Investigating the efficiency of fitting Coxian phase-type distributions to health care data

Coxian phase-type distributions are becoming a popular means of representing survival times within a health care environment. They are favoured as they show a distribution as a system of phases and can allow for an easy visual representation of the rate of flow of patients through a system. Difficulties arise, however, in determining the parameter estimates of the Coxian phase-type distribution. This paper examines ways of making the fitting of the Coxian phase-type distribution less cumbersome by outlining different software packages and algorithms available to perform the fit and assessing their capabilities through a number of performance measures. The performance measures rate each of the methods and help in identifying the more efficient. Conclusions drawn from these performance measures suggest SAS to be the most robust package. It has a high rate of convergence in each of the four example model fits considered, short computational times, detailed output, convergence criteria options, along with a succinct ability to switch between different algorithms.

Modelling the cycling of persistent organic pollutants (POPs) in the North Sea system: Fluxes, loading, seasonality, trends

The fate and cycling of two selected POPs is investigated for the North Sea system with an improved version of a fate and transport ocean model (FANTOM). The model uses atmospheric data from the EMEP MSC East POP model (Gusev et al., 2009), giving reasonable concentrations and seasonal distributions for the entire region, as opposed to the three observation stations that Ilyina et al. (2006) were limited to. Other model improvements include changes in the calculation of POP exchange between the water column and sediment.

We chose to simulate the fate of two POPs with very different properties, ?-HCH and PCB 153. Since the fate and cycling of POPs are strongly affected by hydrodynamic processes, a high resolution version of the Hamburg Shelf Ocean Model (HAMSOM) was developed and utilised. Simulations were made for the period 1996–2005. Both models were validated by comparing results with available data, which showed that the simulations were of very satisfactory quality.

Model results show that the North Sea is a net sink for ?-HCH and a net source to the atmosphere of PCB 153. Total masses of ?-HCH and PCB 153 in 2005 are reduced to 30% and 50%, respectively, of 1996 values.

Storms resuspending bottom sediments into the water column mobilise POPs into the atmosphere and have the potential to deliver substantial loads of these POPs into Europe.

Trends in childhood type 1 diabetes incidence in Europe during 1989-2008: evidence of non-uniformity over time in rates of increase

AIMS/HYPOTHESIS:

The aim of the study was to describe 20-year incidence trends for childhood type 1 diabetes in 23 EURODIAB centres and compare rates of increase in the first (1989-1998) and second (1999-2008) halves of the period.

METHODS:

All registers operate in geographically defined regions and are based on a clinical diagnosis. Completeness of registration is assessed by capture-recapture methodology. Twenty-three centres in 19 countries registered 49,969 new cases of type 1 diabetes in individuals diagnosed before their 15th birthday during the period studied.

RESULTS:

Ascertainment exceeded 90% in most registers. During the 20-year period, all but one register showed statistically significant changes in incidence, with rates universally increasing. When estimated separately for the first and second halves of the period, the median rates of increase were similar: 3.4% per annum and 3.3% per annum, respectively. However, rates of increase differed significantly between the first half and the second half for nine of the 21 registers with adequate coverage of both periods; five registers showed significantly higher rates of increase in the first half, and four significantly higher rates in the second half.

CONCLUSIONS/INTERPRETATION:

The incidence rate of childhood type 1 diabetes continues to rise across Europe by an average of approximately 3-4% per annum, but the increase is not necessarily uniform, showing periods of less rapid and more rapid increase in incidence in some registers. This pattern of change suggests that important risk exposures differ over time in different European countries. Further time trend analysis and comparison of the patterns in defined regions is warranted.

General practitioners' habits and knowledge in relation to the management of H. pylori-associated dyspepsia and their views about a locally available 13-carbon urea breath test

We report the results of general practitioners' views on Helicobacter pylori-associated dyspepsia and use of screening tests in the community. The use of office serology tests in screening is of concern as independent validation in specialist units has been disappointing.

A computerized audit of non-steroidal anti-inflammatory drug prescribing in general practice

The two group practices based in a city health centre decided to prescribe non-steroidal anti-inflammatory drugs in generic form from an agreed date. The practices' computer was used to identify the number of repeat prescriptions being issued for this group of drugs and to monitor the effectiveness of the changeover. Although both practices showed a marked increase in the level of generic prescribing there was considerable interpractice variation. Generic prescribing for one practice increased from 4% to 64% and for the other from 1% to 38% of repeat prescriptions issued for non-steroidal anti-inflammatory drugs over the study period. The reasons for this variation, the advantages of computerized audit and the problems associated with this self-imposed audit are discussed.

Repeat prescribing of non-steroidal anti-inflammatory drugs excluding aspirin:how careful are we?

About 5% of all National Health Service prescriptions in Britain and a quarter of reports of suspected adverse reactions are accounted for by non-steroidal anti-inflammatory drugs. Their prescription was investigated in two computerised group practices serving 11850 patients. Altogether 198 patients receiving repeat prescriptions of non-steroidal anti-inflammatory drugs were identified and relevant clinical details extracted from their notes. Of these patients, 119 were over 65 years old; 172 were receiving one of six different non-steroidal anti-inflammatory drugs; and 76 were taking drugs that can interact with non-steroidal anti-inflammatory drugs. Ninety one patients had one or more medical conditions that may be aggravated by non-steroidal anti-inflammatory drugs, and 36 had experienced side effects important enough for their treatment to be changed. A questionnaire to assess opinions and knowledge of non-steroidal anti-inflammatory drugs was given to 42 general practitioners and 26 rheumatologists. Although the two groups showed a comparable knowledge of the properties and costs of non-steroidal anti-inflammatory drugs, they differed significantly in their views on the circumstances under which these drugs should be used. Clear guidelines on the prescription of these drugs would indicate when careful monitoring is essential for patients to benefit from them safely.

Effect on prescribing of the limited list in a computerised group practice

The prescribing of drugs in the therapeutic classes that are affected by the government's limited list was investigated in a computerised group practice of just over 3,000 patients. Prescribable drugs in categories that are affected by the list were identified for two consecutive six month periods before and one six month period after the introduction of the list. A significant decrease in the prescribing of cough and cold remedies, vitamins, and antacids occurred after the list was introduced, whereas no change occurred in the prescribing of laxatives, benzodiazepines, or analgesics. The prescribing of iron and penicillin increased significantly after the list was introduced, whereas the use of H2 antagonists and non-steroidal anti-inflammatory drugs showed no significant change.

Size-fitting of Intravaginal Rings for Macaques and in vitro Release Kinetics of Zinc Finger Inhibitors

Background: Small molecule inhibitors of the zinc finger domain (ZFI) in the nucleocapsid protein (NCp7) of HIV-1 are potent inhibitors of HIV and SIV
replication and may have utility as topical products to prevent infection. Furthermore, intravaginal rings (IVRs) were developed as coitally-independent,
sustained release devices which could be used for administration of HIV microbicides. The aims of these studies were to demonstrate that IVRs sized for
macaques are practical and compatible with the current generation of thioester-based NCp7 inhibitors.

Methods: Non-medicated silicone elastomer vaginal rings of various sizes thought to be applicable for macaques were prepared and tested for vaginal fit in Pigtailed and Chinese Rhesus macaques. Macaques were monitored for 8 weeks for mucosal disruption by colposcopy and proinflammatory cytokine markers in cervical vaginal lavages (CVL) using Luminex bead-based technology. Three different ZFIs (compounds 52, 89 and 122, each derived from an N-substituted S-acyl-2-mercaptobenzamide thioester scaffold) were loaded at 50 mg into an optimal matrix-type ring design. In vitro continuous release studies were then conducted over 28 days and analyzed by HPLC. Rate of release was determined by linear regression analysis.

Results: Qualitative evaluation at the time of ring insertion suggested that the 25 mm ring provided optimal fit in both macaque species. All rings remained in
place during the study period (2 to 4 weeks), and the animals did not attempt to remove the rings. No tissue irritation was observed, and no signs of physical
discomfort were noted. Also, no significant induction of cervicovaginal proinflammatory markers was observed during the 8-week period during and following ring insertion. One Pigtailed macaque showed elevated IL-8 levels in the CVL during the period when the ring was in place; however, these levels were comparable to those observed in two control macaques. In vitro release of the ZFIs peaked at day 1 and then continually declined to near steady-state rates between 20-30 mcg/day. The percent release after 14 days was 2.9, 2.0 and 0.9 for ZFI 89, 52 and 122, respectively.

Conclusions: IVRs of 25mm diameter, determined to be the optimal size for macaques, were well tolerated and did not induce inflammation. Release of all ZFI compounds followed t 0.5 kinetics. These findings suggest that efficacy testing in primate models is warranted to fully evaluate the potential to prevent
transmission.

"They come with multiple morbidities":a qualitative assessment of pharmacist prescribing

This paper presents qualitative findings from a larger sequential mixed methods study which sought to provide an in-depth understanding of pharmacist prescribing from the perspective of pharmacist prescribers, medical colleagues and key stakeholders in Northern Ireland. Transcriptions were analyzed using thematic analysis as the interviews progressed and emergent themes were identified and coded (along with supporting quotes) independently and by consensus of the research team. Three major themes emerged in relation to pharmacist prescribing: the effect on patient care; challenges facing pharmacist prescribers and the importance of the interprofessional team (where two or more different professions with varied, yet complementary experience work together with a common purpose). Pharmacist prescribing may have the potential to reduce the medication burden for patients (as reported by pharmacists) as pharmacists tend to provide a more comprehensive medication review than doctors; the additional time for consultations made this possible. Further research is required on how interprofessional team working can be maximized in the context of pharmacist prescribing, particularly in relation to the management of multi-morbidity.