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Background: Patient-centered decision making, which in the United States is typically considered to be appropriate, may not be universally endorsed, thereby harboring the potential to complicate the care of patients from other cultural backgrounds in potentially unrecognized ways. This study compares the attitudes toward ethical decision making and autonomy issues among academic and community physicians and patients of medical center outpatient clinics in Japan and the United States.Methods: A questionnaire requesting judgments about seven clinical vignettes was distributed (in English or Japanese) to sample groups of Japanese physicians (n = 400) and patients (n = 65) as well as US physicians (n = 120) and patients (n = 60) that were selected randomly from academic institutions and community settings in Japan (Tokyo and the surrounding area) and the United States (the Stanford/Palo Alto, CA, area). Responses were obtained from 273 Japanese physicians (68%), 58 Japanese patients (89%), 98 US physicians (82%), and 55 US patients (92%). Physician and patient sample groups were compared on individual items, and composite scores were derived from subsets of items relevant to patient autonomy, family authority, and physician authority.Results: A majority of both US physicians and patients, but only a minority of Japanese physicians and patients, agreed that a patient should be informed of an incurable cancer diagnosis before their family is informed and that a terminally ill patient wishing to die immediately should not be ventilated, even if both the doctor and the patient's family want the patient ventilated (Japanese physicians and patients vs US physicians and patients, p < 0.001). A majority of respondents in both Japanese sample groups, but only a minority in both US sample groups, agreed that a patient's family should be informed of an incurable cancer diagnosis before the patient is informed and that the family of an HIV-positive patient should be informed of this disease status despite the patient's opposition to such disclosure (Japanese physicians and patients vs US physicians and patients, p < 0.001). Physicians in both Japan and the United States were less likely than patients in their respective countries to agree with physician assistance in the suicide of a terminally ill patient (Japanese physicians and patients vs US physicians and patients, p < 0.05). Across various clinical scenarios, all four respondent groups accorded greatest authority to the patient, less to the family, and still less to the physician when the views of these persons conflicted. Japanese physicians and patients, however, relied more on family and physician authority and placed less emphasis on patient autonomy than the US physicians and patients sampled. Younger respondents placed less emphasis on family and physician authority.Conclusions: Family and physician opinions are accorded a larger role in clinical decision making by the Japanese physicians and patients sampled than by those in the United States, although both cultures place a greater emphasis on patient preferences than on the preferences of the family or physician. Our results are consistent with the view that cultural context shapes the relationship of the patient, the physician, and the patient's family in medical decision making. The results emphasize the need for clinicians to be aware of these issues that may affect patient and family responses in different clinical situations, potentially affecting patient satisfaction and compliance with therapy. [ABSTRACT FROM AUTHOR]

The Eastern Mediterranean Region (EMR) is witnessing an increase in chronic disorders, including mental illness. With ongoing unrest, this is expected to rise. This is the first study to quantify the burden of mental disorders in the EMR. We used data from the Global Burden of Disease study (GBD) 2013. DALYs (disability-adjusted life years) allow assessment of both premature mortality (years of life lost-YLLs) and nonfatal outcomes (years lived with disability-YLDs). DALYs are computed by adding YLLs and YLDs for each age-sex-country group. In 2013, mental disorders contributed to 5.6% of the total disease burden in the EMR (1894 DALYS/100,000 population): 2519 DALYS/100,000 (2590/100,000 males, 2426/100,000 females) in high-income countries, 1884 DALYS/100,000 (1618/100,000 males, 2157/100,000 females) in middle-income countries, 1607 DALYS/100,000 (1500/100,000 males, 1717/100,000 females) in low-income countries. Females had a greater proportion of burden due to mental disorders than did males of equivalent ages, except for those under 15 years of age. The highest proportion of DALYs occurred in the 25-49 age group, with a peak in the 35-39 years age group (5344 DALYs/100,000). The burden of mental disorders in EMR increased from 1726 DALYs/100,000 in 1990 to 1912 DALYs/100,000 in 2013 (10.8% increase). Within the mental disorders group in EMR, depressive disorders accounted for most DALYs, followed by anxiety disorders. Among EMR countries, Palestine had the largest burden of mental disorders. Nearly all EMR countries had a higher mental disorder burden compared to the global level. Our findings call for EMR ministries of health to increase provision of mental health services and to address the stigma of mental illness. Moreover, our results showing the accelerating burden of mental health are alarming as the region is seeing an increased level of instability. Indeed, mental health problems, if not properly addressed, will lead to an increased burden of diseases in the region., Competing Interests: We would like to declare the following commercial affiliations: Dr. Anwar Rafay is employed by Contech International health consultants. Syed Danish Ali is employed by SIR Consultants. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Recurrent invasive ameloblastoma of the infratemporal fossa is an uncommonly encountered phenomenon in the practice of oral and maxillofacial surgery and presents many surgical challenges for the practitioner. This case report describes a patient who underwent previous resection of a mandibular ameloblastoma with multiple recurrences. The patient was diagnosed with a recurrent ameloblastoma of the infratemporal fossa that was subsequently resected and reconstructed using an anterolateral thigh (ALT) free tissue transfer. There are few reported cases of recurrent ameloblastomas in the infratemporal fossa and none that describe surgical resection and reconstruction of such a lesion. Owing to the uniqueness of the surgical defect, an ALT flap was used to correct the temporal hollowing. There have been multiple reported cases of reconstruction of temporal hollowing defects using autogenous fat or allograft; however, none have described the use of a de-epithelialized ALT microvascular reconstruction of a temporal hollowing defect. This case report describes a unique clinical situation of surgical resection and reconstruction that resulted in a satisfactory outcome for the patient., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Importance: The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce., Objective: To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged <5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study., Evidence Review: Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14,244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35,620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates., Findings: Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905.059 deaths; 95% UI, 810,304-998,125), diarrheal diseases among older children (38,325 deaths; 95% UI, 30,365-47,678), and road injuries among adolescents (115,186 deaths; 95% UI, 105,185-124,870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia., Conclusions and Relevance: Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed., Competing Interests: Conflict of Interest Disclosures: Dr. Kassebaum reports personal fees and non-financial support from Vifor Pharmaceuticals, Axon Communications LLC and Merck & Co outside the submitted work. KPG was awarded the NHMRC-Gustav Nossal Postgraduate Award sponsored by CSL; this award is peer reviewed and CSL had no part in selecting the awardee. Prof. Lotufo reports honoraria (modest) from Abbvie for one lecture. Walter Mendoza is program analyst at the UNFPA country office in Peru, which not necessarily endorses the study. Prof. Santos reports receiving a grant from São Paulo Research Foundation/FAPESP (Brazilian governmental research agency) for research purposes. In the past 3 years, Dr. Stein has received research grants and/or consultancy honoraria from AMBRF, Biocodex, Cipla, Lundbeck, National Responsible Gambling Foundation, Novartis, Servier, and Sun. No other conflicts are reported.

Background: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution., Methods: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol., Findings: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa., Interpretation: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks., Funding: Bill & Melinda Gates Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration., Methods: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets., Findings: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990., Interpretation: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action., Funding: Bill & Melinda Gates Foundation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: This literature review assessed the burden of treatment-resistant depression in the United States by compiling published data about the clinical, societal, and economic outcomes associated with failure to respond to one or more adequate trials of drug therapy., Methods: PubMed and the Tufts Cost-Effectiveness Analyses Registry were searched for English-language articles published between January 1996 and August 2013 that collected primary data about treatment-resistant depression. Two researchers independently assessed study quality and extracted data., Results: Sixty-two articles were included (N=59,462 patients). Patients with treatment-resistant depression had 3.8±2.1 prior depressive episodes and illness duration of 4.4±3.3 years and had completed 4.7±2.7 unsuccessful drug trials involving 2.1±.3 drug classes. Response rates for treatment-resistant depression were 36%±1%. A total of 17%±6% of patients had prior suicide attempts (1.1±.2 attempts per patient). Quality-of-life scores (scale of 0-1, with 0 indicating death and 1 indicating perfect health) for patients with treatment-resistant depression were .41±.8 and .26±.8 points lower, respectively, than for patients who experienced remission or response. Annual costs for health care and lost productivity were $5,481 and $4,048 higher, respectively, for patients with treatment-resistant versus treatment-responsive depression., Conclusions: Treatment-resistant depression exacts a substantial toll on patients' quality of life. At current rates of 12%-20% among all depressed patients, treatment-resistant depression may present an annual added societal cost of $29-$48 billion, pushing up the total societal costs of major depression by as much as $106-$118 billion. These findings underscore the need for research on the mechanisms of depression, new therapeutic targets, existing and new treatment combinations, and tests to improve the efficacy of and adherence to treatments for treatment-resistant depression.

Patients with schizophrenia often fail to respond to an initial course of therapy. This study systematically reviewed the societal and economic burden of treatment-resistant schizophrenia (TRS). Studies that described patients with TRS published 1996-2012 were included if they collected primary data on clinical, social, or economic outcomes. All studies were independently reviewed and extracted by at least two investigators. Sixty-five studies were identified. Almost 60% (SD 18%) of patients failed to achieve response after 23 weeks on antipsychotic drug therapy. Patients with TRS had high rates of smoking (56%), alcohol abuse (51%), substance abuse (51%), and suicide ideation (44%). The incidence of severe adverse events to treatment was 4% (SD 7%). Mean quality of life for patients who were unresponsive or intolerant to treatment was ∼20% lower than that of patients in remission. Annual costs for patients with schizophrenia are $15 500-$22 300 and are 3-11-fold higher for patients with TRS. TRS remains common and costly, despite availability of many treatment options, and contributes to a significant loss in patient quality of life. Although estimates in the literature vary greatly, TRS conservatively adds more than $34 billion in annual direct medical costs in the USA.

Patients and payers (government and private) are frustrated with the fee-for-service system (FFS) of payment for outpatient health services. FFS rewards volume and highly valued services, including expensive diagnostics and therapeutics, over lesser valued cognitive services. Proposed payment schemes would incent collaboration and coordination of care among providers and reward quality. In oncology, new payment schemes must address the high costs of all services, particularly drugs, while preserving the robust distribution of sites of service available to patients in the United States. Information technology and personalized cancer care are changing the practice of oncology. Twenty-first century oncology will require increasing cognitive work and shared decision making, both of which are not well regarded in the FFS model. A high proportion of health care dollars are consumed in the final months of life. Effective delivery of palliative and end-of-life care must be addressed by practice and by new models of payment. Value-based reimbursement schemes will require oncology practices to change how they are structured. Lessons drawn from the principles of primary care's Patient Centered Medical Home (PCMH) will help oncology practice to prepare for new schemes. PCMH principles place a premium on proactively addressing toxicities of therapies, coordinating care with other providers, and engaging patients in shared decision making, supporting the ideal of value defined in the triple aim-to measurably improve patient experience and quality of care at less cost. Payment reform will be disruptive to all. Oncology must be engaged in policy discussions and guide rational shifts in priorities defined by new payment models.

Purpose: The primary tissue-site origin in over 4% of cancers remains uncertain despite thorough clinicopathological evaluation. This study assessed the effect of a Food and Drug Administration-cleared 2,000- gene-expression-profiling (GEP) test on primary tissue-site working diagnoses and management for metastatic and poorly differentiated cancers., Methods: Clinical information was collected from physicians ordering the GEP test for patients with difficult to diagnose cancers. Endpoints included diagnostic procedures, physicians' working diagnoses and treatment recommendations before and after GEP result availability, and physician reports of the test's usefulness for clinical decision making. Patient date of death was obtained, with a minimum of one year follow-up from date of biopsy., Results: Sixty-five physicians participated in the study (n=107 patients). Before GEP, patients underwent 3.2 investigations on average (e.g., radiology, endoscopy). Ten immunohistochemistry tests were used per biopsy (SD 5.2). After GEP testing, physicians changed the primary working diagnosis for 50% of patients (95% CI: 43%,58%) and management for 65% of patients (95% CI: 58%,73%). With GEP results, the recommendation for guideline-consistent chemotherapy increased from 42% to 65% of patients, and the recommendation for non-guideline-consistent regimens declined from 28% to 13%. At last follow-up, 69 patients had died, and median survival was 14.0 months (95% CI: 10.2,18.6). Thirty-three percent of patients were alive at 2 years., Conclusion: In patients with difficult-to-diagnose cancers, GEP changed the working diagnosis and management for the majority of patients. Patients for whom the GEP test was ordered had longer median survival than that historically reported for patients enrolled in treatment trials for cancer of unknown primary.

Background: Findings from the Groupe d'Etude des Lymphomes Adultes LNH 98-5 study showed that rituximab added to combined cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) prolonged progression-free survival and overall survival in adults age >/= 60 years with diffuse large B-cell non-Hodgkin lymphoma (DLBCL). The current study was conducted to investigate the incremental cost utility of the addition of rituximab to CHOP (R-CHOP) compared with CHOP alone., Methods: Clinical prognosis of the time to disease progression and death was estimated using published evidence from the LNH 98-5 study (n = 399 patients) that was linked mathematically to published long-term outcome data on patients with DLBCL. Drug-acquisition costs were based on published data from formulary pricing sources, and the costs of cancer surveillance and end-of-life care were based on published literature sources. The authors assessed cost utility as the difference in costs between R-CHOP and CHOP divided by the increase in expected overall survival adjusted for quality of life., Results: Over 5 years, it was projected that R-CHOP would prolong overall survival by 1.04 years. The mean cumulative cost of CHOP was 3358 dollars, and the mean cost of R-CHOP was 17,225 dollars, resulting in a cumulative net increase of 13,867 dollars. The posttreatment cancer surveillance cost for CHOP was 3950 dollars, compared with 5202 dollars for R-CHOP. It was estimated that R-CHOP would have a cost-utility ratio of 19,297 dollars per year of life gained compared with CHOP when adjusted for quality of life. R-CHOP remained cost effective over wide ranges of variables in sensitivity analyses., Conclusions: Compared with CHOP alone, it was predicted that R-CHOP would be cost effective in elderly patients with DLBCL., ((c) 2005 American Cancer Society.)

The constraints on medical-care resources can give rise to the question of the cost-effectiveness of permitting repeat medical procedures when some patients may die without undergoing even a first procedure. Using kidney transplantation as an example, this study estimates the cost-effectiveness of patients' having available the option of a repeat medical procedure in the event the first procedure fails. Specifically, the analysis examines the effect on transplant candidates of having the option of kidney retransplantation, if and when retransplantation might be needed. Data sources include the U.S. Renal Data System (USRDS) Case-Mix Severity Study, Health Care Financing Administration (HCFA) data, and a MEDLINE search. Outcome measures include life expectancy, quality-adjusted life expectancy, lifetime costs of medical care, and marginal cost-effectiveness from a societal perspective. By avoiding lifelong dialysis after graft failure, first-transplant candidates gain an average of 47 quality-adjusted days with a retransplantation policy, despite the prolongation of time to first transplant by an average of 30 quality-adjusted days. The lifetime cost of medical care per first-transplant candidate is $1,210 higher with a retransplantation policy compared with the no-retransplantation policy; its societal cost-effectiveness is estimated to be $9,656 per quality-adjusted life-year saved. The retransplantation policy provides the greatest improvement in quality-adjusted life expectancy for younger candidates. In the case of kidney transplantation, the cost-effectiveness of a repeat transplant, on average, compares favorably with those of other medical strategies in common practice. As resources become increasingly constrained, this study demonstrates a framework for considering the cost-effectiveness of repeat medical procedures.

Objectives: National registry data suggest that mortality rates among patients with end-stage renal disease are lower in Canada than in the United States. Casemix and treatment variables, although limited in such instances, do not explain this difference. Using a more complete set of casemix and treatment variables from clinical databases, this study assesses mortality, hospital admission, and the cost of medical care for patients with end-stage renal disease treated in Manitoba, Canada and the United States., Methods: Mortality rates were compared in patients with end-stage renal disease treated in the Province of Manitoba and a random sample of US patients enrolled in the US Renal Data System Casemix Severity Study. Hospital admission rates and costs of care were compared in Manitoba patients and in patients with end-stage renal disease in a large health care organization in Detroit, Michigan., Results: Levels of serum creatinine, urea, and estimated glomerular filtration rate indicated more severe renal impairment at the outset of treatment in Manitoba than in the United States. Manitoba patients were more than twice as likely to receive kidney transplants as US Renal Data System patients. No patients in Manitoba used reprocessed dialyzers, compared with 57% of US Renal Data System patients. After adjustment for all casemix and treatment variables, the mortality rate was 47% higher in the United States. The hospital admission rate in Detroit was 41% lower than the hospital admission rate in Manitoba, which primarily reflects the doubled rate of transplantation in Manitoba. Adjusted total monthly costs were $503 higher in Detroit than in Manitoba., Conclusions: The higher mortality rates in the United States cannot be fully explained by adjustments for observable casemix or treatment variables. Further research is needed to identify factors that explain how Manitoba achieves a lower mortality rate while paying less for end-stage renal disease care than the United States.

Objectives: More than 31 million persons living in the United States do not speak English, therefore language discordance between the clinician and patient may hinder delivery of cost-effective medical care. A new language service was developed in which interpreters are trained in the skills of simultaneous interpretation commonly used at international conferences. The interpreters are linked from a remote site to headsets worn by the clinician and patient through standard communication wires. The service is called "remote-simultaneous interpretation," to contrast it with a traditional method of an interpreter being physically present at the interview and interpreting consecutively "proximate-consecutive interpretation." The aim of this study is to assess in a randomized protocol the quality of communication, interpretation, and level of patient, interpreter, and physician satisfaction with these two language services., Methods: The first postpartum visit with each of 49 mothers and their new born babies was assigned randomly to proximate-consecutive interpretation (control) or to remote-simultaneous interpretation (experimental). Main outcome measures included (1) the number of physician and mother utterances in the visit, (2) the quality of the interpretation, and (3) physician, interpreter, and mother preferences between the two services., Results: The remote-simultaneous interpreter service averaged 8.3 (10%) more physician utterances (95% confidence interval [CI] 4.3, 12.4) and 9.1 (28%) more mother utterances (95% CI 6.1, 12.1). On average, there were 2.8 (12%) fewer inaccuracies of physician utterances in experimental visits compared with control visits (95% CI -5.9, 0.4) and 3.0 (13%) fewer inaccuracies of mother utterances in experimental visits compared with control visits (95% CI -5.4, -0.6). Mothers and physicians significantly preferred the remote-simultaneous service to proximate-consecutive interpretation service. Interpreters stated that they thought mothers and physicians better understood each other using the remote-simultaneous service, although the interpreters preferred to work with the proximate-consecutive service., Conclusions: Using remote-simultaneous interpretation to improve the quality of communication in discordant-language encounters promises to enhance delivery of medical care for the millions of non-English-speaking patients in the United States.

A patient's quality of life is difficult to assess. Most methods designed to evaluate quality of life for clinical trials are time consuming, subject to varied interpretation among patients and assessors, and apply scales with only a limited relationship to utility theory. We have developed a HyperCard program, incorporating animated graphics, to (1) improve the speed of collection and collation of data, (2) improve understanding between patients and assessors, and (3) incorporate utility theory-based assessments. We assessed the quality of life of 25 patients with end-stage renal disease receiving hemodialysis using a traditional paper-based presentation and, eight months later, repeated the assessment with a computer-assisted presentation. Each presentation incorporated five techniques for evaluating quality of life: the Campbell Index of Well-being, the Kaplan-Bush Index of Well-being, categorical scaling, standard gamble, and time tradeoff. The computer program improved the speed of collation of data for statistical analysis, provided a consistent interface among patients for utility assessments, and showed stable reporting of patient's well-being. These findings suggest that further development of computer-assisted assessments of patients' quality of life for clinical trials is warranted.

Researchers and administrators must decide which clinical trials are worth doing and how many subjects are needed for a trial. We calculated sample size considering the costs of implementing the results of the trial and the trial costs using (1) Neyman-Pearson methods and (2) a Bayesian cost-benefit method. We illustrate these methods in a clinical trial sponsored by the National Institutes of Health that compares two levels of blood urea nitrogen clearance by haemodialysis for patients with end-stage renal disease. When applied to evaluations of research proposals, these methods may help researchers to decide whether to begin a study, and, if so, how many subjects to enrol in it. These methods should be especially useful for large studies intended to inform health policy.

Involving patients in their health care decisions improves patient satisfaction and outcomes, but can be costly because of the materials and time needed to discuss the many issues that constitute a medical problem. The authors present a framework for identifying the minimum data needed on patient preferences for accurate medical decision making. The method is illustrated for the decision of whether patients with end-stage renal disease should undergo short or long hemodialysis treatments. The value of health states to patients was modeled as a function of six outcomes: survival, uremic symptoms, hospital days per year, the inconvenience associated with long dialysis treatment duration, presence of hypotension during dialysis, and presence of other symptoms during dialysis. The relative importance of each outcome was characterized in a value function by weights referred to as preference-scaling factors. These factors were varied at random over a uniform distribution to simulate different patterns of patient preferences on the six outcomes. The decision model's recommendation was recorded for each simulation. Classification and regression-tree (CART) and stepwise logistic regression analyses were applied to these recommendations to determine the scaling-factor levels that predict short or long treatments. Knowledge of scaling factors on only the inconvenience of long dialysis treatment duration, the worst alive state of health on hemodialysis, and presence of hypotension identified the correct treatment in more than 97% of simulations. Fifty-five patients undergoing hemodialysis were then surveyed for their scaling factors on the six dimensions of well-being. When patients' scaling factors were applied to the predictive rule generated by CART using simulated scaling factors, more than 94% of treatment decisions were classified correctly--sensitivity and specificity of predicting long dialysis were 89% and 100%, respectively. These statistical techniques applied to results of a decision model help identify the minimum data needed on patient preferences to involve patients in efficient and accurate decisions about their health care.

High-flux dialysis is a new method for providing routine-maintenance hemodialysis to patients with end-stage renal disease. It promises to shorten the duration of the dialysis session, but poses potential clinical risks to patients and financial risks to dialysis centers because of the high unit cost of purchasing new dialysis equipment. We retrospectively evaluated the cost-effectiveness of high-flux dialysis compared to conventional dialysis in a hospital-based center. The center provided only conventional dialysis until March 1989, when it initiated high-flux dialysis. The estimated annual costs of treatment were US $31,249 (high-flux) and $32,562 (conventional). The rate of hospital admissions was almost identical in both groups (conventional, 1.29 admissions per year; high-flux, 1.24 admissions per year; p = 0.23). Predicted prolongation of life expectancy with high-flux dialysis was significantly higher after statistical adjustment for observable patient characteristics (1.8 to 4.5 years; p < 0.01). The cost-effectiveness ratio was $28,188 per life-year saved for high-flux compared to conventional dialysis. These findings suggest that the added capital expense of purchasing high-flux equipment can be justified from the perspective of its societal cost-effectiveness.

Case-mix adjusted mortality rates for patients undergoing hemodialysis for ESRD increased during the 1980s, despite the introduction of advanced dialysis technologies. Variations in dialysis practices suggest that excess mortality may be caused by inadequate uremic-toxin clearances. Cost-effectiveness analysis was used to assess whether attempts to improve uremic-toxin clearance are cost effective, assuming that these therapies are clinically effective. The medical literature was surveyed by the use of MEDLINE to assess the likelihood of clinical outcomes on the basis of the type of treatment given to the patient. Options considered in the model were delivered fractional urea clearance (Kt/V), dialysis-treatment duration, type of dialyzer membrane, dialysate, and ultrafiltration. Clinical outcomes included in the model were survival, severity of uremic symptoms, hospital days per year, and intradialytic hypotension and symptoms. Lifetime costs were calculated from data collected from a northern California dialysis center and abstracted from the literature. In the base-case scenario, it was assumed that increasing Kt/V to levels greater than 1 was effective in reducing morbidity and mortality. Under these assumptions, outpatient cost increased significantly, but the cost effectiveness of Kt/V equal to 1.5 was less than $50,000 per quality-adjusted life-year saved. These calculations indicate that, if higher levels of Kt/V prove clinically effective, they are also cost effective.

What comprises an optimal prescription for uremictoxin clearance in the chronic hemodialysis setting is a much disputed issue. The dispute is underscored by the rise in mortality of the U.S. dialysis population during the 1980s and reports of significant noncompliance with minimal treatment standards recommended from the National Cooperative Dialysis Study. A decision model was developed to summarize and test assumptions about the effect of various dialytic-treatment options on patient outcomes. Treatment options included delivered fractional urea clearance (Kt/V), dialysis-treatment duration, dialysis membrane (high flux versus conventional), dialysate (bicarbonate versus acetate), and ultrafiltration (controlled versus uncontrolled). The expected outcome for any set of treatment options was calculated as a function of a representative patient's life expectancy, adjusted for the probability and assumed importance of avoiding uremia- and treatment-related complications, referred to as quality-adjusted life expectancy (QALE). QALE increased by 59 days for each 0.1-U increase in Kt/V and by 187 days with high-flux dialysis. Controlled ultrafiltration with bicarbonate dialysis increased QALE by 30 days compared with uncontrolled ultrafiltration with acetate dialysis. Sensitivity analyses showed that, under conservative assumptions, QALE increased 11 days for every 0.1 increment in Kt/V. The model afforded a framework for reviewing the literature and testing assumptions about the expected benefits of dialytic-treatment options for the development of a clinical guideline on the adequacy of dialysis.

The use of high-flux dialysis in clinical practice increased rapidly despite an absence of reports on the clinical effectiveness of the technique. Mortality and hospital admission rates of patients treated with high-flux dialysis were evaluated and compared with those of patients treated with conventional dialysis in a hospital-based renal dialysis unit in northern California. By use of a retrospective, cross-over design, 253 patients enrolled in the dialysis unit from January 1987 to January 1991 were studied. During this period, 107 patients were treated with high-flux dialysis for at least 1 month, and all but 17 of them had received conventional dialysis before switching to high-flux dialysis. The remaining 146 patients were treated with only conventional dialysis. Of the 80 patients who died during the study period, 69 were receiving conventional dialysis and 11 were receiving high-flux dialysis. The multivariate analyses, adjusted for age, gender, ethnic background, type of renal failure, comorbid conditions, and duration of ESRD, showed that annual mortality was substantially less for patients treated with high-flux dialysis compared with that for patients treated with conventional dialysis (7 versus 20%; P < 0.001). The difference in the rate of hospital admissions was not statistically significant. In this nonexperimental study, methods were applied to control for selectivity bias and other factors that might confound the apparent treatment effect. The findings suggest that the potential benefits of high-flux dialysis are sufficient to justify further confirmation in a randomized, controlled trial.

Cost-effectiveness analysis is emerging as an approach for determining the relative value of health care programs, technologic innovations, and clinical decisions. Increasingly, patients' stated values for quality of life are applied as adjustment in these analyses; the results may vary depending on how individuals assess their well-being. We interviewed 58 patients with chronic renal failure to determine the level of agreement among six methods for assessing well-being, and to determine the effects of variation in assessed well-being on the results of a cost-effectiveness analysis of in-center hemodialysis. Patients reported well-being using the Sickness Impact Profile, Campbell Index of Well-being, Kaplan-Bush Index of Well-being, categorical scaling, standard gamble, and time trade-off. We found that patient well-being was substantially higher as evaluated by the Sickness Impact Profile compared to the other five methods. The Sickness Impact Profile and the Kaplan-Bush Index of Well-being provided much narrower distributions of assessed values relative to other measures. Correlations among assessment methods were poor (Spearman rank-correlation coefficients range: 0.094-0.519). Discrepancies among indices were particularly vivid when we evaluated data at the individual level; many patients reported a high level of well-being according to one index and a low level of well-being according to a different index. The cost effectiveness of in-center hemodialysis varied from $34,893 to $45,254 per quality-adjusted life-year saved according to the Sickness Impact Profile and standard-gamble technique respectively. The substantial variability in patients' stated quality of life may preclude the use of a single method to analyze the cost effectiveness of a health program.

Serum levels of prostate-specific antigen have assumed a prominent clinical role in the management of prostate cancer. Little is known about the production of prostate-specific antigen, its mechanism of entry into the serum in normal and pathologic states, and mechanism(s) of removal from the serum. This study examined nephrostomy urine specimens, finding no significant excretion of prostate-specific antigen into the renal pelvic urine. Similarly, no significant lowering of serum prostate-specific antigen levels occurred during routine hemodialysis in men with chronic renal failure, nor were ambulatory, pre-dialysis serum prostate-specific antigen levels in these same men with chronic renal failure elevated. It appears unlikely that the kidney plays a significant role in the clearance of prostate-specific antigen from human serum.

The purpose of this study was to test the utility of upper and lower extremity performance, grip strength, and mental status as predictors of stability or chronic deterioration in a cohort of frail older persons. The study population consisted of a random sample of forty patients selected from residents of an intermediate level care facility. Demographic information, manual ability, mental status, grip strength, mobility, active and resolved medical problems, medications, and professional's estimate of each participant's likelihood of requiring skilled nursing care were obtained within 2 weeks after identifying the sample. Manual ability, mental status, grip strength, and mobility were included in a Performance Index to predict functional ability. Study participants were followed for 2 years to observe which individuals remained at the intermediate care level and which persons required transfer to skilled nursing care. Of the 27 persons who completed the study, 21 persons remained stable (Group 1) and 6 individuals were transferred to skilled nursing care (Group 2) over the 2 year follow-up period. Group comparisons of the mean values revealed statistically significant differences for age, manual ability and the Performance Index. The Performance Index was a statistically significant predictor of increasing dependency (p less than 0.005). Within Group 1, no patients had a performance score which suggested a poor outcome; only one person in Group 2 had a prediction of the favorable outcome. Professional judgement correctly predicted 16 of the 21 persons in Group 1 and 2 of the 6 persons in Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

In normal mammalian aging there is a reduction of cholinergic markers in a variety of regions. To determine whether this reduction is related to reduced numbers of basal forebrain cholinergic neurons, we counted the number and measured the sizes of the magnocellular acetylcholinesterase-positive neurons in this region of 7, 15, and 53-month-old C57Bl/6NNIA mice. Data were collected from coded slides containing the medial septum, nucleus of the diagonal band, magnocellular preoptic nucleus, and nucleus basalis magnocellularis. There was no decline in numbers of basal forebrain acetylcholinesterase-positive neurons in any of the regions studied. However, cell sizes showed a progressive age-related decline which was greatest in the nucleus basalis magnocellularis.