Audit of screening programme for congenital hypothyroidism in Scotland 1979-93

Accepted 30 January 1997
OBJECTIVE—To evaluate the efficiency of the screening programme for congenital hypothyroidism in Scotland and to determine the outcome in the cohort of children with positive testing for thyroid stimulating hormone (TSH).
DESIGN—Establishment of comprehensive database for all Scottish infants with high TSH, detected on Guthrie screening.
SUBJECTS—344 infants born between August 1979 and December 1993 with TSH greater than 40 mU/l on initial Guthrie, or 15-40 mU/l on repeat Guthrie.
MAIN OUTCOME MEASURES—Ages at time of: (a) Guthrie collection, (b) notification of positive result by laboratory, and (c) start of treatment; audit of late diagnosis/missed cases; categorisation of positive cases into definite and probable congenital hypothyroidism, transient TSH elevation, and uncertain status; educational status of children with definite and probable congenital hypothyroidism.
RESULTS—344 positive cases were categorised as having definite (224) and probable (11) congenital hypothyroidism, transient TSH elevation (88), and status uncertain (21). The overall incidence of definite/probable congenital hypothyroidism was 1 in 4400 live births. For the definite/probable groups median age of Guthrie collection was consistently between 6 and 7 days from 1983 onwards but for the whole cohort was later than 10 days in 10.5%. Median age of notification fell from 14days in 1980 to 11 days in 1993. Median age of starting treatment ranged between 11 and 15 days from 1983 onwards. Treatment was delayed in four cases, three due to failed or late Guthrie card submission. Of 149 children with definite/probable congenital hypothyroidism who were of school age, educational status was ascertained in 139 (93%). Only two children (1.4%) were attending special school, one of whom was known to have mild hypothyroidism. Sixteen children (11.5%) were receiving extra help in mainstream education compared with 18% of control children in the Scottish very low birth weight study.
CONCLUSION—The current screening programme is working well, but efficiency could be increased by earlier and more reliable Guthrie collection. A substantial proportion of children picked up on the screening programme have a transient rise in TSH rather than true congenital hypothyroidism. The incidence of special education and learning support in Scottish children with congenital hypothyroidism appears to be no different to that of the general population.

     

Contraindicated use of cisapride: impact of food and drug administration regulatory action

Context  Cisapride, a gastrointestinal tract promotility agent, can cause life-threatening cardiac arrhythmias in patients susceptible either because of concurrent use of medications that interfere with cisapride metabolism or prolong the QT interval or because of the presence of other diseases that predispose to such arrhythmias. In June 1998, the US Food and Drug Administration (FDA) determined that use of cisapride was contraindicated in such patients and informed practitioners through additions to the boxed warning in the label and a "Dear Health Care Professional" letter sent by the drug's manufacturer. Objective  To evaluate the impact of the FDA's 1998 regulatory action regarding contraindicated use of cisapride. Design and Setting  Analysis of data for the 1-year periods before (July 1997-June 1998) and after (July 1998-June 1999) the regulatory action from the population-based, pharmacoepidemiology research databases of 2 managed care organizations (sites A and B) and a state Medicaid program (site C). Participants  Patients with at least 180 days of prior enrollment in 1 of the 3 sites who were prescribed cisapride at least once in the period before (n = 24 840) or after (n = 22 459) regulatory action. Patients could be included in both cohorts. Main Outcome Measures  Proportion of cisapride users in each period for whom cisapride use was contraindicated by the product label, based on computerized patient medical encounter records. Results  In the year prior to regulatory action, cisapride use was contraindicated for 26%, 30%, and 60% of users in study sites A, B, and C, respectively. In the year after regulatory action, use was contraindicated for 24%, 28%, and 58% of users, a reduction in contraindicated use of approximately 2 per 100 cisapride users at each site. When the analysis was restricted to new users of cisapride after regulatory action, only minor reductions in contraindicated use were found. Conclusion  The FDA's 1998 regulatory action regarding cisapride use had no material effect on contraindicated cisapride use. More effective ways to communicate new information about drug safety are needed.      

The role of prostate-specific antigen (PSA) testing patterns in the recent prostate cancer incidence declinein the United States

Objectives: Trends in first-time and later PSA procedure rates are ascertained using longitudinal data from a population-based cohort. These trends are compared to trends in prostate cancer incidence to determine the role of PSA in the recent decline in prostate cancer incidence.Methods: Medicare data were linked with tumor registry data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. A 5 percent random sample (n=39985) of Medicare beneficiaries from the SEER areas without a previous diagnosis of prostate cancer as of January 1, 1988 was followed through 1994. Trends in first-time PSA use were distinguished from those of second or later for men without diagnosed prostate cancer.Results: Trends in the rate of first-time PSA procedures track closely with trends in prostate cancer incidence rates, increasing until 1992 and decreasing thereafter. Similar patterns were observed by race and age group. Geographic variability in the dissemination of PSA screening was observed, yet the association between testing and incidence remained. Men in the cohort had a 4.7 percent chance of being diagnosed within three months of an initial PSA test, with the percentage falling for subsequent tests.Conclusions: It is informative to distinguish first from later tests when assessing the effect of the diffusion of a test in a population. Taking this approach was useful in illuminating the role of PSA testing in a reversal of a long-term increase in prostate cancer incidence rates.     

The validity of continuous automated fluid monitoring during endometrial surgery: luxury or necessity?

Thirty-four consecutive women undergoing endometrial laser ablation, as a treatment of menorrhagia, were recruited to assess the validity of fluid absorption monitoring by a new continuous automated system (AquaSens). The same group of women also had monitoring of fluid absorption carried out by our standard technique of weighing. The intra-class correlation coefficient for the fluid deficit estimated by AquaSens compared to our standard technique of manually weighing the irrigation bags was 0.98 (95% CI 0.96–0.99). Aquasens therefore provides a valid and non-invasive method of continuously monitoring fluid deficit amongst patients undergoing operative hysteroscopy procedures, thereby reducing the risk of unexpected fluid absorption and its potentially fatal sequelae.     

Gelsolin inhibits the fibrillization of amyloid beta-protein, and also defibrillizes its preformed fibrils

Amyloid beta-protein (Abeta) is present in soluble form in the plasma and cerebrospinal fluid (CSF) of normal people and patients with Alzheimer's disease (AD). However, in AD patients, Abeta gets fibrillized as the main constituent of amyloid plaques in the brain. Soluble synthetic Abeta also forms amyloid-like fibrils when it is allowed to age. The mechanism that prevents soluble Abeta from fibrillization in biological fluids is not clear. We recently reported that gelsolin, a secretory protein, binds to Abeta, and that gelsolin/Abeta complex is present in the plasma [V.P.S. Chauhan, I. Ray, A. Chauhan, H.M. Wisniewski, Biochem. Biophys. Res. Commun. 258 (1999) 241-246.]. We now studied the effect of gelsolin on Abeta fibrillization. Congo red staining and electron microscopic examination in negative staining of aged samples of Abeta alone and Abeta incubated with gelsolin showed that gelsolin inhibits the fibrillization of synthetic Abeta 1-40 and Abeta 1-42 at gelsolin to Abeta molar ratio of 1:40. In addition, gelsolin also defibrillized the preformed fibrils of Abeta 1-40 and Abeta 1-42 in a time-dependent manner. These results suggest that gelsolin functions as an anti-amyloidogenic protein in the plasma and CSF, where it prevents Abeta from fibrillization, and helps to maintain it in the soluble form.     

Caspase inhibitors are functionally neuroprotective against oxygen glucose deprivation induced CA1 death in rat organotypic hippocampal slices

We have explored the neuroprotective efficacy of the cell penetrant caspase inhibitor, Ac-YVAD-cmk, in a hippocampal slice model of neuronal cell death induced by oxygen and glucose deprivation. Organotypic hippocampal slice cultures were prepared from 8 to 10-day-old rats and maintained for 10 to 12 days in vitro. Pre-treatment with Ac-YVAD-cmk prior to 45 min oxygen and glucose deprivation was neuroprotective as measured by propidium iodide uptake, with an EC(50) between 1 and 10 micromol/l. Ac-YVAD-cmk was also able to preserve synaptic function in the organotypic hippocampal slice cultures 24 h after oxygen and glucose deprivation. Ac-YVAD-cmk prevented the increase in histone-associated DNA fragmentation induced by oxygen and glucose deprivation. Interleukin-1beta did not reverse the protective effect of Ac-YVAD-cmk, and interleukin-1 receptor antagonist alone was not protective. These results show that caspase inhibitors are neuroprotective in a hippocampal slice culture system, using structural, biochemical and electrophysiological endpoints, and that this effect is not a result of inhibition of interleukin-1beta production.     

Quality improvement in immunization delivery following an unsuccessful immunization recall.

OBJECTIVES: Within a clinic serving disadvantaged children, 1) to evaluate a multifaceted quality improvement (QI) project to improve immunization (IZ) up-to-date (UTD) rates and 2) to assess the efficacy of IZ reminder/recall performed following QI. METHODS: A year-long QI project followed by a trial of reminder/recall. QI interventions were targeted at previously identified barriers to IZ and were designed specifically to improve the efficacy of reminder/recall. QI interventions were designed to 1) increase the use of medical record releases to document IZs received elsewhere; 2) improve the accuracy of parental contact information; and 3) reduce missed opportunities by utilizing chart prompts, provider education, and provider reminders. Following QI, we conducted a randomized trial of reminder/recall. RESULTS: UTD rates for 7-11 month olds increased from 21% before the QI project to 52% after (P <.0001); rates for 12-18 month olds increased from 16% before QI to 44% after (P <.0001); 19-25 month olds 18% before to 33% after (P <.001). After QI, an average of 61 records per month were updated with IZs received elsewhere. However, the accuracy of parental contact information worsened (29% unreachable before QI vs 44% after, P <.001) and missed opportunities did not improve (8% before vs 6% after, P = not significant [NS]). A subsequent trial of reminder/recall did not increase UTD rates, with 17% of recalled children brought UTD vs 16% of controls (P = NS). CONCLUSIONS: Clinic-based QI increased documented UTD rates in a disadvantaged patient population. However, IZ reminder/recall did not further increase UTD rates above the rates achieved by the QI process.