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People with learning disabilities in 'out-of-area' residential placements: 2. Reasons for and effects of placement.

BACKGROUND: Official guidance on out-of-area placements creates incentives that could lead to people being placed against their own best interests, with negative consequences for them and for the 'receiving' authorities. METHOD: Information was collected for 30 people through interviews with them, their families, home managers and care managers. Interviews concerned resident needs, reasons for placement, the homes, care management arrangements, resident quality of life and social inclusion. Information on care standards was abstracted from official records. RESULTS: The main reasons for out-of-area placement were insufficient local services of acceptable quality, financial incentives and loss of family contact through prior institutionalization. The effects varied, with the most disabled people experiencing worst outcomes. Some aspects were worse than comparison studies (choice, community involvement, number of homes meeting all the national minimum standards), some were the same (participation, family visiting and other contact), and one was better (visits to families). Variation was also evident in the involvement of social services staff from the placing authority and in ease of access to local healthcare resources. CONCLUSIONS: Social services and health authorities should develop services locally that can support people with the full range of individual needs. Perverse incentives should be removed, perhaps by increasing the application of direct payments and personalized budgets.

Adolescent↗

Genetic recombination and the cell cycle: what we have learned from chromosome dimers.

Genetic recombination is central to DNA metabolism. It promotes sequence diversity and maintains genome integrity in all organisms. However, it can have perverse effects and profoundly influence the cell cycle. In bacteria harbouring circular chromosomes, recombination frequently has an unwanted outcome, the formation of chromosome dimers. Dimers form by homologous recombination between sister chromosomes and are eventually resolved by the action of two site-specific recombinases, XerC and XerD, at their target site, dif, located in the replication terminus of the chromosome. Studies of the Xer system and of the modalities of dimer formation and resolution have yielded important knowledge on how both homologous and site-specific recombination are controlled and integrated in the cell cycle. Here, we briefly review these advances and highlight the important questions they raise.

Bacteria↗

Differential effects of new-generation H1-receptor antagonists in pruritic dermatoses.

In search of an improved treatment of pruritic dermatoses, we have studied azelastine, a novel H1-receptor antagonist, during a 2-week treatment period, using a double-blind, placebo-controlled design. The potent H1-antagonist cetirizine was used for comparison. Symptoms were recorded daily by the patients on a diary card, using a 4-point scale. The same parameters and adverse events were evaluated at weekly intervals, and global improvement was evaluated at the end of treatment. In all 230 evaluable patients with moderate to severe itching, azelastine caused an overall significant improvement in comparison to placebo (P = 0.02), with significance also for pruritus (P = 0.01 after 1 week and P = 0.02 after 2 weeks). Both drugs reduced itching more effectively in urticaria than in atopic eczema. Azelastine was superior to cetirizine in reducing pruritus, whereas cetirizine caused a more marked reduction of whealing. Both drugs rarely caused fatigue and dry mouth, but taste perversion occurred only in azelastine-treated patients (9.7%) and headaches only with cetirizine (10.4%). Therefore, the two H1-blockers exert differential effects on pruritus verses whealing and a distinctive adverse events pattern. The data also underline the low efficacy of antihistamines in atopic eczema, compared to urticaria.

Adolescent↗

Azelastine eye-drops in seasonal allergic conjunctivitis or rhinoconjunctivitis. A double-blind, randomized, placebo-controlled study.

This study was carried out to assess the efficacy of 0.025% and 0.05% azelastine eye-drops in patients with seasonal allergic conjunctivitis of > or = 1 year's duration. A total of 151 patients received 0.025% or 0.05% azelastine eye-drops or placebo b.i.d. for 14 days according to a double-blind, randomized, placebo-controlled, parallel-dosing design; 129 patients completed the study as planned. The three target symptoms, scored on 4-point scales, were itching, lacrimation, and redness of the eyes; responders were patients whose symptom sum score decreased by > or = 3 from a baseline score of > or = 6 by day 3. Mean scores of these and five other symptoms were recorded also on days 7 and 14, and patients kept daily diaries of the three main symptoms and swollen eyelids. Responder rates were 73% for 0.025% (P=0.115 vs placebo) and 82% for 0.05% azelastine eye-drops (P=0.011 vs placebo) and 56% for placebo. The time courses of the mean (investigators' and patients') scores for the three main symptoms reflected the dose-dependent effect of azelastine eye-drops. One patient each from the two azelastine groups and three from the placebo group withdrew because of inefficacy. Adverse drug reactions were reported by 14 and 24 patients receiving 0.025% and 0.05% azelastine eye-drops, respectively, and by eight placebo patients. These reactions were mainly slight application site reactions and taste perversion (bitter or unpleasant taste). Azelastine eye-drops are effective and well tolerated at a dose of 0.05% for the treatment of seasonal allergic conjunctivitis.

Adolescent↗

Learning to use the Internet as a study tool: a review of available resources and exploration of students' priorities.

BACKGROUND: The Internet is a valuable information tool, but users often struggle to locate good quality information from within the vast amount of information available. OBJECTIVE: The aim of the study was to identify the online information resources available to assist students develop Internet searching skills, and to explore the students' priorities in online guides. METHODS: A qualitative approach was adopted with two phases. The first was a structured search of available online study skills resources. The second comprised 10 group interviews with a total of 60 students at all stages of five undergraduate health and social care related courses at a UK university. RESULTS: The study found that there were good online guides available, but that, perversely, the better guides tended to require the best searching skills to locate them. A few students were enthusiastic about using online support, however the majority felt that if they had the skills to locate such resources they wouldn't use a study guide to improve these skills, and if they did not have the skills they would not think of using an online guide to develop them. CONCLUSIONS: Students wanted assistance when they had problems or questions, rather than sites that offered structured learning experiences. Personal support rather than virtual support was also considered to be most important to the students in this study.

Attitude↗

Tackling health inequalities in the United Kingdom: the progress and pitfalls of policy.

GOAL: Assess the progress and pitfalls of current United Kingdom (U.K.) policies to reduce health inequalities. OBJECTIVES: (1) Describe the context enabling health inequalities to get onto the policy agenda in the United Kingdom. (2) Categorize and assess selected current U.K. policies that may affect health inequalities. (3) Apply the "policy windows" model to understand the issues faced in formulating and implementing such policies. (4) Examine the emerging policy challenges in the U.K. and elsewhere. DATA SOURCES: Official documents, secondary analyses, and interviews with policymakers. STUDY DESIGN: Qualitative, policy analysis. DATA COLLECTION: 2001-2002. The methods were divided into two stages. The first identified policies which were connected with individual inquiry recommendations. The second involved case-studies of three policies areas which were thought to be crucial in tackling health inequalities. Both stages involved interviews with policymakers and documentary analysis. PRINCIPAL FINDINGS: (1) The current U.K. government stated a commitment to reducing health inequalities. (2) The government has begun to implement policies that address the wider determinants. (3) Some progress is evident but many indicators remain stubborn. (4) Difficulties remain in terms of coordinating policies across government and measuring progress. (5) The "policy windows" model explains the limited extent of progress and highlights current and possible future pitfalls. (6) The U.K.'s experience has lessons for other governments involved in tackling health inequalities. CONCLUSIONS: Health inequalities are on the agenda of U.K. government policy and steps have been made to address them. There are some signs of progress but much remains to be done including overcoming some of the perverse incentives at the national level, improving joint working, ensuring appropriate measures of performance/progress, and improving monitoring arrangements. A conceptual policy model aids understanding and points to ways of sustaining and extending the recent progress and overcoming pitfalls.

Health Plan Implementation↗

Long-term avifaunal impoverishment in an isolated tropical woodlot.

Long-term (> 50 years) extinction patterns and processes in isolated tropical forest patches are poorly understood. Considering that forest fragments are rapidly becoming the common feature of most tropical landscapes, data on the long-term conservation value of such fragments are urgently needed. We report on avifaunal turnover in a tropical woodlot (Bogor Botanical Gardens; 86 ha; 54% native and 46% introduced plants; mean 83,649 visitors/month) that has been surveyed several times before and after its isolation in 1936. By 2004 the original avifaunal richness of this woodlot declined by 59% (97 to 40 species) and its forest-dependent avifauna declined by 60% (30 to 12 species). Large-bodied birds were particularly prone to extinction before 1987, but following this time none of the species traits we studied could be considered predictive of extinction proneness. All seven forest-dependent bird species that attempted to colonize this woodlot by 1987 perished thereafter. Our results show that area reduction, isolation, intense human use, and perverse management (e.g., understory removal) of this patch have probably negatively affected the long-term sustainability of its forest avifauna.

Animals↗

Seven-day triple therapy with lansoprazole, clarithromycin, and metronidazole for the cure of Helicobacter pylori infection: a short report.

BACKGROUND: To refine our understanding of anti-Helicobacter pylori treatment regimens further, we evaluated the efficacy and safety of lansoprazole given in combination with clarithromycin and metronidazole for 7 days in an open-label, multicenter study. MATERIALS AND METHODS: H. pylori-positive patients self-administered lansoprazole, 30 mg; clarithromycin, 500 mg; and metronidazole, 500 mg bid for 7 days. Patients were assessed at pretreatment, at which time the presence of H. pylori was documented by rapid urease test or histology and culture, following study drug administration (week 1) for a brief evaluation only, and at least 4 weeks posttreatment (week 5), including endoscopy with collection of biopsy specimens for culture and histology testing. RESULTS: Of the 60 patients enrolled in the study, 59 had confirmed H. pylori infection, and 51 were included in an intent-to-treat analysis of efficacy. Primary metronidazole and clarithromycin resistance were observed in 84% and 8% of study patients, respectively. One month after the end of therapy, H. pylori infection was cured in 40 of 51 patients (78%); 95% confidence interval, (65%-89%). The triple-therapy regimen was well-tolerated, with only 2 patients (4%) requiring premature withdrawal from the study due to treatment-related adverse events. Taste perversion (15.0%) and diarrhea (11.7%) were the most frequently reported adverse events possibly or probably related to study medication during the treatment period. CONCLUSION: Despite a high prevalence of metronidazole resistance, a 1-week, triple-drug combination of lansoprazole, clarithromycin, and metronidazole is effective treatment for and well-tolerated by patients with H. pylori infection.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Topiramate in migraine prevention.

The efficacy of topiramate in migraine prevention (prophylaxis) was established in two multicenter, randomized, double-blind, placebo-controlled, pivotal trials. Topiramate has received regulatory approval for use in adults for migraine prophylaxis (prevention) in the US and numerous other countries, including France, Ireland, Switzerland, Brazil, Taiwan, Spain, and Australia. Treatment with 100 or 200 mg per day of topiramate was associated with significant reductions in the frequency of migraine headaches, number of migraine days, and use of acute medications. No increase in efficacy was observed between 100 and 200 mg per day of topiramate. Based on efficacy and tolerability, 100 mg per day of topiramate should be the initial target dose for most patients. The most common adverse events were paresthesia, fatigue, decreased appetite, nausea, diarrhea, weight decrease, and taste perversion. Topiramate is a first-line migraine preventive drug and should especially be considered as a preferred treatment for all patients who are concerned about gaining weight, who are currently overweight, or who have coexisting epilepsy.

Adolescent↗

Is managed care good or bad for geriatric medicine?

This article uses clinical vignettes to examine the simultaneous dangers and opportunities that managed care brings to geriatric medicine. While the complex multifactorial syndromes prevalent in older adults might at first glance seem poorly handled under capitation, we argue that the incentives provided under existing delivery systems can be equally perverse. These improper incentives have arisen from (1) the fee-for-service payment mechanism itself, which has spawned a subspecialty culture ill-equipped to deal with the primary care needs of older adults and (2) the fragmentation of funding sources for geriatric care into two major payers (Medicare and Medicaid), encouraging providers to focus on cost shifting rather than the logical integration of services. The result has been a delivery system that provides little impetus to maximize functional status, the central goal of modern geriatric medicine. Because physicians may assume financial risk under global capitation, and because the cost of caring for a frail older adult is inversely related to functional status, managed care offers the potential to align the goals of cost containment with the goals of modern geriatric medicine. Physicians should have a substantive voice in the design and implementation of these systems.

Activities of Daily Living↗

Understanding the rapist's mind.

TOPIC: The motivations and psychology of the rapist. PURPOSE: To provide a framework of sexual perversions so that the motives and psychology of rapists can be better understood. SOURCE: Analytic literature. CONCLUSION: Unconscious motives leading to rape appear related to issues of control, power, and dominance.

Conflict, Psychological↗

Comparative performance data for critical access hospitals.

CONTEXT: Among small rural hospitals, there is a growing recognition of the need to measure and report on the use of resources and the safety and quality of the services provided. Dashboards, clinical value compasses, and balanced scorecards are approaches to performance measurement that have been adopted by many health care organizations. However, there exists very little comparative performance data specific for critical access hospitals. PURPOSE: To identify how comparative performance data for critical access hospitals (CPD-CAH) might facilitate performance and quality improvement, to assess the potential benefits and drawbacks of such data, and to identify some of the critical issues in the development and implementation of CPD-CAH. METHODS: Assessment of discussions by participants at a rural hospital performance improvement summit and authors' analyses. FINDINGS: CPD-CAH potentially could improve quality of care and patient outcomes, provide comparative data and benchmarks, inform policy development, facilitate collaboration, and enhance community relations. However, CPD-CAH could also impose an unaffordable cost, produce poor information, require complex coordination, induce a negative public reaction, and result in perverse hospital behavior. Development and implementation of CPD-CAH would require including stakeholders' assessment of its desirability and feasibility, setting objectives, establishing guiding principles, developing a method, collecting and analyzing data, and disseminating results. CONCLUSIONS: CPD-CAH could significantly advance CAH performance and quality improvement. However, development and implementation would be a complicated exercise requiring academic expertise and practitioner consultation. The potential value of CPD-CAH should be carefully weighed against its potential cost.

Benchmarking↗

Race, money and medicines.

Taking notice of race is both risky and inevitable, in medicine no less than in other endeavors. On the one hand, race can be a useful stand-in for unstudied genetic and environmental factors that yield differences in disease expression and therapeutic response. Attention to race can make a therapeutic difference, to the point of saving lives. On the other hand, racial distinctions have social meanings that are often pejorative or worse, especially when these distinctions are cast as culturally or biologically fixed. I argue in this essay that we should start with a presumption against racial categories in medicine, but permit their use when it might prolong lives or meaningfully improve health. Use of racial categories should be understood as an interim step; follow-up inquiry into the factors that underlie race-correlated clinical differences is important both to improve the efficacy of clinical care and to prevent race in itself from being misunderstood as a biological determinant. If we pursue such inquiry with vigor, the pernicious effects of racial categories on public understanding can be managed. But perverse market and regulatory incentives create the danger that use of race will be "locked-in," once drugs or other therapies are approved. These incentives should be revisited.

Biomedical Research↗

The devil's choice: re-thinking law, ethics, and symptom relief in palliative care.

Health professionals do not always have the luxury of making "right" choices. This article introduces the "devil's choice" as a metaphor to describe medical choices that arise in circumstances where all the available options are both unwanted and perverse. Using the devil's choice, the paper criticizes the principle of double effect and provides a re-interpretation of the conventional legal and ethical account of symptom relief in palliative care.

Analgesics, Opioid↗

Care of the aged: old problems in need of new solutions.

Long-term care for the aged in the United States is overly dependent upon the nursing home. This hospital-like model for long-term care is particularly inappropriate since it imposes a medical solution on a variety of social problems. An adequate long-term care program requires a range of resources in the community as well as in institutions; sheltered housing options seem a desirable alternative to the nursing home. To ensure the quality of nursing home care, the present focus on setting standards for care activities should be abandoned in favor of a focus on care outcomes (physical, mental, and social). In an effort to change our present perverse incentives in the nursing home industry, the proposal is made that nursing homes be reimbursed according to the degree to which patient outcomes meet predicted outcomes.

Aged↗

Prophylactic vaccines, risk behavior change, and the probability of eradicating HIV in San Francisco.

Theory is linked with data to assess the probability of eradicating human immunodeficiency virus (HIV) in San Francisco through the use of prophylactic vaccines. The necessary vaccine efficacy levels and population coverage levels for eradication are quantified. The likely impact of risk behavior changes on vaccination campaigns is assessed. The results show it is unlikely that vaccines will be able to eradicate HIV in San Francisco unless they are combined with considerable reductions in risk behaviors. Furthermore, if risk behavior increases as the result of a vaccination campaign, then vaccination could result in a perverse outcome by increasing the severity of the epidemic.

AIDS Vaccines↗

Efficacy and safety of a 10-day course of 400 or 600 milligrams of grepafloxacin once daily for treatment of acute bacterial exacerbations of chronic bronchitis: comparison with a 10-day course of 500 milligrams of ciprofloxacin twice daily.

A randomized, prospective, double-blind, double-dummy, multicenter study investigated the efficacy and safety of 10 days of oral therapy with grepafloxacin at 400 mg once daily, grepafloxacin at 600 mg once daily, or ciprofloxacin at 500 mg twice daily in 624 patients with acute bacterial exacerbations of chronic bronchitis. At the end of treatment, clinical success (cure or improvement) was achieved for 93% (140 of 151), 88% (137 of 156), and 91% (145 of 160) of patients in the groups receiving grepafloxacin at 400 mg, grepafloxacin at 600 mg, and ciprofloxacin, respectively (clinically evaluable population). At follow-up (14 to 28 days posttreatment), the clinical success rates were 87% (124 of 143), 81% (122 of 151), and 80% (123 of 154) in the groups receiving grepafloxacin at 400 mg and 600 mg and ciprofloxacin, respectively. A total of 379 pathogens were isolated from 290 patients, with the most common isolates being Moraxella catarrhalis (21%), Staphylococcus aureus (20%), Haemophilus influenzae (18%), and Streptococcus pneumoniae (7%). For the evaluable population, successful bacteriologic response was obtained at the end of treatment for 96% (92 of 96), 98% (87 of 89), and 92% (82 of 90) of patients receiving grepafloxacin at 400 mg, grepafloxacin at 600 mg, and ciprofloxacin, respectively, and was maintained in 86% (82 of 95), 88% (78 of 89), and 82% (69 of 84) of patients, respectively, at follow-up. All pretreatment S. pneumoniae isolates were susceptible to grepafloxacin, but two strains were resistant to ciprofloxacin. All treatments were well tolerated, with the most frequently reported drug-related adverse events being nausea, taste perversion, and headache. All drug-related adverse events in the grepafloxacin groups were mild or moderate in severity. This study demonstrates that 10-day courses of grepafloxacin given at 400 or 600 mg once daily were as effective, clinically and bacteriologically, as ciprofloxacin given at 500 mg twice daily for the treatment of acute bacterial exacerbations of chronic bronchitis.

Acute Disease↗

Safety and pharmacokinetics of single doses of (+)-calanolide a, a novel, naturally occurring nonnucleoside reverse transcriptase inhibitor, in healthy, human immunodeficiency virus-negative human subjects.

(+)-Calanolide A is a novel, naturally occurring, nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase first isolated from a tropical tree (Calophyllum lanigerum) in the Malaysian rain forest. Previous studies have demonstrated that (+)-calanolide A has specific activity against the reverse transcriptase of HIV-1 and a favorable safety profile in animals. In addition, (+)-calanolide A exhibits a unique HIV-1 resistance profile in vitro. The safety and pharmacokinetics of (+)-calanolide A was examined in four successive single-dose cohorts (200, 400, 600, and 800 mg) in healthy, HIV-negative volunteers. In this initial phase I study, the toxicity of (+)-calanolide A was minimal in the 47 subjects treated. Dizziness, taste perversion, headache, eructation, and nausea were the most frequently reported adverse events. These events were not all judged to be related to study medication nor were they dose related. While 51% of subjects reported mild and transient dizziness, in many cases this appeared to be temporally related to phlebotomy. Calculation of the terminal-phase half-life (t(1/2)) was precluded by intrasubject variability in the 200-, 400-, and 600-mg dose cohorts but was approximately 20 h for the 800-mg dose group. (+)-Calanolide A was rapidly absorbed following administration, with time to maximum concentration of drug in plasma (T(max)) values occurring between 2.4 and 5.2 h postdosing depending on the dose. Plasma levels of (+)-calanolide A at all dosing levels were quite variable; however, both the mean concentration in plasma (C(max)), and the area under the plasma concentration-time curve increased proportionately in relation to the dose. Although raw plasma drug levels were higher in women than in men, when doses were normalized for body mass, the pharmacokinetic profiles were virtually identical with those observed for males. In general, levels of (+)-calanolide A in human plasma were higher than would have been predicted from animal studies, yet the safety profile remained benign. In conclusion, this study demonstrated the safety and favorable pharmacokinetic profile of single doses of (+)-calanolide A in healthy, HIV-negative individuals.

Adolescent↗