Patient safety incidents in Irish general practice during the COVID-19 pandemic: an exploratory practice level analysis.

BACKGROUND: Patient safety is defined as the prevention of harm to patients and aims to prevent errors. This analysis explores factors associated with the reported occurrence of patient safety incidents (PSIs) in general practices in Ireland at the start of the COVID-19 pandemic. METHODS: The PRICOV-19 was a cross-sectional study to record the (re)organisation of care provided in general practice and changes implemented during the COVID-19 pandemic in 38 countries. Primary outcomes include three potential scenarios of PSIs: delayed care due to practice factors, delayed care due to patient factors, and delayed care due to triage. Exploratory variables included demographic and organisational characteristics, triage, collaboration, and strategies to safeguard staff members' well-being. RESULTS: Of the 172 participating Irish general practices, 71% (n = 122) recorded at least one potential PSI. The most frequent incident was delayed care due to patient factors (65%), followed by practice (33%) and triage (30%). Multivariate analysis showed that delayed care due to patient factors was associated with changes in the process of repeat prescriptions (OR 6.7 [CI 95% 2.5 to 19.6]). Delayed care due to practice factors was associated with suburbs/small towns (OR 4.2 [1.1 to 19.8]) and structural changes to the reception (OR 3.5 [1.2 to 11.4]). While delayed care due to patient factors was associated with having a practice population of 6000-7999 patients (OR 4.7 [1.1 to 27.6]) and delayed care due to practice factors was associated with having a practice population of 2000-3999 patients (OR 4.2 [1.2 to 17.1]). No linear associations were observed with higher or lower patient numbers for any factor. Delayed care due to triage was not associated with any exploratory variables. CONCLUSION: The COVID-19 pandemic resulted in dramatic changes in the delivery of care through general practices in Ireland. Few factors were associated with the reported occurrence of PSIs, and these did not show consistent patterns. Sustained improvements were made in relation to repeat prescriptions. The lack of consistent patterns, potentially confirms that the autonomous decisions made in general practice in response to the challenges of the COVID-19 pandemic could have benefitted patient safety (See Graphical abstract).

Screening for and Disclosure of Domestic Violence during the COVID-19 Pandemic: Results of the PRICOV-19 Cross-Sectional Study in 33 Countries.

The COVID-19 pandemic left no one untouched, and reports of domestic violence (DV) increased during the crisis. DV victims rarely seek professional help, yet when they do so, they often disclose it to their general practitioner (GP), with whom they have a trusting relationship. GPs rarely screen and hence rarely take the initiative to discuss DV with patients, although victims indicate that offering this opportunity would facilitate their disclosure. This paper aims to describe the frequency of screening for DV by GPs and disclosure of DV by patients to the GP during the COVID-19 pandemic, and to identify key elements that could potentially explain differences in screening for and disclosure of DV. The PRICOV-19 data of 4295 GP practices from 33 countries were included in the analyses, with practices nested in countries. Two stepwise forward clustered ordinal logistic regressions were performed. Only 11% of the GPs reported (much) more disclosure of DV by patients during COVID-19, and 12% reported having screened for DV (much). Most significant associations with screening for and disclosure of DV concerned general (pro)active communication. However, (pro)active communication was performed less frequently for DV than for health conditions, which might indicate that GPs are insufficiently aware of the general magnitude of DV and its impact on patients and society, and its approach/management. Thus, professional education and training for GPs about DV seems highly and urgently needed.

Heartwatch: an Irish cardiovascular secondary prevention programme in primary care, a secondary analysis of patient outcomes.

OBJECTIVES: To investigate patient follow-up data from Heartwatch: Ireland's secondary prevention programme for cardiovascular disease delivered in general practice. DESIGN: Retrospective descriptive study based on secondary analysis of routinely collected data from Heartwatch. SETTING: Heartwatch targeted 20% of general practices in Ireland and recruited 475 general practitioners across 325 practices. PARTICIPANTS: The patient population included people with a history of acute myocardial infarction, percutaneous transluminal coronary angioplasty or a coronary artery bypass graft. Over 16 000 patients entered the programme however, to assess the long-term progress of patients, we identified a cohort of 5700 patients with at least 8 years in the programme. INTERVENTIONS: A standard protocol for continuing care of patients for the secondary prevention of cardiovascular disease was administered by general practices. The programme was designed using WHO and European Society of Cardiology guidelines on secondary prevention. OUTCOME MEASURES: A Continuing Care (CCare) score out of eight was the primary outcome measure used. It was calculated based on programme targets for well-known cardiovascular risk factors: exercise, systolic blood pressure, LDL cholesterol, optimally controlled glucose, smoking status, and pharmacological treatment. RESULTS: After 1 year, 37% of the 8-year cohort had achieved a CCare score >5 increasing to 44% after year 8. Patient sex was predictive of better scores; male patients had almost a half-point advantage (0.432, 99% CI: 0.335 to 0.509). Patients who enrolled earlier following their qualifying event and patients with more frequent visits were also more likely to achieve higher CCare scores. CONCLUSIONS: Overall, patients are not likely to meet all targets set by secondary prevention guidelines, however, supporting patient self-management may impact on this. Early enrolment after a cardiac event and frequent structured care visits should be priorities in the design and implementation of similar programmes. Ongoing evaluation of them is necessary to improve outcomes.

Variation in suspected cancer referral pathways in primary care: comparative analysis across the International Benchmarking Cancer Partnership.

BACKGROUND: International variations in cancer outcomes persist and may be influenced by differences in the accessibility and organisation of cancer patient pathways. More evidence is needed to understand to what extent variations in the structure of primary care referral pathways for cancer investigation contribute to differences in the timeliness of diagnoses and cancer outcomes in different countries. AIM: To explore the variation in primary care referral pathways for the management of suspected cancer across different countries. DESIGN AND SETTING: Descriptive comparative analysis using mixed methods across the International Cancer Benchmarking Partnership (ICBP) countries. METHOD: Schematics of primary care referral pathways were developed across 10 ICBP jurisdictions. The schematics were initially developed using the Aarhus statement (a resource providing greater insight and precision into early cancer diagnosis research) and were further supplemented with expert insights through consulting leading experts in primary care and cancer, existing ICBP data, a focused review of existing evidence on the management of suspected cancer, published primary care cancer guidelines, and evaluations of referral tools and initiatives in primary care. RESULTS: Referral pathway schematics for 10 ICBP jurisdictions were presented alongside a descriptive comparison of the organisation of primary care management of suspected cancer. Several key areas of variation across countries were identified: inflexibility of referral pathways, lack of a managed route for non-specific symptoms, primary care practitioner decision-making autonomy, direct access to investigations, and use of emergency routes. CONCLUSION: Analysing the differences in referral processes can prompt further research to better understand the impact of variation on the timeliness of diagnoses and cancer outcomes. Studying these schematics in local contexts may help to identify opportunities to improve care and facilitate discussions on what may constitute best referral practice.

Participation rate in cervical cancer screening in general practice related to the proximity of gynecology care facilities: A 3 year follow-up cohort study.

Cervical cancer screening (CCS) by Pap tests is mainly performed by gynecologists in France, but also by general practitioners (GPs) and midwives. The screening uptake is insufficient to reduce the incidence of cervical neoplasms. Our aim was to investigate the association between screening rates in patients listed with GPs and the distance between GPs' offices and gynecology facilities. The population of 345 GPs, and their 93,918 female patients eligible for screening over 3 years (2013-2015), were derived from the Health Insurance claim database. We estimated the socioeconomic level of the geographical area of GPs' offices using the European Deprivation Index (EDI). The proximity of gynecology facilities was calculated by computing their distance from GPs' offices (in order to adjust the proximity of gynecology facilities with EDI and performance of smears by the GP). The number of gynecologists within 5 km of a GP's office was associated with the CCS rate increasing by 0.31% for every unit increase in the density of gynecologists within 5 km (p < 0.0001). The close proximity of gynecology facilities was not significantly associated with screening uptake among female patients when the office of the GP where they were registered was settled in a deprived area.

'There's this big fear around palliative care because it's connected to death and dying': A qualitative exploration of the perspectives of undergraduate students on the role of the speech and language therapist in palliative care.

BACKGROUND: Speech and language therapy in palliative care is a developing discipline of clinical practice. Research literature has highlighted that undergraduate palliative care education in speech and language therapy is inconsistent and inadequate. However, limited research has been carried out to date in relation to student speech and language therapists and palliative care. AIM: To explore the role of speech and language therapists in palliative care from the perspective of speech and language therapy students in Ireland. DESIGN: A qualitative descriptive research study was conducted, involving focus group interviews. SETTING/PARTICIPANTS: Purposive sampling was used to recruit 12 student speech and language therapists from one university site for this study. Undergraduate second, third and fourth year students were eligible for inclusion. RESULTS: This study revealed that undergraduate student speech and language therapists collectively agree that there is a role for speech and language therapy in palliative care. Although students acknowledged that speech and language therapists can make a positive difference to patients' lives, and academic lectures were positively received, insufficient exposure to palliative care has resulted in fear, uncertainty and a lack of confidence amongst student speech and language therapists. CONCLUSIONS: A greater emphasis on palliative care is needed in undergraduate speech and language therapy education to ensure confidence and competency development. An exploration of student speech and language therapists' experiences in a specialist palliative care unit would be advantageous to determine the appropriateness of this setting for clinical placements.

General practitioners' deprescribing decisions in older adults with polypharmacy: a case vignette study in 31 countries.

BACKGROUND: General practitioners (GPs) should regularly review patients' medications and, if necessary, deprescribe, as inappropriate polypharmacy may harm patients' health. However, deprescribing can be challenging for physicians. This study investigates GPs' deprescribing decisions in 31 countries. METHODS: In this case vignette study, GPs were invited to participate in an online survey containing three clinical cases of oldest-old multimorbid patients with potentially inappropriate polypharmacy. Patients differed in terms of dependency in activities of daily living (ADL) and were presented with and without history of cardiovascular disease (CVD). For each case, we asked GPs if they would deprescribe in their usual practice. We calculated proportions of GPs who reported they would deprescribe and performed a multilevel logistic regression to examine the association between history of CVD and level of dependency on GPs' deprescribing decisions. RESULTS: Of 3,175 invited GPs, 54% responded (N = 1,706). The mean age was 50 years and 60% of respondents were female. Despite differences across GP characteristics, such as age (with older GPs being more likely to take deprescribing decisions), and across countries, overall more than 80% of GPs reported they would deprescribe the dosage of at least one medication in oldest-old patients (> 80 years) with polypharmacy irrespective of history of CVD. The odds of deprescribing was higher in patients with a higher level of dependency in ADL (OR =1.5, 95%CI 1.25 to 1.80) and absence of CVD (OR =3.04, 95%CI 2.58 to 3.57). INTERPRETATION: The majority of GPs in this study were willing to deprescribe one or more medications in oldest-old multimorbid patients with polypharmacy. Willingness was higher in patients with increased dependency in ADL and lower in patients with CVD.

Minor surgery in general practice in Ireland- a report of workload and safety.

BACKGROUND: The provision of minor surgical services is an established part of the task profile of general practitioners (GPs) in many countries in Europe and elsewhere. This study aimed to collect data on the clinical process and outcomes for specified minor surgical procedures undertaken in Irish general practice by GPs experienced in minor surgery in order to document the scope and safety of minor surgery being undertaken. METHODS: Over a six-month period, 24 GPs in 20 practices recorded data on a pre-determined list of procedures undertaken in adults (aged 18 and older); procedures for ingrown toenails were also recorded for those aged 12-18 years. Clinical data were rendered fully anonymous by the participating GPs, entered onto the Excel database template and returned to the project team monthly. RESULTS: On average, each practice undertook 212 procedures in a six-month period. The four most frequent procedures include two relatively non-invasive procedures (cryosurgical ablation of skin lesions and aspiration and/or injection of joints) and two more invasive procedures (full thickness excision of skin lesion and shave, punch or incisional biopsy). Overall, 83.8% of relevant specimens were submitted for histology. Combining benign and malignant cases, there was an overall 87% clinical and histological concordance; 85% of malignancies were suspected clinically. A complication was recorded in 0.9% after 1 month. CONCLUSIONS: Irish GPs with experience in minor surgery can provide a range of surgical services in the community safely.

The association between cervical cancer screening participation and the deprivation index of the location of the family doctor's office.

BACKGROUND: Cervical cancer screening rates are known to be strongly associated with socioeconomic status. Our objective was to assess whether the rate is also associated with an aggregated deprivation marker, defined by the location of family doctors' offices. METHODS: To access this association, we 1) collected data from the claim database of the French Health Insurance Fund about the registered family doctors and their enlisted female patients eligible for cervical screening; 2) carried out a telephone survey with all registered doctors to establish if they were carrying out Pap-smears in their practices; 3) geotracked all the doctors' offices in the smallest existing blocks of socioeconomic homogenous populations (IRIS census units) that were assigned a census derived marker of deprivation, the European Deprivation Index (EDI), and a binary variable of urbanization; and 4) we used a multivariable linear mixed model with IRIS as a random effect. RESULTS: Of 348 eligible doctors, 343 responded to the telephone survey (98.6%) and were included in the analysis, encompassing 88,152 female enlisted patients aged 25-65 years old. In the multivariable analysis (adjusted by the gender of the family doctor, the practice of Pap-smears by the doctor and the urbanization of the office location), the EDI of the doctor's office was strongly associated with the cervical cancer screening participation rate of eligible patients (p<0.001). CONCLUSION: The EDI linked to the location of the family doctor's office seems to be a robust marker to predict female patients' participation in cervical cancer screening.

Patient Characteristics and General Practitioners' Advice to Stop Statins in Oldest-Old Patients: a Survey Study Across 30 Countries.

BACKGROUND: Statins are widely used to prevent cardiovascular disease (CVD). With advancing age, the risks of statins might outweigh the potential benefits. It is unclear which factors influence general practitioners' (GPs) advice to stop statins in oldest-old patients. OBJECTIVE: To investigate the influence of a history of CVD, statin-related side effects, frailty and short life expectancy, on GPs' advice to stop statins in oldest-old patients. DESIGN: We invited GPs to participate in this case-based survey. GPs were presented with 8 case vignettes describing patients > 80 years using a statin, and asked whether they would advise stopping statin treatment. MAIN MEASURES: Cases varied in history of CVD, statin-related side effects and frailty, with and without shortened life expectancy (< 1 year) in the context of metastatic, non-curable cancer. Odds ratios adjusted for GP characteristics (ORadj) were calculated for GPs' advice to stop. KEY RESULTS: Two thousand two hundred fifty GPs from 30 countries participated (median response rate 36%). Overall, GPs advised stopping statin treatment in 46% (95%CI 45-47) of the case vignettes; with shortened life expectancy, this proportion increased to 90% (95CI% 89-90). Advice to stop was more frequent in case vignettes without CVD compared to those with CVD (ORadj 13.8, 95%CI 12.6-15.1), with side effects compared to without ORadj 1.62 (95%CI 1.5-1.7) and with frailty (ORadj 4.1, 95%CI 3.8-4.4) compared to without. Shortened life expectancy increased advice to stop (ORadj 50.7, 95%CI 45.5-56.4) and was the strongest predictor for GP advice to stop, ranging across countries from 30% (95%CI 19-42) to 98% (95% CI 96-99). CONCLUSIONS: The absence of CVD, the presence of statin-related side effects, and frailty were all independently associated with GPs' advice to stop statins in patients aged > 80 years. Overall, and within all countries, cancer-related short life expectancy was the strongest independent predictor of GPs' advice to stop statins.

An online survey of Irish general practitioner experience of and attitude toward managing problem alcohol use.

BACKGROUND: In the general practice setting screening, brief intervention and counselling have been shown to be effective in the reduction of problem alcohol use. This study aimed to explore Irish general practitioners' (GPs) current practice of and attitudes towards the management of problem alcohol use. METHODS: An online survey was emailed, with one email reminder, to 1750 general/family practitioners who were members of the Irish College of General Practitioners (ICGP) and for whom an active email address was available. Overall, 476 completed questionnaires were received representing a 27.2% response rate. RESULTS: Two-thirds of the respondents reported that they have managed patients for problem alcohol use and related issues in the past year. The majority, 96%, of respondents indicated that they initiate conversations around alcohol even when the patient does not do so. Almost two thirds of GPs stated that they use structured brief intervention when talking to patients about their alcohol intake and circa 85% reported that they provide some form of counselling in relation to reducing alcohol consumption. While more than two out of three GPs felt prepared when counselling patients in relation to alcohol consumption, almost half considered they are ineffective in helping patients to reduce alcohol consumption. One third of GPs advised that they did not have access to an addiction counsellor. CONCLUSIONS: GPs in this survey reported widespread experience of screening and intervention, however, many still felt ineffective. In order to maximise the potential impact of GPs, a clearer understanding is required of what interventions are effective in different scenarios. Furthermore, GPs are only part of the solution in terms of addressing alcohol consumption. The services available in the broader health care system and Government alcohol related policy needs to further support GPs and patients.

Developing accreditation for community based surgery: the Irish experience.

Purpose Carrying out minor surgery procedures in the primary care setting is popular with patients, cost effective and delivers at least as good outcomes as those performed in the hospital setting. This paper aims to describe the central role of clinical leadership in developing an accreditation system for general practitioners (GPs) undertaking community-based surgery in the Irish national setting where no mandatory accreditation process currently exists. Design/methodology/approach In all, 24 GPs were recruited to the GP network. Ten pilot standards were developed addressing GPs' experience and training, clinical activity and practice supporting infrastructure and tested, using information and document review, prospective collection of clinical data and a practice inspection visit. Two additional components were incorporated into the project (patient satisfaction survey and self-audit). A multi-modal evaluation was undertaken. A majority of GPs was included at all stages of the project, in line with the principles of action learning. The steering group had a majority of GPs with relevant expertise and representation of all other actors in the minor surgery arena. The GP research network contributed to each stage of the project. The project lead was a GP with minor surgery experience. Quantitative data collected were analysed using Predictive Analytic SoftWare. Krueger's framework analysis approach was used to analyse the qualitative data. Findings A total of 9 GPs achieved all standards at initial review, 14 successfully completed corrective actions and 1 GP did not achieve the required standard. Standards were then amended to reflect findings and a supporting framework was developed. Originality/value The flexibility of the action-learning approach and the clinical leadership design allowed for the development of robust quality standards in a short timeframe.

The Use of Routine Postoperative Microscopy and Culture Screening Following Elective Hip and Knee Arthroplasty: An Unnecessary Cost With No Effect on Clinical Management?

BACKGROUND: The use of microscopy and culture screening to detect pathogenic microorganisms followed by a decolonization protocol is a widely performed practice prior to elective hip and knee arthroplasty. In our center, the routine care of hip and knee arthroplasty also involves postoperative screening including direct culture of the surgical site. The aim of this study was to assess the frequency of pathogen detection following these tests and to determine whether routine postoperative screening, with particular reference to postoperative surgical site culture, led to any change in clinical management of these patients. METHODS: A series of 1000 patients undergoing hip or knee arthroplasty at The Mater Hospital between January 2014 and December 2015 were identified from our arthroplasty database. Results of preoperative and postoperative microscopy and culture screening were reviewed by 2 independent researchers. RESULTS: Of the 1000 subjects, positive microscopy and culture results were identified in 88 patients (8.8%) preoperatively and 5 patients (0.5%) postoperatively. None of the 1000 postoperative surgical site swabs had a positive microscopy and culture screen. All the 5 positive postoperative microscopy and culture screen results were in patients who had positive cultures preoperatively. There were no positive postoperative microscopy and culture screen results in patients who had had negative preoperative results. Postoperative screening was performed at a cost of AUS$213 per patient. CONCLUSION: Routine postoperative surgical site culture following hip and knee arthroplasty does not alter clinical management, has a significant associated financial cost, and has the potential to expose the patient to a risk of surgical site infection and is therefore not supported.

Effectiveness of motivational interviewing in influencing smoking cessation in pregnant and postpartum disadvantaged women.

INTRODUCTION: Systematic assessments of Motivational Interviewing (MI) in smoking behavior have been rare to date. This study aimed to determine whether an integrated approach, involving staff training in MI techniques, was sufficient to affect change in smoking status or intensity in low-income pregnant and postpartum women. METHODS: Overall, 500 consecutive smokers were recruited at first prenatal visit to public antenatal clinics. Following staff training, 500 more were recruited (intervention group). Data were recorded at 28-32 weeks gestation, after birth, at 3-4 and 7-9 months postpartum. The primary outcome measure was self-reported continued abstinence from smoking verified by urinary cotinine analysis. Changes in smoking intensity were also measured. RESULTS: There was no significant difference in the proportion of smokers in the intervention and control groups who reported stopping smoking at 28-32 weeks gestation (8.2% vs. 8.8%; p = .73), 1 week after birth (8.6% vs. 11.4%; p = .14), 3-4 months after birth (5.8% vs. 4.8%; p = .48), or 7-9 months after birth (5.2% vs. 4.0%; p = .36). Although more cases were nonsmoking at the second visit, 14.8% [95% CI = 11.8-18.5] vs. 13.1% controls [95% CI = 10.3-16.6], this was not statistically significant. CONCLUSIONS: MI delivered at a number of time points during pregnancy and up to 9 months postpartum failed to affect quit rates. It may have had a small effect in preventing relapse among spontaneous quitters in late pregnancy though the validity of this remains uncertain.

Attitudes toward preventive services and lifestyle: the views of primary care patients in Europe. the EUROPREVIEW patient study.

BACKGROUND: For preventive interventions in general practice to succeed, patients' points of view must be taken into account in addition to those of GPs. OBJECTIVE: To explore patients' views and beliefs about the importance of lifestyle and preventive interventions, to assess their readiness to make changes to their lifestyle and their willingness to receive support from GPs. METHODS: Cross-sectional survey conducted by EUROPREV in primary care practices in 22 European countries. Patients were consecutively selected and interviewed from September 2008 to September 2009. RESULTS: Seven thousand nine hundred and forty-seven participants, 52.2% females. Only 30.5% of risky drinkers think they need to change, as opposed to 64% of smokers, 73.5% of patients with unhealthy eating habits and 73% with lack of physical activity. Risky drinkers reported that GPs initiated a discussion on alcohol consumption less often (42%) than on smoking (63%), eating habits (59%) or physical activity (55%). Seventy-five per cent, 66% and 63% of patients without hypertension, diabetes or hypercholesterolaemia, respectively, think blood pressure, blood sugar and serum cholesterol should be checked yearly. Women (80%) think they should be screened with the cervical smear test and 72.8% of women aged 30-49 years with mammography, yearly or every 2 years. CONCLUSIONS: A high proportion of patients attending primary care with unhealthy lifestyles (especially risky drinkers) do not perceive the need to change their habits, and about half the patients reported not having had any discussion on healthy lifestyles with their GPs. Patients overestimate their need to be screened for cardiovascular risk factors and for cancer.

Heartwatch: the effect of a primary care-delivered secondary prevention programme for cardiovascular disease on medication use and risk factor profiles.

BACKGROUND: Heartwatch is a secondary prevention programme of coronary heart disease (CHD) in primary care in Ireland. The aim was to further examine the effect of the Heartwatch programme on cardiovascular risk factors and treatments of patients with a follow-up of 3.5 years. DESIGN: Prospective cohort study of 12,358 patients with established CHD (myocardial infarction, percutaneous cardiac intervention, coronary artery bypass graft) recruited by participating general practitioners; patients invited to attend on a quarterly basis, with continuing care implemented according to defined clinical protocols. METHODS: Changes in risk factors and treatments at 1, 2, 3 and 3.5-year follow-up from baseline were made using paired t-test for continuous and McNemar's test for categorical data. RESULTS: Important changes in systolic and diastolic blood pressure, total and low-density lipoprotein cholesterol and smoking status were observed at 1, 2, 3 and 3.5 years (P < 0.0001) with significant increase in proportions of patients within the target. However, changes in body mass index were small, with no significant improvement in waist circumference. There was a significant increase in prescription of secondary preventive medications and good patient compliance. Males were more likely to be within the target for systolic blood pressure, total cholesterol, waist circumference and exercise level at 3.5 years, but less likely for body mass index. CONCLUSION: Studies of cardiac rehabilitation without any follow-up programmes show that over time patients revert in part to previous lifestyle habits; this primary care-delivered programme has shown sustained improvements in major risk factors, particularly smoking, blood pressure and cholesterol, and treatments for CHD. Weight management presents a greater challenge.

GP-delivered secondary prevention cardiovascular disease programme; early predictors of likelihood of patient non-adherence.

INTRODUCTION: The aim of this study was to determine how routinely recorded data could predict early the likelihood of patient non-adherence to a primary care-delivered secondary prevention programme for established coronary heart disease (CHD), with patients with CHD (10,851) invited to attend four times per year. METHOD: Non-adherence was defined as attending no more than three GP visits ever. The study sample was selected to allow a possible two-year recorded follow-up period in which patients could take up invitations. Administrative recordings of visit dates and intervals between visits, baseline results of key parameters and early changes were examined using logistic regression to determine independent predictors of non-adherence. RESULT: Longer interval between early visits, no family history of CHD, smoking and being outside target for exercise at baseline were independently associated with non-adherence. CONCLUSION: Early identification by GPs of those who fail to attend on time or who defer appointments, in addition to persistence of lifestyle factors unchanged by a prior serious cardiac event should serve as a warning sign that targeted interventions to maintain adherence in primary care-delivered secondary prevention programmes are necessary.

All azoospermic males should be screened for cystic fibrosis mutations before intracytoplasmic sperm injection.

We assessed the frequency of CFTR mutations in groups with varying degrees of sub-fertility and compared these groups to a fertile male group with proven paternity. Screening for CFTR mutations should be routine for all azoospermic males, irrespective of obstructive or non-obstructive etiology, prior to proposing ICSI treatment. CFTR testing has no value in the investigation of non-azoospermic infertile males.

Excretion and metabolism of lersivirine (5-{[3,5-diethyl-1-(2-hydroxyethyl)(3,5-14C2)-1H-pyrazol-4-yl]oxy}benzene-1,3-dicarbonitrile), a next-generation non-nucleoside reverse transcriptase inhibitor, after administration of [14C]Lersivirine to healthy volunteers.

Lersivirine [UK-453,061, 5-((3,5-diethyl-1-(2-hydroxyethyl)(3,5-14C2)-1H-pyrazol-4-yl)oxy)benzene-1,3-dicarbonitrile] is a next-generation non-nucleoside reverse transcriptase inhibitor, with a unique binding interaction within the reverse transcriptase binding pocket. Lersivirine has shown antiviral activity and is well tolerated in HIV-infected and healthy subjects. This open-label, Phase I study investigated the absorption, metabolism, and excretion of a single oral 500-mg dose of [14C]lersivirine (parent drug) and characterized the plasma, fecal, and urinary radioactivity of lersivirine and its metabolites in four healthy male volunteers. Plasma C(max) for total radioactivity and unchanged lersivirine typically occurred between 0.5 and 3 h postdose. The majority of radioactivity was excreted in urine (approximately 80%) with the remainder excreted in the feces (approximately 20%). The blood/plasma ratio of total drug-derived radioactivity [area under the plasma concentration-time profile from time zero extrapolated to infinite time (AUC(inf))] was 0.48, indicating that radioactive material was distributed predominantly into plasma. Lersivirine was extensively metabolized, primarily by UDP glucuronosyltransferase- and cytochrome P450-dependent pathways, with 22 metabolites being identified in this study. Analysis of precipitated plasma revealed that the lersivirine-glucuronide conjugate was the major circulating component (45% of total radioactivity), whereas unchanged lersivirine represented 13% of total plasma radioactivity. In vitro studies showed that UGT2B7 and CYP3A4 are responsible for the majority of lersivirine metabolism in humans.

The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

AIMS: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a London University teaching hospital. Maternal IGF-1, IGF-2 and IGFBP-3 were measured in maternal blood at booking and analyzed with respect to gestational age at delivery. RESULTS: There was no significant association between maternal IGF-1 or IGF-2 and preterm birth (PTB). A significant reduction in mean IGFBP-3 levels was noted with delivery <32 completed weeks (P=0.02). CONCLUSION: Maternal mean IGFBP-3 levels are significantly reduced in cases complicated by delivery <32 completed weeks.