Abolition of prescription charges in Wales: the impact on medicines use in those who used to pay.

OBJECTIVES: patient co-payments for prescription medicines in Wales were abolished in April 2007 and there has been much speculation on the possible effects. We analysed patient-reported use of medicines before and after abolition of the prescription charge, noting changes in the number of items prescribed, number of non-prescription medicines purchased and participants not collecting all prescribed items (primary non-adherence). METHODS: a sample of community pharmacists across Wales (n = 249) issued questionnaires to customers at the point of dispensing who were not exempt from the prescription charge. A second questionnaire was delivered by post to those who returned the first questionnaire (n = 1027) and expressed a willingness to participate further. Paired t-tests were applied to responses from those completing both questionnaires (n = 593). Further analyses were carried out according to gender, age and reported levels of household income. KEY FINDINGS: there was a statistically significant (P = 0.03) rise in the number of items prescribed, and a statistically significant fall (P = 0.02) in the number of non-prescription medicines purchased. Primary non-adherence was also found to fall between pre- and post-abolition periods. Those most affected in terms of increase in number of prescribed items prescribed were the older age group (45-59 years), and those with household income of between £15600 and £36400. The most affected in the fall in number of medicines purchased were males, those in the lower age group (25-34 years) and those with a higher household income (>£36400). CONCLUSIONS: although the rise in number of items prescribed and fall in number of medicines purchased was generally anticipated, there appeared to be little or no effect for those on the lowest incomes.

Abolition of prescription copayments in Wales: an observational study on dispensing rates.

OBJECTIVE: To assess effects of abolition of prescription copayments in Wales on rates of dispensing. METHODS: General practice-level monthly dispensing data were compared before/after abolition between Wales and North East (NE) England where the charge was retained. Data for 14 medicines that had most items dispensed subject to charge before abolition were similarly compared with NE England. For those with over-the-counter substitutes, wholesale sales to pharmacies were examined. A survey examined local initiatives, which might differentially affect dispensing between the two areas. RESULTS: Total dispensing rates (items/1000 patients) increased significantly in both areas but significantly less so in Wales (difference = -19.7, P = 0.024, 95% confidence interval [CI] = -36.7 to -2.6). For the 14 selected medicines, combined dispensing rates increased significantly in both areas but significantly more in Wales (difference = 27.51, P < 0.0001, 95% CI = 23.66-31.35). There was much variation for individual drugs, but categories tended to show this same trend except for antibiotics, where rates increased in Wales but decreased in NE England. The survey revealed few local initiatives that could explain these differences. Sales of over-the-counter substitutes did not explain the changes in dispensing. CONCLUSIONS: The Welsh policy was associated with a modest increase in dispensing rates relative to NE England for the 14 medicines with the highest number of items dispensed subject to charge before abolition. Although factors besides the copayment may have influenced these observations, the smaller relative increase in total dispensing rates in Wales suggests that the overall impact of abolition was minimal.

The influence of inflation rate on the hematologic and hemodynamic effects of intermittent pneumatic calf compression for deep vein thrombosis prophylaxis.

OBJECTIVE: The study was conducted to determine whether the different inflation rates of intermittent pneumatic compression systems used in deep vein thrombosis prophylaxis influence their hematologic and hemodynamic effects. METHODS: A rapidly inflating intermittent calf compression system and a more gently inflating equivalent were applied to 20 healthy male volunteers for 2 hours each. Venous blood samples were taken for analysis of blood coagulation and fibrinolytic potential. Blood flow velocity was measured in the femoral vein with Doppler ultrasound. RESULTS: Tissue factor pathway inhibitor significantly increased after the 2 hours of compression for both pumps (78.0 to 85.0 ng/mL rapid, P = .004; 76.5 to 78.0 ng/mL gentle, P = .5), as did plasminogen activator activity (0.85 to 1.05 IU/mL rapid, P = .006; 0.85 to 1.5 IU/mL gentle, P = 0.5). Plasminogen activator inhibitor 1 activity was reduced, although only approaching significance for the gentle system (16.5 to 14.3 AU/mL, P = .06). A D-dimer test for global fibrinolysis showed significant increases for the gently inflating system (97 to 411 ng/mL P < .001) but not for the rapidly inflating system (276 to 350 ng/mL P = .9). The rapidly inflating system produced significantly higher venous peak velocities and augmentations as expected. CONCLUSIONS: Although the data confirm that both types of intermittent compression suppress procoagulant activation, rapid inflation clearly produced no extra benefit in increasing global fibrinolysis, and may be less hematologically effective.

Risk of congenital anomalies after the opening of landfill sites.

Concern that living near a particular landfill site in Wales caused increased risk of births with congenital malformations led us to examine whether residents living close to 24 landfill sites in Wales experienced increased rates of congenital anomalies after the landfills opened compared with before they opened. We carried out a small-area study in which expected rates of congenital anomalies in births to mothers living within 2 km of the sites, before and after opening of the sites, were estimated from a logistic regression model fitted to all births in residents living at least 4 km away from these sites and hence not likely to be subject to contamination from a landfill, adjusting for hospital catchment area, year of birth, sex, maternal age, and socioeconomic deprivation score. We investigated all births from 1983 through 1997 with at least one recorded congenital anomaly [International Classification of Diseases, Ninth Revision (ICD-9), codes 7400-7599; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), codes Q000-Q999]. The ratio of the observed to expected rates of congenital anomalies before landfills opened was 0.87 [95% confidence interval (CI), 0.75-1.00], and this increased to 1.21 (95% CI, 1.04-1.40) after opening, giving a standardized risk ratio of 1.39 (95% CI, 1.12-1.72). Enhanced congenital malformation surveillance data collected from 1998 through 2000 showed a standardized risk ratio of 1.04 (95% CI, 0.88-1.21). Causal inferences are difficult because of possible biases from incomplete case ascertainment, lack of data on individual-level exposures, and other socioeconomic and lifestyle factors that may confound a relationship with area of residence. However, the increase in risk after the sites opened requires continued enhanced surveillance of congenital anomalies, and site-specific chemical exposure studies. Key words: congenital malformations, epidemiology, landfill, small-area health statistics.

Diet and colorectal cancer: an investigation of the lectin/galactose hypothesis.

BACKGROUND & AIMS: Mucosal expression of terminal unsubstituted galactose is increased in colon cancer and precancer and allows interaction with mitogenic galactose-binding lectins of dietary or microbial origin. This study tests the hypothesis that galactose, which is variably plentiful in fruit and vegetable but not cereal fibers, might prevent cancer by binding and inhibiting such lectins. METHODS: Colorectal cancer cases (512) and controls (512) were matched for age, sex, primary care practitioner, and postal code. A 160-item food-frequency questionnaire was used to estimate their usual pre-illness (6 months previous) diet, aspirin intake, and exercise. RESULTS: Neither cereal fiber nor fruit and vegetable fiber were protective when assessed by univariate analysis, whereas dietary fiber galactose content showed a dose-related protective effect (odds ratio [OR] highest quartile/lowest quartile, 0.67; confidence interval [CI], 0.47-0.95) that remained protective when adjusted for energy, red meat, alcohol, calcium, protein and fat intake, regular aspirin usage, and exercise. Intake of nonlegume green vegetables, assessed because of the high lectin content of legumes, was also protective (OR, 0.54; CI, 0.35-0.81), but this was not independent of galactose. Protective effects of exercise and regular daily aspirin consumption and harmful effects of high energy consumption and high red meat intake were confirmed. CONCLUSIONS: The protective effect of fruit and vegetable fibers may be related to their galactose content. This provides further evidence that the association between diet and colon cancer is mediated via specific food components and may explain the discrepant results of studies addressing the protective effects of fiber.

The LionHeart LVD-2000: a completely implanted left ventricular assist device for chronic circulatory support.

Management of patients with end-stage cardiac disease remains a vexing problem. Limitations in medical management and a fixed supply of donor organs for cardiac transplant have a continued impact on this growing population of patients. Mechanical circulatory support has proved very successful as a means of bridging patients to cardiac transplant when all medical options have been exhausted. The development of a chronic system of circulatory support has been underway at the Pennsylvania State University for nearly 30 years. These efforts have been recently merged with the industrial partnership with Arrow International toward the development of the LionHeart LVD-2000 (Arrow International, Reading, PA) completely implanted left ventricular support system. We present an overview of the system, details of implantation, a review of preclinical studies, and a synopsis of the first European implants. Early results have demonstrated the system to be safe, effective, and reliable. Transcutaneous energy transmission and the compliance chamber have been validated.

ncl-1 is required for the regulation of cell size and ribosomal RNA synthesis in Caenorhabditis elegans.

Regulation of ribosome synthesis is an essential aspect of growth control. Thus far, little is known about the factors that control and coordinate these processes. We show here that the Caenorhabditis elegans gene ncl-1 encodes a zinc finger protein and may be a repressor of RNA polymerase I and III transcription and an inhibitor of cell growth. Loss of function mutations in ncl-1, previously shown to result in enlarged nucleoli, result in increased rates of rRNA and 5S RNA transcription and enlarged cells. Furthermore, ncl-1 adult worms are larger, have more protein, and have twice as much rRNA as wild-type worms. Localization studies show that the level of NCL-1 protein is independently regulated in different cells of the embryo. In wild-type embryos, cells with the largest nucleoli have the lowest level of NCL-1 protein. Based on these results we propose that ncl-1 is a repressor of ribosome synthesis and cell growth.

Structure and function of the small subunit of TFIIF (RAP30) from Drosophila melanogaster.

To study the mechanism of basal transcription by RNA polymerase II, a cDNA encoding the Drosophila homologue of the small subunit of TFIIF (also referred to as TFIIF30, RAP30, factor 5b, and gamma) was isolated. The Drosophila TFIIF30 gene is located at region 86C on the right arm of the third chromosome. The protein encoded by the cDNA, termed dTFIIF30, was synthesized in Escherichia coli and purified to greater than 95% homogeneity. In reconstituted transcription reactions with purified basal factors, the specific activity of dTFIIF30 was identical to that of its human homologue. Moreover, a carboxyl-terminal fragment, designated dF30(119-276), which contains the carboxyl-terminal 158 amino acid residues of dTFIIF30, was found to possess approximately 50% of the transcriptional activity as full-length dTFIIF30. The interaction of dTFIIF30 with the large subunit of TFIIF (also referred to as TFIIF74, RAP74, factor 5a, and beta) was investigated by glycerol gradient sedimentation analyses. In these experiments, dTFIIF30, but not dF30(119-276), assembled into a stable heteromeric complex with TFIIF74. These results, combined with those of previous work on TFIIF, support a model for TFIIF30 function in which the carboxylterminal region constitutes a functional domain that can interact with RNA polymerase II to mediate basal transcription, whereas the amino terminus comprises a domain that interacts with TFIIF74.

Illness with fatalities in premature infants: association with an intravenous vitamin E preparation, E-Ferol.

Three clusters of an unusual syndrome in premature infants were investigated in three intensive care nurseries in 1984. A retrospective cohort study of 68 infants weighing less than or equal to 1,250 g at birth and surviving at least 72 hours revealed that in 13 infants ascites developed and in four at least two of the following abnormal laboratory values were found within a seven-day period: serum direct bilirubin greater than or equal to 2 mg/dL, blood urea nitrogen greater than or equal to 40 mg/dL or serum creatinine greater than or equal to 2 mg/dL, and platelet count less than or equal to 60,000/microL. All cases occurred after the introduction and use of intravenous E-Ferol, a vitamin E preparation that was new on the market when the clusters were reported. All 17 case infants but only 23 of 51 (45%) noncase infants received E-Ferol (P less than .0001). Case and noncase infants were similar with respect to other complications and to receipt of medications and parenteral nutrition. A dose-response relationship was found; cases occurred in infants receiving E-Ferol dosages of greater than 20 U/kg/d. Case infants who had higher daily doses of E-Ferol had a shorter latency. No new cases were reported after use of E-Ferol was stopped. Results of these investigations led to a nationwide recall of intravenous E-Ferol.

Vasculopathic hepatotoxicity associated with E-Ferol syndrome in low-birth-weight infants.

A fatal syndrome characterized by progressive clinical deterioration with unexplained thrombocytopenia, renal dysfunction, cholestasis, and ascites developed in certain infants throughout the United States who had received E-Ferol, an intravenous vitamin E supplement. We reviewed the clinical course of all 36 infants from one (index) nursery who had received E-Ferol, which contains 25 units per milliliter of dl-alpha-tocopheryl acetate solubilized with 9% polysorbate 80 and 1% polysorbate 20. The syndrome was recognized in eight of the 36 infants; affected infants had a lower birth weight (less than 1,200 g) and had received a higher total dose of E-Ferol for longer periods than the unaffected cases. We reviewed autopsy-derived tissue from 20 infants (six from the index nursery and 14 from three other collaborating nurseries) who had received the intravenous vitamin E preparation in a reported dose of 25 to 137 units/kg/day for six to 45 days between October 1983 and March 1984. The hepatic histology in the affected cases indicated a progressive injury characterized initially by Kupffer cell exfoliation, central lobular accumulation of cellular debris, and centrally accentuated panlobular congestion. Prolonged exposure to E-Ferol was associated with progressive intralobular cholestasis, inflammation of hepatic venules, and extensive sinusoidal veno-occlusion by fibrosis. We propose that vasculocentric hepatotoxicity is the basis for the observed clinical syndrome that represents the cumulative effect of one or more of the constituents of E-Ferol.

Primary shunt hyperbilirubinemia with secondary iron overload: a case report.

A patient with familial primary shunt hyperbilirubinemia is described. Splenomegaly, arthritis, and iron overload were striking features of the illness.

Toy safety in hospitals--or beware of parents bearing gifts.

Toys are an indispensable component of play therapy for hospitalized children. They can also be dangerous and may result in catastrophic accidents. Extreme care should be exercised in the purchase of "safe toys" for all infants and children in and out of the hospital. The guidelines of the Bureau of Product Safety of the Federal Drug Administration (FDA) dealing with toy safely can be very helpful for child card professionals as well as parents who purchase toys. An explanation of the additional environmental hazards of toys in hospital settings should be an important part of the total in-service training of all personnel who care for infants and children in hospitals. In addition, it might be well for the Division of Product Safety of the FDA to consider criteria for toy safety in hospitals as a separate category in future Bulletins dealing with this problem.