Restrictive Guidelines Research Articles

Tolcapone-related liver dysfunction: implications for use in Parkinson's disease therapy.

Levodopa is the cornerstone of idiopathic Parkinson's disease (PD) treatment. However, after long-term use of levodopa, a significant percentage of patients experience motor fluctuations, which worsen their quality of life. Catechol-O-methyltransferase (COMT) inhibitors reduce levodopa metabolism and enhance the respective plasma levels, resulting in improvements in symptoms and overall quality of life. Tolcapone was the first drug of this class to be marketed, but was withdrawn in the European Union due to its implication in the deaths of three PD patients due to hepatic failure. Three deaths from fulminant hepatic failure in 40000 patient-years is a number that is 10-100 times higher than the expected incidence in the general population and, according to the manufacturer's own information, the number is probably underestimated due to under-reporting of cases. In the US, tolcapone was not withdrawn, but restrictive liver enzyme monitoring measures were issued by authorities, which severely limited its use. No further deaths from hepatic failure were reported since these measures were implemented. The mechanisms by which tolcapone may induce liver toxicity are still under debate. It was thought that mitochondrial uncoupling of oxidative phosphorylation by tolcapone, and consequent impairment of energy production by hepatocytes, could be responsible for the observed effects. Some experts consider that the restrictive guidelines issued in the US regarding tolcapone use may be loosened with no consequential reductions in safety. It was suggested that ongoing clinical information about safety should be considered and periodical revisions of the restrictions made accordingly. The identification of the molecular and biochemical basis of tolcapone hepatotoxicity, when completed, should also provide important indications for the clinical use of this drug. In conclusion, appropriate monitoring of liver function can ensure adequate safety in PD patients receiving tolcapone, who can therefore benefit from the symptomatic improvements obtained with this drug.

EXAMINATION AND TREATMENT OF EARLY ANDY WARHOL HAND-COLORED LITHOGRAPHS

Nearly invisible, solvent-sensitive inks were found on several handcolored lithographs from an edition of Andy Warhol’s À la Recherche du Shoe Perdu portfolio, c. 1955. Research confirmed that the colorants were Dr. Ph. Martin’s Synchromatic Transparent Watercolors, tinctorially brilliant but highly fugitive water-based inks. Preliminary instrumental analysis (Fourier transform infrared spectroscopy, high pressure liquid chromatography) characterized the inks as mixtures of various synthetic dyes, some of them similar to ordinary food coloring. Accelerated light aging and color change calculations indicated that these inks are among the most light-sensitive media found on works of art on paper. Options for treatment of works incorporating these popular inks and suggested restrictive exhibition guidelines are presented.

Measurements of perceived coercion; methodological problems

This paper assesses the impact of a statutory change in psychiatric commitment laws on the dangerousness of involuntarily committed civil patients in one metropolitan area. More restrictive local guidelines for commitment emphasizing assaultiveness were replaced by a new state law which expanded the criteria to those whose health might deteriorate from neglect. Using an interrupted time-series analysis, we find that changes in the proportion of persons hospitalized as dangerous (or assaultive) occurred more among normally less assaultive groups such as older, white and female patients than among normally more assaultive categories of younger, black and male patients. The less assaultive groups contained an increasing proportion of dangerous patients under the period of restrictive guidelines but the proportion dropped dramatically following the implementation of the less restrictive law. Groups typified by higher rates of assaultiveness remained at a relatively high level, unaffected by changes in the statutes or time. Given the relative stability in the numbers of OTA patients committed over time, the results suggest that changes in the proportion of patients said to be dangerous may be an artifact of the way petitioners for patients and providers make use of the mental health system.

Indications for implantable cardioverter defibrillator therapy.

The implantable cardioverter defibrillator (ICD) is now an integral therapy for cardiac patient care. More than 20 years have passed since the first ICD implant. Sudden cardiac death from arrhythmia (ventricular tachycardia and fibrillation) has been significantly decreased because of the use of ICD therapy. Primary treatment trials have shown ICD therapy to be superior to drug therapy. Most of these trials compared ICD therapy with amiodarone or sotalol. Prevention trials have also been completed. Patients with nonsustained ventricular tachycardia, low left ventricular ejection fraction, and coronary artery disease were evaluated with electrophysiology studies. Patients with inducible ventricular arrhythmias were treated with ICD or drug suppression therapy. ICD therapy was superior to drug therapy for prevention of fatal arrhythmias. Ongoing trials include evaluation of ICD therapy for patients with high-risk substrates: congestive heart failure, dilated cardiomyopathy, hypertrophic cardiomyopathy, and repolarization syndromes. Factors such as medication inefficacy/side effects, transvenous ICD implantation and overwhelming mortality benefits have expanded ICD usage beyond the original restrictive guidelines.

Academic pediatric departments, government agencies, and children with special health care needs

Academic pediatric departments, government agencies, and children with special health care needs

Clinical Trials with an Adaptive Choice of Hypotheses

In a clinical trial with an adaptive interim analysis it is possible to modify not only the design, but even the hypothesis(es) of interest, in a formally correct manner. Two examples of clinical trials are described where modifications of hypotheses are based on substantial scientific reasons. Generally, it is emphasized that the danger of manipulation caused by flexible designs must be controlled by very restrictive guidelines.

Red blood cell transfusions in very and extremely low birthweight infants under restrictive transfusion guidelines: is exogenous erythropoietin necessary?

OBJECTIVETo examine the number and volume of red blood cell transfusions (RBCTs) in very and extremely low birthweight infants under restrictive red blood cell transfusion guidelines without erythropoietin administration, and...

Patenting genes: is it necessary and is it evil?

Patenting genes: is it necessary and is it evil?

Changing practices of red blood cell transfusions in infants with birth weights less than 1000 g

Objective: Extremely low birth weight (ELBW) infants frequently undergo transfusion because they are critically ill, often need artificial ventilation, and have the highest blood sampling loss in relation to their weight. During the last decade our transfusion guidelines were changed 3 times to become more restrictive. We hypothesized that these modifications substantially decreased the number of transfusions in our ELBW infants. Methods: We performed a single-center analysis of 256 infants with birth weights from 500 to 999 g who were admitted from 1989 to 1997 and included 3 study periods, each starting with newly modified transfusion guidelines in April 1989, September 1991, and January 1995. We evaluated prospectively recorded clinical data and retrospective chart analysis for transfusion-related information. Results: The median number of transfusions per infant decreased from 7 in the first period to 2 in the third period, whereas donor exposure decreased from 5 to 1 and blood volume transfused decreased from 131 to 37 mL/kg birth weight ( P < .01). The median venous hematocrit measured before transfusion decreased from 43% to 35% in infants who underwent ventilation and from 41% to 31% in spontaneously breathing infants. The median birth weight decreased from 870 to 740 g and the median gestational age from 27 to 25 completed weeks ( P < .01). The overall survival rate was 75% and did not change. The incidences of retinopathy, intraventricular hemorrhage, and patent ductus arteriosus remained unchanged. Conclusion: Over this 9-year period with increasingly restrictive transfusion guidelines, the transfusion number decreased by 71% and the donor exposure by 80% in ELBW infants without adverse clinical effects. (J Pediatr 2000;136:220-4)

Risk factors for carriage of respiratory pathogens in the nasopharynx of healthy children. Ascanius Project Collaborative Group.

To assess risk factors for nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in a large sample of healthy children. In this point prevalence survey nasopharyngeal specimens were obtained from 1723 healthy children, ages 1 to 7 years, attending day-care centers or schools in 18 Italian cities. Written questionnaires for obtaining information about the demographics and medical history of the children were completed by the parents in the presence of a pediatrician. The overall carrier rate of respiratory pathogens was 17.9% (S. pneumoniae, 3.5%; H. influenzae, 11.9%; M. catarrhalis, 4.1%). Only 5% of S. pneumoniae strains were penicillin-resistant whereas approximately 40% were erythromycin-resistant. Beta-lactamase production was found in 5.8% of H. influenzae and 88.7% of M. catarrhalis isolates. By multivariate analysis age (< or = 3 years), having older siblings, a history of prolonged full-time day-care attendance and living in a rural area significantly influenced the odds of carrying nasopharyngeal respiratory pathogens, particularly in children ages 1 to 5 years. Sex, breastfeeding, passive smoking and recent upper respiratory tract infections were not significant variables. Antibiotic treatment in the previous 3 months did not affect nasopharyngeal carriage, whereas repeated treatments with a macrolide were associated with carriage of S. pneumoniae. Our results suggest that there is a strong and long term relationship between exposure to large numbers of children in the first years of life and nasopharyngeal carriage of all respiratory pathogens. In addition antimicrobial restrictive guidelines should be tailored to local microbiologic sceneries.

Perceptions and preferences of autologous blood donors.

The public's perception of autologous blood donation and transfusion as a worthwhile alternative to allogeneic blood transfusion increased dramatically with discovery of the human immunodeficiency virus. However, new concerns are being raised about the health outcomes and cost-effectiveness of the procedure. As more restrictive guidelines for autologous blood donation evolve, opposition from patients concerned about exposure to allogeneic blood may arise. Physicians' ability to reassure patients and garner their support for more restrictive policies requires an understanding of patients' concerns. The motivations, perceptions, and preferences of patients currently participating in autologous blood donation programs were investigated in this study. Results from two questionnaire studies of 647 autologous blood donors are presented. The questionnaires assessed demographics, risk perceptions, preferences, willingness to pay, and reactions to different interventions designed to decrease patient preference for autologous blood donation. Patients expressed a strong preference for the availability of autologous blood and indicated that they would be willing to pay substantial amounts of money even if the procedure were not covered by insurance. Despite education about the low risks of complications from allogeneic transfusions, an aversion to allogeneic transfusion and a willingness to pay for autologous blood donation persisted. Patients were not reassured by information on better infectious disease testing or physician recommendation against autologous blood donation. Patients currently participating in autologous blood donor programs strongly prefer continued access to this procedure, primarily because they remain concerned about the complications of allogeneic transfusions. They may not be significantly reassured despite increasingly rigorous and costly improvements in donor and component screening.

Restrictive Guidelines and Pressure to Outperform

Restrictive guidelines and an emphasis on outperforming benchmarks in the short term may cloud the relationship between clients and managers and impair long-term investment success.

Rainfall Frequency and Nitrogen and Phosphorus Runoff from Soil Amended with Poultry Litter

Repeated land application of manure has enriched runoff N and P in some areas. Here, more restrictive manure management guidelines may be adopted. The main factors affecting N and P runoff from land receiving manure include the rate, method, and timing of application. Of these factors, least information is available on timing; thus, the effect of rainfall frequency and timing (7–35 d at 2.54 cm h−1) after poultry litter application (incorporated into surface 5 cm of soil at 10 Mg ha−1; i.e., 380 kg N and 160 kg P ha−1) on N and P concentrations in runoff was investigated for 10 Oklahoma soils. Runoff N and P concentrations decreased with 10 successive rains, starting 7 d after litter application. Although the decrease in N concentration was independent of soil type, decreases in dissolved (DP) and bioavailable P (BAP) were related to percent saturation of soil P sorption sites (r2 of 0.97 and 0.62, respectively). Increasing the time between litter application and rainfall from 1 to 35 d reduced total N from 7.54 to 2.34, ammonium-N (NH4-N) 5.53 to 0.11, DP 0.74 to 0.45, and BAP 0.99 to 0.65 mg L−1, by leaching and volatilization of N and sorption of P. Nitrate-N (NO3-N) concentrations were unaffected by rainfall frequency and timing. Runoff N and P may be reduced by avoiding litter applications during periods of high rainfall probabilities, with these reductions greater for high than low P sorbing soils.

Hybrid orders: An analysis of their likely effects on sentencing practice and on forensic psychiatric practice and services

Abstract The Reed Report on psychopathic disorder cautiously recommended the introduction of a new sentencing instrument, the ‘hybrid order’ (HO). By joining a hospital order to a prison tariff, it argued that the HO might overcome psychiatric resistance to taking psychopaths for treatment. The Home Office now proposes hybrid orders for all mentally disordered offenders, including the seriously mentally ill, on criteria of appropriate punishment and public protection. In the absence of restrictive sentencing guidelines from the Court of Appeal such orders will be widely used and will alter the relationship between psychiatry and the courts. The proposal challenges the ‘health need' basis of judicial consideration of mentally disordered offenders and replaces it with an acceptance of the punishment of the mentally ill. It is the most important challenge to confront modern British forensic psychiatry.

The effect of third-party payers on the clinical decision making of physical therapists

According to Freidson, third-party payers have eroded the political and economic authority of medicine. To what extent is this also true for alternative practitioners such as physical therapists? The effect of Medicare's restrictive guidelines on physical therapy practice in skilled nursing facilities (SNFs) is examined. SNF physical therapists in Connecticut were surveyed (response rate 99%) using a mixture of open-ended and fixed-alternative responses. Results indicate that SNF physical therapists recognize Medicare criteria and view them as important. Twenty-five to 33% of SNF therapists recommend care based on the guidelines. Younger therapists, therapists with fewer years in the field, and contract therapists are more greatly influenced by the guidelines than older, more experienced, staff therapists ( P < 0.08). Those who recommend care based on the guidelines may do so because of possible nonpayment for services already rendered, or because they fear loss of their positions. The majority of Connecticut SNF patients who qualify do receive therapy and Medicare coverage. Therapists may use their knowledge of the guidelines to secure services for their patients, or SNFs may be selecting patients that have the best chances for recovery. Like physicians, SNF physical therapists are under pressure from third-party payers to economize and rationalize, but most continue to secure services for their patients.

Liver transplantation without the use of blood products.

To examine the techniques and the outcome of liver transplantation with maximal conservation of blood products and to analyze the potential benefits or drawbacks of blood conservation and salvage techniques. Case series survey. Tertiary care, major university teaching hospital. Four patients with religious objections to blood transfusions who were selected on the basis of restrictive criteria that would lower their risk for fatal hemorrhage, including coagulopathy, a thrombosed splanchnic venous system requiring extensive reconstruction, active bleeding and associated medical complications. All patients were pretreated with erythropoietin to increase production of red blood cells. All operations were performed at the same institution, with a 36-month follow-up. Orthotopic liver transplantation that used blood salvage, plateletpheresis, and autotransfusion and the withholding of the use of human blood products with the exception of albumin. Survival and postoperative complications, with the effectiveness of erythropoietin and plateletpheresis as secondary measures. All patients are alive at 36 months after orthotopic liver transplantation. One patient, a minor (13 years of age), was transfused per a state court ruling. Erythropoietin increased the production of red blood cells as shown by a mean increase in hematocrit levels of 0.08. Platelet-pheresis allowed autologous, platelet-rich plasma to be available for use after allograft reperfusion. Three major complications were resolved or corrected without sequelae. Only one patient developed postoperative hemorrhage, which was corrected surgically. The mean charge for bloodless surgery was $174,000 for the three patients with United Network for Organ Sharing (UNOS) status 3 priority for transplantation. This result was statistically significant when these patients were compared with all the patients with UNOS status 3 priority during the same period who met the same restrictive guidelines (P < .05). Only 19 of 1009 orthotopic liver transplantations performed at our institution were similar according to the UNOS status and the fulfillment of the guidelines. The mean charge for these comparison patients was $327,000, 3.8% of which was related to transfusions. Orthotopic liver transplantation without the use of blood products is possible. Blood conservation techniques do not increase morbidity or mortality and can result in fewer transfusion-related, in-hospital charges.

Relieving Painful 'Shin Splints'.

In brief Shin splints, or more precisely, medial tibial stress syndrome (MTSS), are painful and troublesome. Despite treatment or activity modification, they often recur. Distinguishing MTSS, the most common running overuse injury, from other overuse injuries can help focus treatment, which starts conservatively. Recommending activity modification, ice massage, NSAIDs, and stretching is a good first step. Patients who don't respond to treatment may need additional diagnostic workup and more restrictive activity guidelines.

Statutory change and ‘street-level’ implementation of psychiatric commitment

This paper assesses the impact of a statutory change in psychiatric commitment laws on the dangerousness of involuntarily committed civil patients in one metropolitan area. More restrictive local guidelines for commitment emphasizing assaultiveness were replaced by a new state law which expanded the criteria to those whose health might deteriorate from neglect. Using an interrupted time-series analysis, we find that changes in the proportion of persons hospitalized as dangerous (or assaultive) occurred more among normally less assaultive groups such as older, white and female patients than among normally more assaultive categories of younger, black and male patients. The less assaultive groups contained an increasing proportion of dangerous patients under the period of restrictive guidelines but the proportion dropped dramatically following the implementation of the less restrictive law. Groups typified by higher rates of assaultiveness remained at a relatively high level, unaffected by changes in the statutes or time. Given the relative stability in the numbers of OTA patients committed over time, the results suggest that changes in the proportion of patients said to be dangerous may be an artifact of the way petitioners for patients and providers make use of the mental health system.

Whither Wages?

In July 1981 the Australian Conciliation and Arbitration Commission ended its six-year experiment with acentralised wage indexation system accompanied by restrictive guidelines. Ever since then, if not before, there hasbeen considerable concern about what might be in store for us in this area. Industrial relations professionals have beenunsettled by the sheer uncertainty of the vacuum created by the Commission's departure from the field, and economistshave been left wondering about whether new procedures, whatever and however diverse they may be, will be more orless inflationary than centralised wage indexation.

Redefining the Issues in Fetal Experimentation

THERE has been a crisis of public confidence (<i>Marriage and Family Newsletter</i>, January 1972, pp 1-8) in the medical profession generated in this country by the performance of vivisection-type experiments on live aborted fetuses¹and highly questionable therapeutic trials involving institutionalized mentally defective children.^2,3Very few investigators and a small number of studies are involved. Measures to prevent a recurrence of abuses are appropriate, but the response of the medical profession to attempts to establish guidelines has been hyperbolic, and overblown, and inconsistent with the profession's crucial responsibility to patient advocacy. The issue has never been<i>whether</i>research would be conducted but<i>how</i>it would be conducted. Research is not necessarily deterred by restrictive guidelines. It is quite possible that research as a whole would be advanced if the public were reassured that no further abuses would be tolerated (<i>News &amp; Comment</i>25:8, 1974). Much of what has