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The rodent parasite Plasmodium chabaudi is an important in vivo model of malaria. The ability to produce chronic infections makes it particularly useful for investigating the development of anti- Plasmodium immunity, as well as features associated with parasite virulence during both the acute and chronic phases of infection. P. chabaudi also undergoes asexual maturation (schizogony) and erythrocyte invasion in culture, so offers an experimentally-amenable in vivo to in vitro model for studying gene function and drug activity during parasite replication. To extend the usefulness of this model, we have further optimised transfection protocols and plasmids for P. chabaudi and generated stable, fluorescent lines that are free from drug-selectable marker genes. These mother-lines show the same infection dynamics as wild-type parasites throughout the lifecycle in mice and mosquitoes; furthermore, their virulence can be increased by serial blood passage and reset by mosquito transmission. We have also adapted the large-insert, linear Plasmo GEM vectors that have revolutionised the scale of experimental genetics in another rodent malaria parasite and used these to generate barcoded P. chabaudi gene-deletion and -tagging vectors for transfection in our fluorescent P. chabaudi mother-lines. This produces a tool-kit of P. chabaudi lines, vectors and transfection approaches that will be of broad utility to the research community., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Marr EJ et al.)

The rodent parasite Plasmodium chabaudi is an important in vivo model of malaria. The ability to produce chronic infections makes it particularly useful for investigating the development of anti- Plasmodium immunity, as well as features associated with parasite virulence during both the acute and chronic phases of infection. P. chabaudi also undergoes asexual maturation (schizogony) and erythrocyte invasion in culture, so offers an experimentally-amenable in vivo to in vitro model for studying gene function and drug activity during parasite replication. To extend the usefulness of this model, we have further optimised transfection protocols and plasmids for P. chabaudi and generated stable, fluorescent lines that are free from drug-selectable marker genes. These mother-lines show the same infection dynamics as wild-type parasites throughout the lifecycle in mice and mosquitoes; furthermore, their virulence can be increased by serial blood passage and reset by mosquito transmission. We have also adapted the large-insert, linear Plasmo GEM vectors that have revolutionised the scale of experimental genetics in another rodent malaria parasite and used these to generate barcoded P. chabaudi gene-deletion and -tagging vectors for transfection in our fluorescent P. chabaudi mother-lines. This produces a tool-kit of P. chabaudi lines, vectors and transfection approaches that will be of broad utility to the research community., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Marr EJ et al.)

Aims: In the UK, adverse drug reactions (ADRs) are responsible for over 6.5% of all hospital admissions, representing a significant morbidity and cost burden to the health service. We aimed to develop an ADR monitoring system capable of identifying the reasons for patient discontinuation of drug therapy within 6 months of the index prescription., Methods: Patients first prescribed amlodipine between 1 March 2004 and 28 February 2007 who discontinued their amlodipine medication within 6 months of the index prescription were identified from the practice team information (PTI) database. Once identified, reasons for amlodipine discontinuation were assessed by an electronic database search using relevant Readcodes and key words and by a direct approach to the primary care medical records., Results: The PTI database identified 995 patients [61.4% females, mean age 65.9 years (SD 12.4 years)] who discontinued amlodipine within 6 months of an index prescription. An electronic search of the database, using Readcodes, identified that 19.4% (193) of patients who discontinued their medication had an ADR recorded in the database. Six (20%) of 30 participating primary care practices, contributing to the PTI database, agreed to be approached directly and supply the reasons for discontinuation for the 51 patients identified as having discontinued amlodipine in their practices. Completed data were returned for all 51 patients, 98% of whom discontinued amlodipine due to an ADR or adverse drug event., Conclusions: The results of this study confirm that primary care prescribing databases can be easily used to identify the frequency and nature of ADRs occurring in an ADR-enriched population identified through medication discontinuation., (© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.)

Aims: To determine the extent of combined oral contraceptive use by girls aged 10-16 years in Scotland., Methods: Assessment of combined oral contraceptive prescribing in 35 414 girls for the year 1 November 1999-31 October 2000 from data retrieved from 161 primary care practices taking part in the Scottish Programme for Improving Clinical Effectiveness in Primary Care, and from national aggregated data from family planning clinics., Results: During the study period the oral contraceptive pill (OCP) was prescribed by a primary care physician to 1531 girls (4.3%) aged 10-16 years. The age specific prevalence rates per 1000 girls registered with their family doctor rose from 0.9/1000 girls aged 12 years or younger, to 6.9, 30, 86.3, and 174.8/1000 for girls aged 13, 14, 15, and 16 years respectively. The overall prevalence of combined oral contraceptive prescribing by primary care physicians was 43.2/1000 girls aged 10-16 years. A further 1765 girls aged 13-16 years obtained a prescription for the OCP from a Scottish family planning clinic, giving an overall prevalence rate for family planning clinic prescribing of 8.0/1000 girls aged 10-16 years. Despite reportedly high levels of sexual activity and teenage pregnancy in this age group, these results confirm that OCP use is relatively low., Conclusions: The UK has the highest rate of teenage pregnancy in Western Europe, but despite the medical and social concerns about the sexual health of teenagers, the level of oral contraceptive use in this young age group remains low.

Aims: To investigate the extent of acute coprescribing in primary care to children on chronic antiepileptic therapy, which could give rise to potentially harmful drug-drug interactions., Design: Acute coprescribing to children on chronic antiepileptic drug therapy in primary care was assessed in 178 324 children aged 0-17 years for the year 1 November 1999 to 31 October 2000. Computerized prescribing data were retrieved from 161 representative general practices in Scotland., Setting: One hundred and sixty-one general practices throughout Scotland., Results: During the study year 723 (0.41%) children chronically prescribed antiepileptic therapy were identified. Fourteen antiepileptic agents were prescribed, with carbamazepine, sodium valproate and lamotrigine accounting for 80% of the total. During the year children on chronic antiepileptic therapy were prescribed 4895 acute coprescriptions for 269 different medicines. The average number of acute coprescriptions for non-epileptic drug therapy were eight, 11, six, and six for the 0-1, 2-4, 5-11, and 12-17-year-olds, respectively. Of these acute coprescriptions 72 (1.5%) prescribed to 22 (3.0%) children were identified as a potential source of clinically serious interactions. The age-adjusted prevalence rates for potentially serious coprescribing were 86, 26, 22, and 33/1000 children chronically prescribed antiepileptic therapy in the 0-1, 2-4, 5-11, and 12-17-year-old age groups, respectively. The drugs most commonly coprescribed which could give rise to such interactions were antacids, erythromycin, ciprofloxacin, theophylline and the low-dose oral contraceptive. For 10 (45.5%0 of the 20 children identified at risk of a potentially clinically serious adverse drug interaction, the acute coprescription was prescribed off label because of age or specific contraindication/warning., Conclusions: In primary care, 3.0% of children on chronic antiepileptic therapy are coprescribed therapeutic agents, which could give rise to clinically serious drug-drug interactions.

Study Objective: To create a national data resource for studying morbidity in Scottish general practice, complementary to existing information systems and available for management and research purposes at national and local levels., Design: The Department of General Practice, University of Aberdeen has worked since 1988 to collect and analyse computerised information at practice, regional, and national levels by distribution of a floppy disk-based software program, which extracts a predetermined dataset from each general practice computer system., Setting: Almost 100% of patients in Scotland are registered with a general practitioner. Scotland has a national computer system, General Practice Administration System for Scotland (GPASS), used by over 75% of all Scottish practices. Escalating costs of health care and demographic changes in the national population emphasise the monetary value of the gatekeeper role of general medical practice. General practitioners' increasing involvement in the provision and purchasing of care has raised the importance of the management of populations as well as the care of individual patients., Patients: Collection of major morbidity and prescribing data from up to 2.4 million patients, approximately half the population of Scotland, takes place biannually. A subset of practices (population 282,700 patients; 52 practices) are continuously collecting doctor/patient contact information (symptoms or diagnoses)., Main Results: The data collected provide information at the level of the individual patient. Morbidity, prescribing, screening, and administrative data can be linked by patient, date or postcode. The sample population studied is representative by age, sex, deprivation, and sparsity (using the postcode) of the national population. Large sub-populations of patients satisfying a selected criteria can be extracted for further study of needs assessment or of epidemiological research., Conclusions: The gatekeeping role of Scottish general practice and the predominance of GPASS favours standardisation of methods of data capture and the construction of large regional, national, and Continuous Morbidity databases. Analysis by geographical, demographic, and temporal distributions allows the changing patterns of illness and provision of health care to be studied in substantial detail to the benefit of patients, doctors, and the national health service.

A questionnaire concerning blood pressure assessment, as part of health promotion activity, was circulated to all 770 Gpass practices in Scotland producing a 64.6% response rate. The results reveal a wide range in both the systolic and diastolic levels chosen to classify blood pressure as normal, borderline raised or raised. Practices are using a variety of values to indicate hypertension when considering systolic and, to a lesser extent, diastolic pressure. The variations found suggest that both over and under treatment are a significant risk to patients. The introduction of the 1993 health promotion regulations means that practices are required to actively target their practice population for blood pressure assessment and appropriate intervention. We suggest that this process will be enhanced if doctors are encouraged to adopt the established guidelines for the classification of blood pressure or general practice computer software is adopted to offer blood pressure protocol support.

Background: A high proportion of Scottish general practices use a standard computer software package (GPASS, general practice administration system for Scotland), and thus, Scotland is uniquely placed to amalgamate primary care data on a national scale. Practices, however, vary widely in the nature and extent of data entered on computer and a major limitation on the use of the collected data is the absence of information on the completeness and accuracy of the computer database., Aim: This study set out to assess the quality of morbidity and repeat prescribing records held on computer by general practices in Scotland., Method: Forty-one practices, with above average levels of morbidity data recorded on computer, were selected on a geographic basis in relation to the national population distribution. Within each practice, 250 patients aged 45-64 years were selected at random. Data relating to 19 diagnoses, six surgical procedures and 40 repeat prescription drugs were extracted from the computer records of these patients and compared with information held on patients' paper records and supplied by patients in response to a postal questionnaire. The completeness and accuracy of computer entries were assessed in terms of sensitivity and positive predictive value, respectively., Results: For the 5567 patients for whom all three sources of data (validated computer records, paper records and questionnaire responses) were available, sensitivity (completeness) of morbidity recording had median values of 0.67 for diagnoses, 0.93 for surgical procedures and 0.75 over all conditions examined. Practices varied both in the completeness of recording of each condition and in their overall performance. The predictive value (accuracy) of morbidity data was uniformly high for all conditions examined (median 1.00). For repeat prescription drugs, recording on GPASS was both complete and accurate., Conclusion: The recording of morbidity data on GPASS for 45-64-year-old patients in a selected group of 41 highly-computerized practices is about 75% complete and highly accurate. For national morbidity studies, it seems likely that amalgamated data from the best GPASS practices will be as complete and accurate as the morbidity statistics currently derived from hospital-based activities in Scotland.

Objective: To identify how computerised practices using Gpass software (General Practice Administration System for Scotland), currently implement the new health promotion regulations., Design: Postal questionnaire to all Gpass practices in Scotland. Data were gathered on types and methods of recording health promotion data, Read code selection, health education given and intended methods of data analysis. Questionnaire results were compared with data from an Electronic Questionnaire analysing actual data recorded on practice computers., Results: Overall response rate: 64.6%, 94.8% of the responding practices have been approved for health promotion band three. Most practices (94.5%) use their computer for data collection, 63.6% of practices use a manual data capture form and 28.8% use computer data capture methods. Methods of collecting patient data and selection of Read codes for computer data entry are variable. Most practices use one method of data collection; a significant minority use multiple methods or more than one Read code to record the same item. The recording of health promotion on computer has increased greatly since the introduction of the new regulations: the current levels of recording are alcohol history (26.3%), blood pressure reading (57.6%), smoking (35.4%), exercise (7.1%), weight (21.4%) and height (16.4%). Most practices (94.3%) intend using Gpass for data analysis., Conclusion: Methods of collecting and recording health promotion data differ greatly between practices, with variable standardisation of health promotion codes and differing use of appropriate elements of the Gpass software.

Objective: To compare three sets of dietary guidelines for the treatment of non-insulin-dependent diabetes (NIDDM) in free-living individuals and to observe the effects on metabolic control over an 18-month period., Research Design and Methods: Seventy volunteer subjects with NIDDM were randomly assigned to one of three diets, a weight-management diet, a high-carbohydrate/fiber diet, or a modified-lipid diet and followed for 18 months. Nutrient intakes, weight, blood lipids, and glycemic control were measured., Results: In all diet groups, glycated hemoglobin (HbA1) fell significantly before diet intervention began, remaining lower throughout the study and at follow-up 9 months later. Low-density lipoprotein (LDL) cholesterol showed a sustained fall in all groups after diet intervention. Apart from transient changes in high-density lipoprotein (HDL) cholesterol and triglyceride (TG) in the diet groups with the higher carbohydrate intake, no lasting differences were found between the three diet groups., Conclusions: In the long term, there were few differences in the outcome of the three dietary prescriptions. Even with intensive instruction, participants found it difficult to meet recommended nutrient intakes; however, specific dietary advice did result in an improvement in LDL cholesterol. Adverse changes in HDL cholesterol and TG because of diet intervention were transient. The significant improvement in glycemic control during the recruitment phase may have been the result of participants' previous dietary knowledge and the increased attention that they received during the intervention.

The electronic questionnaire has been developed as a means of collecting data held on computers in Scottish General Practices using the standard national general practice computer system (GPASS). In 1989, data were gathered from 251 computerised Scottish practices using a floppy disc based interrogation program, amalgamated and then analysed. The results of this study are presented and examined in three separate ways: by region, by date of initial computerisation, and by list size per general practitioner (GP).