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Globally, land and seascapes across the bioculturally diverse tropics are in transition. Impacted by the demands of distant consumers, the processes of global environmental change and numerous interventions seeking climate, conservation and development goals, these transitions have the potential to impact the relationships and plurality of values held between people and place.This paper is a Synthesis of seven empirical studies within the Special Feature (SF): 'What is lost in transition? Capturing the impacts of conservation and development interventions on relational values and human wellbeing in the tropics'. Through two Open Forum workshops, and critical review, contributing authors explored emergent properties across the papers of the SF. Six core themes were identified and are subsumed within broad categories of: (i) the problem of reconciling scale and complexity, (ii) key challenges to be overcome for more plural understanding of social dimensions of landscape change and (iii) ways forward: the potential of an environmental justice framework, and a practical overview of methods available to do so.The Synthesis interprets disparate fields and complex academic work on relational values, human well‐being and de‐colonial approaches in impact appraisal. It offers a practical and actionable catalogue of methods for plural valuation in the field, and reflects on their combinations, strengths and weaknesses.The research contribution is policy relevant because it builds the case for why a more plural approach in intervention design and evaluation is essential for achieving more just and sustainable futures, and highlights some of the key actions points deemed necessary to achieve such a transition to conventional practice. Read the free Plain Language Summary for this article on the Journal blog. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

The recent ONS survey reported that 92% of students had been affected by the cost-of-living crisis with 46% revealing their overall mental health and well-being had worsened(1). London Metropolitan University has a unique diverse student population: in 2020-21, 82% of students were mature, 64% of students identified as female, 55% of students were from a minoritised background and 13% had a known disability(2). Furthermore, at least 50% of our students, many of whom have caring responsibilities, reside in the most deprived wards of Islington or other impoverished London boroughs. It has been documented that those students with families, who come from a low income and a minority background are more vulnerable(3) and are more likely to be disproportionately affected by the cost-of-living crisis and at risk of food insecurity. We sought to ease the burden of the cost-of-living crisis with a recipe box scheme, BRITE Box (4) and evaluate its acceptance. BRITE Box provides a complete set of pre-weighed ingredients for a healthy nutritious meal with an easy-to-follow recipe guide. Each box typically contains two servings of vegetables, meat, bread and dairy, as well as spices, dried and tinned goods to feed a family of five people. We distributed 300 boxes over a period of five months to students primarily with families who had accessed the university hardship fund. Student volunteers and the academic staff pre-weighed the ingredients, prepared and distributed the boxes. The scheme was advertised through Student Services who administer the hardship fund, the Student Union and the intranet. The recipients of the boxes were provided with a QR code linking to a 20-item online survey on demographic characteristics, number of children, acceptability of the box and perceived advantages and disadvantages of the scheme. Ethics was approved by London Metropolitan University. Thirty-three participants completed the survey, 42% of the recipients identified as female, 55% were from a minority background and 30% had children. The responses showed that students agreed and strongly agreed that the recipe box introduced them to new flavours (52%), and new foods (42%). The majority followed the recipe and will use again (67%). Most importantly, 73% students agreed and or strongly agreed that it helped with the food budget and helped foster a sense of belonging to the university (85%). The scheme has proved to be popular among the students: "a really cool concept", "it helped me cook", "the box provided food for 3 days" and created a buzz around campus on distribution days. It has enhanced the feeling of community and belonging within the university, whilst also alleviating food insecurity and tackling the cost-of-living crisis. [ABSTRACT FROM AUTHOR]

Ruddy shelduck migrate from wintering grounds in lowland India and Myanmar to breeding grounds in central China and Mongolia, sustaining flight over the Himalayas, where oxygen availability is greatly reduced. We compared phenotypes of the pectoralis muscle and the ventricle of the heart from ruddy shelduck and common shelduck (a closely related low-altitude congener) that were raised in common conditions at sea level, predicting that oxidative capacity would be greater in ruddy shelduck to support high-altitude migration. Fibre-type composition of the pectoralis and the maximal activity of eight enzymes involved in mitochondrial energy metabolism in the pectoralis and heart, were compared between species. Few differences distinguished ruddy shelduck from common shelduck in the flight muscle, with the exception that ruddy shelduck had higher activities of complex II and higher ratios of complex IV (cytochrome c oxidase) and complex II when expressed relative to citrate synthase activity. There were no species differences in fibre-type composition, so these changes in enzyme activity may reflect an evolved modification in the functional properties of muscle mitochondria, potentially influencing mitochondrial respiratory capacity and/or oxygen affinity. Ruddy shelduck also had higher lactate dehydrogenase activity concurrent with lower pyruvate kinase and hexokinase activity in the left ventricle, which likely reflects an increased capacity for lactate oxidation by the heart. We conclude that changes in pathways of mitochondrial energy metabolism in the muscle and heart may contribute to the ability of ruddy shelduck to fly at high altitude. [ABSTRACT FROM AUTHOR]

Abstract: Aim: We examined the effects of chronic hypoxia on diaphragm function in high‐ and low‐altitude populations of Peromyscus mice. Methods: Deer mice (P. maniculatus) native to high altitude and congeneric mice native to low altitude (P. leucopus) were born and raised in captivity to adulthood and were acclimated to normoxia or hypobaric hypoxia (12 or 9 kPa, simulating hypoxia at 4300 and 7000 m) for 6‐8 weeks. We then measured indices of mitochondrial respiration capacity, force production, and fatigue resistance in the diaphragm. Results: Mitochondrial respiratory capacities (assessed using permeabilized fibres with single or multiple inputs to the electron transport system), citrate synthase activity (a marker of mitochondrial volume), twitch force production, and muscle fatigue resistance increased after exposure to chronic hypoxia in both populations. These changes were not well explained by variation in the fibre‐type composition of the muscle. However, there were several differences in diaphragm function in high‐altitude mice compared to low‐altitude mice. Exposure to a deeper level of hypoxia (9 kPa vs 12 kPa) was needed to elicit increases in mitochondrial respiration rates in highlanders. Chronic hypoxia did not increase the emission of reactive oxygen species from permeabilized fibres in highlanders, in contrast to the pronounced increases that occurred in lowlanders. In general, the diaphragm of high‐altitude mice had greater capillary length densities, produced less force in response to stimulation and had shorter relaxation times. The latter was associated with higher activity of sarcoplasmic reticulum Ca2+‐ATPase (SERCA) activity in the diaphragm of high‐altitude mice. Conclusion: Overall, our work suggests that exposure to chronic hypoxia increases the capacities for mitochondrial respiration, force production and fatigue resistance of the diaphragm. However, many of these effects are opposed by evolved changes in diaphragm function in high‐altitude natives, such that highlanders in chronic hypoxia maintain similar diaphragm function to lowlanders in sea level conditions. [ABSTRACT FROM AUTHOR]

The Ububele Baby Mat Service is a community-based, parent–infant mental health intervention offered at five primary health care clinics in Alexandra Township, in Johannesburg. The aim of the intervention is to promote healthy caregiver-infant attachments. There has been a steady increase in the number of mother-baby dyads making use of the service. This paper aims to explore how the Baby Mat Service and Baby Mat practitioners position and locate themselves in a culturally diverse community setting where multiple meaning systems are drawn on for making sense of health concerns. Two key components of the Baby Mat Service are discussed: i) the presence of an inter-racial therapeutic couple on the mat; and ii) the stance adopted by the Baby Mat practitioners in relation to culturally diverse understandings of a presenting problem. The therapeutic couple engages with culturally-informed frames of reference in an attitude of wondering and tentative thinking (“mhlawumbe”in isiZulu). When a respectfully curious stance was taken by practitioners, it was found to help those accessing the mat to find symbolic meaning in the presenting problem and integrate this with cultural understandings. [ABSTRACT FROM PUBLISHER]

Background: Papillary lesions of the breast are a relatively rare, but heterogeneous group ranging from benign to atypical and malignant. Debate exists regarding the optimal management of these lesions. In the absence of more accurate risk-stratification models, traditional management guidelines recommend surgical excision, despite the majority of lesions proving benign. This study sought to determine the rate of malignancy in excised breast papillomas and to elucidate whether there exists a population in which surgical excision may be unnecessary. Methods: A multicenter international retrospective review of core biopsy diagnosed breast papillomas and papillary lesions was performed between 2009 and 2013, following institutional ethical approval. Patient demographics, histopathological, and radiological findings were recorded. All data was tabulated, and statistical analysis performed using Stata. Results: A total of 238 patients were included in the final analysis. The age profile of those with benign pathology was significantly younger than those with malignant pathology ( p < 0.001). Atypia on core needle biopsy was significantly associated with a final pathological diagnosis of malignancy (OR = 2.73). The upgrade rate from benign core needle biopsy to malignancy on the final pathological sample was 14.4 %; however, only 3.7 % had invasive cancer. Conclusions: This international dataset is one of the largest in the published literature relating to breast papillomas. The overall risk of malignancy is significantly associated with older age and the presence of atypia on core needle biopsy. It may be possible to stratify higher-risk patients according to age and core needle biopsy findings, thereby avoiding surgery on low-risk patients. [ABSTRACT FROM AUTHOR]

The article discusses the challenges faced by obstetricians which involved decisions that balance competing risks and benefits for fetuses, infants and mothers. The current recommendation to avoid delivery before 39 weeks addresses only one aspect of the decision which is based on minimizing neonatal morbidity and mortality seen with earlier delivery. An aggregated observational data must not be assumed to be enough proxy for individual or subgroup-specific risk.

The article sheds light on the judicial perspectives regarding the rank of Queen's Counsel in creating litigation in modern context. It also discusses the Canadian Privy Council case of Attorney-General for Canada v. Attorney-General for Ontario. It highlights several issues that were raised in the case such as the appointment of Queen's Counsel under the prerogative conferment of honors, duty to act for the Crown, and unlawful selection of Queen's Counsel.

Protection of human participants is a fundamental facet of biomedical research. We report the activities ofa health service research study in which there were three institutional review boards (IRBs), three legaldepartments and one research administration department providing recommendations and mandating changes in the study methods. Complying with IRB requirements can be challenging, but can also adversely affect study outcomes. Multiple protocol changes mandated from multiple IRBs created a research method that was not reflective of how substance use screening would be performed in a clinical setting. There was direct conflict between the IRBs' perceptions of participants' protection with the researchers' need to use research methodology that assures the clinical relevancy of results. [ABSTRACT FROM AUTHOR]

South Africa holds more than 70% of the world's viable chromite ore reserves and produces ~46.2% of the world's high carbon ferrochrome. It was recently reported that beneficiated South African chromite ores contained significant amounts of Cr(VI). If this is true, it could have serious consequences for South African chromite mines and the local environment. Currently none of these mines make any provision for Cr(VI) leaching from their mined ores. The data obtained in this study proved that the Cr(VI) content of chromite samples is influenced by the sample preparation technique employed prior to chemical analysis, more specifically, that pulverising of chromite samples in a normal atmospheric environment resulted in Cr(VI) formation. No Cr(VI) was liberated when pulverising was conducted in an inert atmosphere. The presence of Cr(VI) in South African chromite ores therefore seems unlikely. The results also suggest that the perceived threat of Cr(VI) contamination of groundwater and surface water, originating from chromite ore stockpiles, is improbable. [ABSTRACT FROM AUTHOR]

At this point in time, the only possibility of curing prostate cancer is through the early detection and treatment of localized disease. The large number of treatment options available for localized prostate cancer, including radical prostatectomy, radiotherapy (either external beam or interstitial), hormone therapy and watchful waiting, can be confusing for the patient. These treatments are associated with different adverse effects, further complicating the treatment decision. As there will inevitably be a trade-off between expected cure and acceptable adverse effects, it is important to discuss all options with the patient. The doctor and patient must together decide the appropriate treatment for him and his tumor. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study investigated the effect of alcohol-related disease on hip fracture and mortality. METHODS: A retrospective cohort design was used. The study cohort consisted of hospitalized Medicare beneficiaries with alcohol-related disease (n = 150,119) and randomly matched controls without alcohol-related disease (n = 726,218) identified through the 1988-1989 inpatient claims file. Incidence rates of hip fracture and mortality were examined. RESULTS: During the study period, 20,620 patients developed hip fracture, with 6973 cases among patients with alcohol-related disease and 13,647 cases among patients without alcohol-related disease. After adjustment for potential confounders, patients with alcohol-related disease had a 2.6-fold increased risk of hip fracture relative to patients without alcohol-related disease (95% confidence interval = 2.5, 2.6). Patients with alcohol-related disease had a higher risk of mortality at 1 year after hip fracture. CONCLUSIONS: Alcohol-related disease increases the risk of hip fracture significantly and reduces long-term survival. The present results suggest that patients hospitalized for alcohol-related disease should be targeted for hip fracture prevention programs. [ABSTRACT FROM AUTHOR]

The Mexican axolotl (Ambystoma mexicanum) provides an excellent model for studying heart development since it carries a cardiac lethal mutation in gene c that results in failure of contraction of mutant embryonic myocardium. In cardiac mutant axolotls (c/c) the hearts do not beat, apparently because of an absence of organized myofibrils. To date, there has been no way to analyze the genotypes of embryos from heterozygous spawnings (+/c×+/c) until stage 35 when the normal (+/c or +/+) embryos first begin to have beating hearts; mutant (c/c) embryos fail to develop normal heartbeats. In the present study, we created chimeric axolotls by using microsurgical techniques. The general approach was to transect tailbud embryos and join the anterior and posterior halves of two different individuals. The chimeric axolotl is composed of a normal head and heart region (+/+), permitting survival and a mutant body containing mutant gonads (c/c) that permits the production of c/c mutant offspring: 100% c/c offspring were obtained by mating c/c chimeras (c/c×c/c). The mutant phenotypes were confirmed by the absence of beating hearts and death at stage 41 in 100% of the embryos. Examination of the mutant hearts with electron microscopy and comfocal microscopy after immunofluorescent staining for tropomyosin showed identical images to those described previously in naturally-occurring c/c mutant axolotls (i.e., lacking organized sarcomeric myofibrils). These ”c/c chimeric” axolotls provide a useful and unique way to investigate early embryonic heart development in cardiac mutant Mexican axolotls. [ABSTRACT FROM AUTHOR]

Emergency contraception can be used as a back up if unprotected intercourse occurs or contraception fails. Personal, social and health education (PSHE) co-ordinators may be in a position to provide information about emergency contraception in school in a health promotion context, and for individual pupils. Little is known about what these teachers know about emergency contraception, and whether they see their role as providing pupils with information about it. This paper reports on a survey of PSHE co-ordinators in Avon, South West England. Respondents did believe that it is their responsibility to teach about contraception (80 per cent), including emergency contraception (69 per cent). The results suggest that there are gaps in respondents' knowledge: 85 respondents (98 per cent) knew of hormonal emergency contraception but knowledge of the correct time limits (72 hours) were known to only 65 per cent of respondents. There is a wide range of intended practices in the giving of confidential information to individual pupils. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggest that specialty care is more costly but may produce improved outcomes for patients with acute cardiac illnesses.Objective: To determine whether patients with congestive heart failure who are cared for by cardiologists experienced differences in costs, care patterns, and survival compared with patients of generalists.Design: Prospective cohort study.Setting: 5 U.S. teaching hospitals between 1989 and 1994.Patients: 1298 patients hospitalized with an exacerbation of congestive heart failure.Measurements: Hospital costs; average daily Therapeutic Intervention Scoring System (TISS) score; and survival censored at 30, 180, and 365 days and 31 December 1994.Results: Compared with patients of generalists, patients of cardiologists were younger (mean age, 63.3 and 71.4 years; P < 0.001) and had lower Acute Physiology Scores at the time of admission (35.1 and 36.7; P < 0.001) but were more likely to have a history of ventricular arrhythmias (21.0% and 10.2%; P < 0.001). At 6 months, 201 (27%) patients of cardiologists and 149 (27%) patients of generalists had died. After adjustment for sociodemographic characteristics and severity of illness, patients of cardiologists incurred costs that were 42.9% (95% CI, 27.8% to 59.8%) higher and average daily TISS scores that were 2.83 points (CI, 1.96 to 3.68 points) higher than those of patients of generalists. Patients of cardiologists were more likely to undergo right-heart catheterization (adjusted odds ratio, 2.9 [CI, 1.7 to 4.9]) or cardiac catheterization (adjusted odds ratio, 3.9 [CI, 2.4 to 6.2]) and had higher odds for transfer to an intensive care unit and electrocardiographic monitoring. Adjusted survival did not differ significantly between groups at 30 days; however, there was a trend toward improved survival among patients of cardiologists at 1 year (adjusted relative hazard, 0.82 [CI, 0.65 to 1.04]) and at maximum follow-up (adjusted relative hazard, 0.80 [CI, 0.66 to 0.96]).Conclusions: In this observational study of patients hospitalized with congestive heart failure, cardiologist care was associated with greater costs and resource use and no difference in survival at 30 days of follow-up. Whether the trend toward better survival at longer follow-up represents differences in care or unadjusted illness severity is uncertain. [ABSTRACT FROM AUTHOR]

Context: Many individuals involved with care of the dying advocate expanding access to hospice care for persons with advanced lung, heart, or liver disease. However, to be eligible, these patients generally must have a prognosis for survival of less than 6 months.Objective: To test the ability of currently available criteria to identify a population with a survival prognosis of 6 months or less among seriously ill hospitalized patients with 1 of 3 commonly fatal chronic diseases.Design: Validation study using data from the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) phase 1 (June 1989-June 1991) and phase 2 (January 1992-January 1994), with a 6-month follow-up.Setting and Patients: Consecutive sample of 2607 seriously ill patients from 5 US medical centers who were hospitalized with chronic obstructive pulmonary disease, congestive heart failure, or end-stage liver disease, and who survived to hospital discharge.Main Outcome Measures: Descriptive and operating characteristics of 5 general and 2 disease-specific clinical criteria for identifying patients with a survival prognosis of 6 months or less, and 3 sets of combination criteria (broad, intermediate, and narrow inclusion) aimed at providing low, medium, and high thresholds for hospice eligibility based on National Hospice Organization guidelines.Results: Seventy-five percent of the sample survived more than 6 months after hospital discharge; 44% expressed a preference for palliative care. Broad inclusion criteria identified 923 patients eligible for hospice care, of whom 70% survived longer than 6 months. Intermediate inclusion criteria identified 300 patients, of whom 65% survived longer than 6 months. Narrow inclusion criteria identified 19 patients, of whom 53% survived longer than 6 months. Sensitivities and specificities of the combination criteria were 41.7% and 66.7% (broad inclusion), 16.2% and 90.1 % (intermediate inclusion), and 1.4% and 99.5% (narrow inclusion), respectively.Conclusions: These data indicate that for seriously ill hospitalized patients with advanced chronic obstructive pulmonary disease, congestive heart failure, or end-stage liver disease, recommended clinical prediction criteria are not effective in identifying a population with a survival prognosis of 6 months or less. [ABSTRACT FROM AUTHOR]

BACKGROUND: Serious illness often causes economic hardship for patients' families. However, it is not known whether this hardship is associated with a preference for the goal of care to focus on maximizing comfort instead of maximizing life expectancy or whether economic hardship might give rise to disagreement between patients and surrogates over the goal of care. METHODS: We performed a cross-sectional study of 3158 seriously ill patients (median age, 63 years; 44% women) at 5 tertiary medical centers with 1 of 9 diagnoses associated with a high risk of mortality. Two months after their index hospitalization, patients and surrogates were surveyed about patients' preferences for the primary goal of care: either care focused on extending life or care focused on maximizing comfort. Patients and surrogates were also surveyed about the financial impact of the illness on the patient's family. RESULTS: A report of economic hardship on the family as a result of the illness was associated with a preference for comfort care over life-extending care (odds ratio, 1.26; 95% confidence interval, 1.07-1.48) in an age-stratified bivariate analysis. Similarly, in a multivariable analysis controlling for patient demographics, illness severity, functional dependency, depression, anxiety, and pain, economic hardship on the family remained associated with a preference for comfort care over life-extending care (odds ratio, 1.31; 95% confidence interval, 1.10-1.57). Economic hardship on the family did not affect either the frequency or direction of patient-surrogate disagreements about the goal of care. CONCLUSIONS: In patients with serious illness, economic hardship on the family is associated with preferences for comfort care over life-extending care. However, economic hardship on the family does not appear to be a factor in patient-surrogate disagreements about the goal of care. [ABSTRACT FROM AUTHOR]

Objective: To describe the association between hospital resource utilization and physicians' knowledge of patient preferences for cardiopulmonary resuscitation (CPR) among seriously ill hospitalized adult patients.Design: Prospective cohort study.Setting: Five U.S. academic medical center, 1989-1991.Patients: A sample of 2,636 patients with self- or surrogate interviews and matching physician interviews describing patient preferences for CPR, from a cohort of 4,301 patients with life-threatening illnesses enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT).Measures: Patient, surrogate, and physician reports of preferences for resuscitation, and resource use derived from the Therapeutic Intensity Scoring System and hospital length of stay, converted into 1990 dollars.Results: Nearly one-third of the patients preferred to forego resuscitation. Of the 2,636 paired physician-patient answers, nearly one-third did not agree about preferences for resuscitation. The physicians' views of the patients' preferences and those preferences themselves were both associated with resource use. Standardized adjusted hospital resource consumption, expressed as average cost in dollars during the enrollment hospitalization, was lowest when the physician agreed with the patient preference for a do-not-resuscitate order ($20,527), and highest when the patient did not have a preference and the physician believed the patient wanted resuscitation in the case of a cardiopulmonary arrest ($34,829). Hospital resource use was intermediate when patient-physician pairs evidenced either lack of agreement or communication, or awareness of options about resuscitation.Conclusions: Both physician and patient preferences for CPR influence total hospital resource consumption. Physician misunderstanding of patient preferences to forego CPR was associated with increased use of hospital resources, and could have led to a course of care at odds with patients' expressed preferences in the event of cardiac arrest. Increasing physicians' knowledge of patient preferences, and increasing communication to help patients understand that options for medical care that include foregoing resuscitation efforts, might reduce hospital expenditures for the seriously ill. [ABSTRACT FROM AUTHOR]

Objectives: 1) to determine the rate of alcoholism among general internal medicine inpatients, 2) to assess the recognition and referral rates of these patients by their physicians, 3) to determine the effect of patient gender on physician recognition of alcoholism, and 4) to compare the observed alcoholism rates with rates reported in frequently cited studies, controlling for gender distribution.Design: Cross-sectional study, face-to-face interviews.Setting: A large, county-owned metropolitan teaching hospital.Patients/participants: Adult patients admitted to an inpatient general medical firm. From among 95 consecutive admissions, 78 patients (81%) entered the study.Intervention: The Michigan Alcoholism Screening Test (MAST) was administered to all study subjects. Chart reviews provided evidence of physician recognition and referral of patients with alcoholism. The observed rate of alcoholism was compared with rates reported in frequently cited studies after stratifying by type of service sampled and alcoholism assessment method used. Rates were then standardized for gender using the direct method.Measurements and Main Results: Twenty-two patients (28%) were found to be alcoholic by MAST criteria (scores of 5 or higher). Scores in the range indicative of alcoholism were observed more frequently among the 36 men than among the 42 women (p = 0.002) and varied by age group. Only the interaction between gender and age group was significant (p = 0.023). Sixteen of the 22 patients (73%) with alcoholism by MAST criteria were identified as alcoholic by physician evaluation. Physicians were significantly more likely to identify as alcoholic those patients with MAST scores higher than 29 and tended to more readily identify men who had alcoholism than women. Among physician-identified patients, only about one in five was referred for rehabilitation. The standardized alcoholism rate found (291/1,000) ranked about halfway between the highest and the lowest standardized rates from nine other studies of medicine inpatient services (465/1,000 and 112/1,000).Conclusions: Patient gender affected the prevalence of alcoholism and influenced its recognition by physicians. Alcoholism by MAST criteria was found in one in eight female and nearly one in two male inpatients. Physician recognition was higher for men and for more severely affected patients. An understanding of gender effects is essential to the appropriate interpretation of the results of screening tests for alcoholism and to understanding differences in reported crude rates of alcoholism among studies. Supplementing clinical impressions with the routine use of standardized methods for detecting alcoholism is recommended. [ABSTRACT FROM AUTHOR]

Much of medical practice involves the exercise of such basic cognitive tasks as estimating probabilities and synthesizing information. Scientists studying cognitive processes have identified impediments to accurate performance on these tasks. Together the impediments foster "cognitive bias." Five factors that can detract from accurate probability estimation and three that impair accurate information synthesis are discussed. Examples of all eight factors are illustrated by reference to published articles. The authors suggest ways to minimize the negative influences of these factors. [ABSTRACT FROM AUTHOR]

Introduction: Suramin is a synthetic polysulfonated naphthylurea which has been used for the treatment of African trypanosomiasis and onchocerciasis, but since the mid-1980s has received attention as a possible antiretroviral and antineoplastic agent. Objective: This clinical trial of suramin was undertaken as a phase I/II study in patients with hormone-refractory prostate cancer, with the hypothesis that the intensity of therapy with suramin could be increased significantly if measures were undertaken to maintain the plasma concentrations of the drug under 300 μg/ml. Methods: We report the clinical results of this trial, wherein patients were treated at three different targeted plasma suramin concentrations (275, 215 and 175 μg/ml) for varying periods of time (2, 4 or 8 weeks), with delivery of the drug by continuous intravenous infusion. Results: The major toxicity observed in this trial was neurologic, consisting of a motor and sensory peripheral neuropathy that resulted in both paresis and paralysis of the limbs. Nearly all of this severe (CTEP grade III, IV) neurologic toxicity was observed in the patients treated at a plasma suramin concentration of 275 μg/ml for 4 or more weeks. A single patient treated at 215 μg/ml for 8 weeks developed moderate (CTEP grade III) proximal lower extremity weakness, and no patient treated at 175 μg/ml developed this toxicity. The second most common toxicity observed was infection of the central venous catheter. The overall response rate for all of the evaluable patients was 17% (13 of 75 patients). In addition, prostate-specific antigen (PSA)-defined responses were observed in six patients receiving therapy at 175 μg/ml, but these responses were confounded by cessation of therapy with flutamide during suramin treatment. Conclusions: In summary, although plasma suramin concentrations were maintained below 300 μg/ml, neurologic toxicity nonetheless occurred with high frequency in patients treated at 275 μg/ml for 4 or more weeks. Therapy at 215 and 175 μg/ml was in general well tolerated, but central venous catheter-related infection, as well as the inconvenience and expense of continuous infusional therapy, make this method of drug delivery impractical. Only moderate antitumor activity was observed during this trial, but it is possible that both continuation of flutamide and flutamide withdrawal during suramin therapy confounded the assessment of suramin's activity in hormone-refractory prostate cancer. [ABSTRACT FROM AUTHOR]

Context: Health values (utilities or preferences for health states) are often incorporated into clinical decisions and health care policy when issues of quality vs length of life arise, but little is known about health values of the very old.Objective: To assess health values of older hospitalized patients, compare their values with those of their surrogate decision makers, investigate possible determinants of health values, and determine whether health values change over time.Design: A prospective, longitudinal, multicenter cohort study.Setting: Four academic medical centers.Participants: Four hundred fourteen hospitalized patients aged 80 years or older and their surrogate decision makers who were interviewed and understood the task.Main Outcome Measures: Time-trade-off utilities, reflecting preferences for current health relative to a shorter but healthy life.Results: On average, patients equated living 1 year in their current state of health with living 9.7 months in excellent health (mean [SD] utility, 0.81 [0.28]). Although only 126 patients (30.7%) rated their current quality of life as excellent or very good, 284 (68.6%) were willing to give up at most 1 month of 12 in exchange for excellent health (utility > or =0.92). At the other extreme, 25 (6.0%) were willing to live 2 weeks or less in excellent health rather than 1 year in their current state of health (utility < or =0.04). Patients were willing to trade significantly less time for a healthy life than their surrogates assumed they would (mean difference, 0.05; P=.007); 61 surrogates (20.3%) underestimated the patient's time-trade-off score by 0.25 (3 months of 12) or more. Patients willing to trade less time for better health were more likely to want resuscitation and other measures to extend life. Time-trade-off score correlated only modestly with quality-of-life rating (r=0.28) and inversely with depression score (r=-0.27), but there were few other clinical or demographic predictors of health values. When patients who survived were asked the time-trade-off question again at 1 year, they were willing to trade less time for better health than at baseline (mean difference, 0.04; P=.04).Conclusion: Very old hospitalized patients who could be interviewed were able, in most cases, to have their health values assessed using the time-trade-off technique. Most patients were unwilling to trade much time for excellent health, but preferences varied greatly. Because proxies and multivariable analyses cannot gauge health values of elderly hospitalized patients accurately, health values of the very old should be elicited directly from the patient. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between the use of right heart catheterization (RHC) during the first 24 hours of care in the intensive care unit (ICU) and subsequent survival, length of stay, intensity of care, and cost of care.Design: Prospective cohort study.Setting: Five US teaching hospitals between 1989 and 1994.Subjects: A total of 5735 critically ill adult patients receiving care in an ICU for 1 of 9 prespecified disease categories.Main Outcome Measures: Survival time, cost of care, intensity of care, and length of stay in the ICU and hospital, determined from the clinical record and from the National Death Index. A propensity score for RHC was constructed using multivariable logistic regression. Case-matching and multivariable regression modeling techniques were used to estimate the association of RHC with specific outcomes after adjusting for treatment selection using the propensity score. Sensitivity analysis was used to estimate the potential effect of an unidentified or missing covariate on the results.Results: By case-matching analysis, patients with RHC had an increased 30-day mortality (odds ratio, 1.24; 95% confidence interval, 1.03-1.49). The mean cost (25th, 50th, 75th percentiles) per hospital stay was $49 300 ($17 000, $30 500, $56 600) with RHC and $35 700 ($11 300, $20 600, $39 200) without RHC. Mean length of stay in the ICU was 14.8 (5, 9, 17) days with RHC and 13.0 (4, 7, 14) days without RHC. These findings were all confirmed by multivariable modeling techniques. Subgroup analysis did not reveal any patient group or site for which RHC was associated with improved outcomes. Patients with higher baseline probability of surviving 2 months had the highest relative risk of death following RHC. Sensitivity analysis suggested that a missing covariate would have to increase the risk of death 6-fold and the risk of RHC 6-fold for a true beneficial effect of RHC to be misrepresented as harmful.Conclusion: In this observational study of critically ill patients, after adjustment for treatment selection bias, RHC was associated with increased mortality and increased utilization of resources. The cause of this apparent lack of benefit is unclear. The results of this analysis should be confirmed in other observational studies. These findings justify reconsideration of a randomized controlled trial of RHC and may guide patient selection for such a study. [ABSTRACT FROM AUTHOR]

To assess the sensitivity of historical risk factors for identification for hepatitis B surface antigen (HBsAg)-positive parturients, 4399 pregnant women were consecutively screened for HBsAg. Information regarding risk for hepatitis B infection was obtained from each HBsAg-positive parturient. Twenty-three HBsAg-positive subjects were identified (5.2/1000 deliveries). The HBsAg carrier rate (18/2231, or 8.1/1000 deliveries) was significantly higher in women of black, Asian, or Hispanic origin than in the remaining ethnic groups (non-Hispanic whites plus all others, 5/2168, or 2.3/1000 deliveries) (chi square, 5.95; p = 0.016). Risk factors for identification of HBsAg-positive women were present in 10 of 22 asymptomatic subjects (sensitivity, 45%; 95% confidence interval, 24% to 68%). Much of the information required to assess one of these risk factors, previous infection, involved detailed questioning and is unlikely to be obtained in the context of conventional obstetrical care. Routine maternal HBsAg screening programs may be needed if transmission of hepatitis B from mother to infant is to be prevented. [ABSTRACT FROM AUTHOR]

Objective: To assess 1) the health values and health ratings of seriously ill hospitalized patients, their surrogate decision makers, and their physicians; 2) the determinants of health values; and 3) whether health values change over time.Design: Prospective, longitudinal, multicenter study.Setting: 5 academic medical centers.Participants: 1438 seriously ill patients with at least one of nine diseases who had a projected overall 6-month mortality rate of 50%; their surrogates; and their physicians.Measurements: Time-tradeoff utilities (reflecting preferences for a shorter but healthy life) and health ratings.Results: At study day 3, patients had a mean time-tradeoff utility of 0.73 +/- 0.32 (median [25th, 75th percentile], 0.92 [0.63, 1.0]), indicating that they equated living 1 year in their current state of health with living 8.8 months in excellent health. However, scores varied widely; 34.8% of patients were unwilling to exchange any time in their current state of health for a shorter life in excellent health (utility, 1.0), and 9.0% were willing to live 2 weeks or less in excellent health rather than 1 year in their current state of health (utility, 0.04). Health rating scores averaged 57.8 +/- 24.0 (median [25th percentile, 75th percentile], 60 [50, 75]) on a scale of 0 (death) to 100 (perfect health). The patients' mean time-tradeoff score exceeded that of their paired surrogates (n = 1041) by 0.08 (P < 0.0001). Time-tradeoff scores were related to psychosocial well-being; health ratings; desire for resuscitation and extension of life rather than relief of pain and discomfort; degree of willingness to live with constant pain; and perceived prognosis for survival and independent functioning. Scores of surviving patients increased by an average of 0.06 after 2 months (P < 0.0001) and 0.08 after 6 months (P < 0.0001).Conclusions: Health values of seriously ill patients vary widely, are higher than patients' surrogates believe, are related to few other preference and health status measures, and increase over time. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate a prognostic model that estimates survival over a 180-day period for seriously ill hospitalized adults (phase I of SUPPORT [Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments]) and to compare this model's predictions with those of an existing prognostic system and with physicians' independent estimates (SUPPORT phase II).Design: Prospective cohort study.Setting: 5 tertiary care academic centers in the United States.Participants: 4301 hospitalized adults were selected for phase I according to diagnosis and severity of illness; 4028 patients were evaluated from phase II.Measurements: A survival model was developed using the following predictor variables: diagnosis, age, number of days in the hospital before study entry, presence of cancer, neurologic function, and 11 physiologic measures recorded on day 3 after study entry. Physicians were interviewed on day 3. Patients were followed for survival for 180 days after study entry.Results: The area under the receiver-operating characteristics (ROC) curve for prediction of surviving 180 days was 0.79 in phase I, 0.78 in the phase II independent validation, and 0.78 when the acute physiology score from the APACHE (Acute Physiology, Age, Chronic Health Evaluation) III prognostic scoring system was substituted for the SUPPORT physiology score. For phase II patients, the SUPPORT model had equal discrimination and slightly improved calibration compared with physician's estimates. Combining the SUPPORT model with physician's estimates improved both predictive accuracy (ROC curve area = 0.82) and the ability to identify patients with high probabilities of survival or death.Conclusions: A limited amount of readily available clinical information can provide a foundation for long-term survival estimates that are as accurate as physicians' estimates. The best survival estimates combine an objective prognosis with a physician's clinical estimate. [ABSTRACT FROM AUTHOR]

This paper examines teachers' views of drugs education in primary schools as indicated by the findings of a survey of primary schools (including through primary schools, junior schools and infant schools) in the former County of Avon. Teachers responding to this survey wanted good in-service support, and publications that can be easily understood and used in the classroom. Teachers expressed the need for support in teaching children at Key Stage 1, that is, for children aged 5 to 7 years. Older children currently receive the bulk of attention. Respondents were divided over the need for teaching infant-school children specifically about illegal drugs. Over half felt that such children were too young. However, over 90 per cent felt that drugs education should begin before secondary school. Schools were generally optimistic about the potential impact of drugs education on young people's drug use. However they overwhelmingly stated that schools should not be seen as the sole source of drugs education for young people. [ABSTRACT FROM AUTHOR]