ) according to STAT4 genetic variation was examined. RESULTS: STAT4 rs7574865 genotype was independently associated with hepatic inflammation (OR: 1.42, 95% CI: 1.07-2.06, P = 0.02) and advanced fibrosis (OR: 1.83, 95% CI: 1.19-2.83, P = 0.006). The minor allele frequency of rs7574865 was significantly lower than that in healthy controls. rs7574865 GG risk carriers expressed lower levels of STAT4 in liver, PBMCs and in NK cells, while NK cells from patients with the risk genotype had impaired STAT4 phosphorylation following stimulation with IL-12/IL-18 and a reduction in secretion of IFN-γ. CONCLUSION: Genetic susceptibility to HBV persistence, hepatic inflammation and fibrosis in Caucasians associates with STAT4 rs7574865 variant. Downstream effects on NK cell function through STAT4 phosphorylation-dependent IFN-γ production likely contribute to these effects.

Current assessment of risk-benefit by regulators: is it time to introduce decision analyses?

Regulatory risk-benefit assessments may overweight small but serious risks relative to benefits. Using terfenadine and torsade de pointes as an exemplar, we illustrate how a different decision may result when outcomes are assessed using quality-adjusted life-years within a decision-analytical framework. The adoption of common measures of health outcome and the use of decision analyses, which will allow uncertainty to be characterized and evidence to be compiled from disparate sources, may inform complex risk-benefit decisions and should be used in conjunction with qualitative assessments.

Patient support and education for promoting adherence to highly active antiretroviral therapy for HIV/AIDS.

BACKGROUND: Adherence to prescribed regimens is required to derive maximal benefit from many highly active antiretroviral therapy (HAART) regimens in people living with HIV/AIDS. OBJECTIVES: To conduct a systematic review of the research literature on the effectiveness of patient support and education to improve adherence to HAART. SEARCH STRATEGY: A systematic search of electronic databases was performed from January 1996 to May 2005. SELECTION CRITERIA: Randomized controlled trials examining the effectiveness of patient support and education to improve adherence to HAART were considered for inclusion. Only those studies that measured adherence at a minimum of six weeks were included. DATA COLLECTION AND ANALYSIS: Study selection, quality assessments and data abstraction were performed independently by two reviewers. MAIN RESULTS: Nineteen studies involving a total of 2,159 participants met criteria for inclusion. It was not possible to conduct a meta-analysis due to study heterogeneity with respect to populations, interventions, comparison groups, outcomes, and length of follow-up. Sample sizes ranged from 22 to 367. The populations studied ranged from general HIV-positive populations to studies focusing exclusively on children, women, Latinos, or adults with a history of alcohol dependence, to studies focusing almost exclusively on men. Study interventions included cognitive behavioral therapy, motivational interviewing, medication management strategies, and interventions indirectly targeting adherence, such as programs directed to reduce risky sexual behaviours. Ten studies demonstrated a beneficial effect of the intervention on adherence. We found that interventions targeting practical medication management skills, those administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. We also found that interventions targeting marginalized populations such as women, Latinos, or patients with a past history of alcoholism were not successful at improving adherence. We were unable to determine whether effective adherence interventions were associated with improved virological or immunological outcomes. Most studies had several methodological shortcomings leaving them vulnerable to potential biases. AUTHORS' CONCLUSIONS: We found evidence to support the effectiveness of patient support and education interventions intended to improve adherence to antiretroviral therapy. Interventions targeting practical medication management skills, those interventions administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence outcomes. There is a need for standardization and increased methodological rigour in the conduct of adherence trials.

Cost-effectiveness of androgen suppression therapies in advanced prostate cancer.

BACKGROUND: The costs and side effects of several antiandrogen therapies for advanced prostate cancer differ substantially. We estimated the cost-effectiveness of antiandrogen therapies for advanced prostate cancer. METHODS: We performed a cost-effectiveness analysis using a Markov model based on a formal meta-analysis and literature review. The base case was assumed to be a 65-year-old man with a clinically evident, local recurrence of prostate cancer. The model used a societal perspective and a time horizon of 20 years. Six androgen suppression strategies were evaluated: diethylstilbestrol (DES), orchiectomy, a nonsteroidal antiandrogen (NSAA), a luteinizing hormone-releasing hormone (LHRH) agonist, and combinations of an NSAA with an LHRH agonist or orchiectomy. Outcome measures were survival, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios. RESULTS: DES, the least expensive therapy, had a discounted lifetime cost of $3600 and the lowest quality-adjusted survival, 4.6 QALYs. At a cost of $7000, orchiectomy was associated with 5.1 QALYs, resulting in an incremental cost-effectiveness ratio of $7500/QALY relative to DES. All other strategies-LHRH agonists, NSAA, and both combined androgen blockade strategies-had higher costs and lower quality-adjusted survival than orchiectomy. These results were sensitive to the quality of life associated with orchiectomy and the efficacy of combined androgen blockade, and they changed little when prostate-specific antigen results were used to guide therapy. Under a wide range of other assumptions, the cost-effectiveness of orchiectomy relative to DES was consistently less than $20 000/QALY. Androgen suppression therapies were most cost-effective if initiated after patients became symptomatic from prostate metastases. CONCLUSIONS: For men who accept it, orchiectomy is likely to be the most cost-effective androgen suppression strategy. Combined androgen blockade is the least economically attractive option, yielding small health benefits at high relative costs.

LOOP-MEDIATED ISOTHERMAL AMPLIFICATION (LAMP): SENSITIVE AND RAPID DETECTION OF SCHISTOSOMA HAEMATOBIUM DNA IN URINE SAMPLES OF EGYPTIAN SUSPECTED CASES.

Schistosomiasis haemalobium is a major endemic parasitic disease in many tropical regions including Egypt. Typical infection results in haematuria, dysuria, anaemia, genital as well as urinary tract lesions, with prospect of kidney damage in complicated cases. In addition, deposited eggs in the tissue, eventually leads to squamous cell carcinoma of urinary bladder in chronically infected individuals. Microscopic detection of excreted ova in urine samples remains the gold standard diagnostic method, in spite of its inherited low sensitivity, inconsistent egg excretion and unreliable results in chronic phase of the disease. Moreover due to pre-requisite for skilled personals and pricey equipment, PCR-based technologies are of limited use especially in low-income endemic countries. So emergence of loop-mediated isothermal DNA amplification (LAMP) seemed a promising technique. Our study evaluated application of LAMP technique in detection of S. haematobium DNA in 69 urine samples of suspected patients for urogenital schistosomiasis, versus conventional urine filtration followed by microscopy ova detection method. Specificity of LAMP was tested using other parasites DNA samples that showed no cross reactivity. Furthermore our results of the calculated diagnostic parameters for sensitivity and specificity for LAMP assay were 100%, with 95% CI (88.78%-100%), and 63.16%, with 95% CI (45.99%-78.19%) respectively, moreover Positive likelihood ratio (LR+) 2.7, and Negative likelihood ratio (LR-) 0.0, which display that LAMP technique is an up-to-date simple, sensitive, diagnostic important tool that could be employed in clinical diagnosis in poorly equipped facilities, as well as in surveillance of infectious diseases. As authors knowledge, this is the first national report evaluation of LAMP technique as a promising diagnostic tool for urogenital schistosomiasis.

Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism.

BACKGROUND: Primordial dwarfism is a state of extreme prenatal and postnatal growth deficiency, and is characterized by marked clinical and genetic heterogeneity. RESULTS: Two presumably unrelated consanguineous families presented with an apparently novel form of primordial dwarfism in which severe growth deficiency is accompanied by distinct facial dysmorphism, brain malformation (microcephaly, agenesis of corpus callosum, and simplified gyration), and severe encephalopathy with seizures. Combined autozygome/exome analysis revealed a novel missense mutation in WDR4 as the likely causal variant. WDR4 is the human ortholog of the yeast Trm82, an essential component of the Trm8/Trm82 holoenzyme that effects a highly conserved and specific (m(7)G46) methylation of tRNA. The human mutation and the corresponding yeast mutation result in a significant reduction of m(7)G46 methylation of specific tRNA species, which provides a potential mechanism for primordial dwarfism associated with this lesion, since reduced m(7)G46 modification causes a growth deficiency phenotype in yeast. CONCLUSION: Our study expands the number of biological pathways underlying primordial dwarfism and adds to a growing list of human diseases linked to abnormal tRNA modification.

Preventing Mycobacterium avium complex in patients who are using protease inhibitors: a cost-effectiveness analysis.

BACKGROUND: Practice guidelines recommending Mycobacterium avium complex (MAC) prophylaxis for patients with HIV disease were based on clinical trials in which individuals did not receive protease inhibitors. OBJECTIVE: To estimate the cost-effectiveness of strategies for MAC prophylaxis in patients whose treatment regimen includes protease inhibitors. DESIGN: Decision analysis with Markov modelling of the natural history of advanced HIV disease. Five strategies were evaluated: no prophylaxis, azithromycin, rifabutin, clarithromycin and a combination of azithromycin plus rifabutin. MAIN OUTCOME MEASURES: Survival, quality of life, quality-adjusted survival, health care costs and marginal cost-effectiveness ratios. RESULTS: Compared with no prophylaxis, rifabutin increased life expectancy from 78 to 80 months, increased quality-adjusted life expectancy from 50 to 52 quality-adjusted months and increased health care costs from $233000 to $239800. Ignoring time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $44300 per life year. Adjusting for time discounting and quality of life, the cost-effectiveness of rifabutin relative to no prophylaxis was $41500 per quality-adjusted life year (QALY). In comparison with rifabutin, azithromycin was associated with increased survival, increased costs and an incremental cost-effectiveness ratio of $54300 per QALY. In sensitivity analyses, prophylaxis remained economically attractive unless the lifetime chance of being diagnosed with MAC was less than 20%, the rate of CD4 count decline was less than 10 x 10(6) cells/l per year, or the CD4 count was greater than 50 x 10(6) cells/l. CONCLUSION: MAC prophylaxis increases quality-adjusted survival at a reasonable cost, even in patients using protease inhibitors. When not contraindicated, starting azithromycin or rifabutin when the patient's CD4 count is between 50 and 75 x 10(6) cells/l is the most cost-effective strategy. The main determinants of cost-effectiveness are CD4 count, viral load, place of residence and patient preference.

Kuwait nutritional survey: comparison of the nutritional status of Kuwaiti children aged 6-9 years with the NCHS/CDC reference population.

A national cross-sectional survey of the heights and weights of Kuwaiti primary school children aged 6-9 years was conducted on a stratified multistage sample of 5132 subjects from two socio-economic districts. The collected data were used to compare the nutritional status of Kuwaiti children with their American counterparts using the NCHS/CDC reference population. The basic indices used for comparison were height for age and weight for height, each considered in terms of centiles and SD scores and cross-classified using SD scores. The results indicated that although Kuwaiti children in the studied age groups are shorter than American children severe short stature is relatively infrequent as 48.3% fell below the 30th centile of the reference population. Conversely, Kuwaiti children are relatively heavier than American children as 61.1% fell above the 50th centile of the reference population.

Adverse drug reaction monitoring in Kuwait (1981-1984).

The methodologic, operational, and medical aspects of general population spontaneous adverse drug reaction (ADR) monitoring system organized in the State of Kuwait between June 1981 to June 1984 are described. The objectives of the study were to outline the procedures required for the establishment of a national ADR center in addition to studying the pattern of ADRs. Ethnic and sociocultural variables were factors influencing the frequency of adverse effects. A computer data base was created to handle incoming reports. A total of 704 reports were received from 26 hospitals and health clinics; the majority (90.5%) were classified as having a possible positive causal relationship. Anti-infectives were the most commonly reported drugs (32.2%), and cutaneous reactions were encountered most often (48.6%). Serious drug-induced reactions have been identified. Intake of nifedipine adversely affected glucose tolerance among diabetic and nondiabetic subjects. Bromocriptine causal sexual dysfunction was reported among women. Cimetidine and ethambutol were associated with optic neuritis and blindness. Metoclopramide and prochlorperazine resulted in dystonic reactions in children. Based on this study, the health authorities in Kuwait indicated their intention to establish a national ADR center.

Hepatitis B virus (HBV) markers among patients with chronic liver disease in Kuwait.

The prevalence of hepatitis B surface antigen (HBsAg), antibody to the hepatitis B core (anti-HBc) and to surface antigen (anti-HBs), was investigated, using sensitive radioimmunoassay (RIA) systems, among patients with different clinical entities of chronic liver disease in Kuwait, and compared to a control blood donor population. 81% of patients and 44% of the controls had at lease one HBV marker. 24% of patients, but non of the controls had both HBsAg and a high titre of anti-HBc in the absence of anti-HBs, suggesting a chronic infection. 31% of our patients with hepatosplenic schistosomiasis, 20% with cryptogenic cirrhosis and chronic active liver disease and 60% with hepatocellular carcinoma had these two markers. HBV antigenaemia was significantly more prevalent among male than among female patients and was particularly high among those less than 35 years old. The high prevalence of the various HBV markers among our patients suggests that HBV is a major factor in the development of chronic liver disease in our area. Furthermore, in view of a high prevalence of antigenaemia in patients with hepato-splenic schistosomiasis, HBV infection must play a concomitant role in the development of more serious form of chronic liver disease among such patients.

Effects of cationic diamidines on polyamine metabolism in the trypanosomatid Crithidia fasciculata.

The effect of a series of five recently synthesized cationic diamidines on cell proliferation and polyamine metabolism was studied on cultures of the model Trypanosomatid Crithidia fasciculata. Compounds displaying two arylic moieties (CGP039937A and CGP040215A) were ten fold more cytostatic than those displaying only one arylic residue (CGP033829A, CGP035753A and CGP036958A). The depletion of intracellular polyamine, putrescine and spermidine, pools and the effect of these compounds on S-adenosylmethionine decarboxylase and putrescine uptake suggest the requirement of two arylic groups in their chemical structure to obtain measurable effects on both polyamine metabolism and cell growth.

Septicaemia in a teaching hospital in Kuwait--II: Factors influencing the outcome in III episodes.

The case fatality rate (CFR) among III episodes of septicaemia in Kuwait was 22.5%. It increased with age but was not influenced by sex. Gram-negative, polymicrobial and hospital-acquired septicaemia carried a high mortality rate. Due to the influence of the more common, but less fatal salmonella infections, however, mortality from septicaemia caused by Gram-negative bacteria was lower than that reported from more developed countries. Patients with underlying conditions, such as malignancy, chronic liver disease, diabetes mellitus, renal transplant and conditions requiring surgery, as well as those with unknown sources of infection or infection originating from the respiratory tract or from surgical wounds had high mortality rates. The chances of survival increased with the use of appropriate antibiotic therapy and the absence of underlying disease. None of the patients with underlying conditions survived after receiving inappropriate therapy as compared with 50% who were previously healthy. The changing aetiology and the emergence of immuno compromised patients are possible causes for the failure to reduce significantly the mortality from septicaemia in Kuwait.

Decision analysis with cumulative prospect theory.

BACKGROUND: Individuals sometimes express preferences that do not follow expected utility theory. Cumulative prospect theory adjusts for some phenomena by using decision weights rather than probabilities when analyzing a decision tree. METHODS: The authors examined how probability transformations from cumulative prospect theory might alter a decision analysis of a prophylactic therapy in AIDS, eliciting utilities from patients with HIV infection (n = 75) and calculating expected outcomes using an established Markov model. They next focused on transformations of three sets of probabilities: 1) the probabilities used in calculating standard-gamble utility scores; 2) the probabilities of being in discrete Markov states; 3) the probabilities of transitioning between Markov states. RESULTS: The same prophylaxis strategy yielded the highest quality-adjusted survival under all transformations. For the average patient, prophylaxis appeared relatively less advantageous when standard-gamble utilities were transformed. Prophylaxis appeared relatively more advantageous when state probabilities were transformed and relatively less advantageous when transition probabilities were transformed. Transforming standard-gamble and transition probabilities simultaneously decreased the gain from prophylaxis by almost half. Sensitivity analysis indicated that even near-linear probability weighting transformations could substantially alter quality-adjusted survival estimates. CONCLUSION: The magnitude of benefit estimated in a decision-analytic model can change significantly after using cumulative prospect theory. Incorporating cumulative prospect theory into decision analysis can provide a form of sensitivity analysis and may help describe when people deviate from expected utility theory.