James S. McLay

Learning curves, taking instructions, and patient safety: using a theoretical domains framework in an interview study to investigate prescribing errors among trainee doctors

BackgroundPrescribing errors are a major source of morbidity and mortality and represent a significant patient safety concern. Evidence suggests that trainee doctors are responsible for most prescribing errors. Understanding the factors that influence prescribing behavior may lead to effective interventions to reduce errors. Existing investigations of prescribing errors have been based on Human Error Theory but not on other relevant behavioral theories. The aim of this study was to apply a broad theory-based approach using the Theoretical Domains Framework (TDF) to investigate prescribing in the hospital context among a sample of trainee doctors.MethodSemistructured interviews, based on 12 theoretical domains, were conducted with 22 trainee doctors to explore views, opinions, and experiences of prescribing and prescribing errors. Content analysis was conducted, followed by applying relevance criteria and a novel stage of critical appraisal, to identify which theoretical domains could be targeted in interventions to improve prescribing.ResultsSeven theoretical domains met the criteria of relevance: “social professional role and identity,” “environmental context and resources,” “social influences,” “knowledge,” “skills,” “memory, attention, and decision making,” and “behavioral regulation.” From critical appraisal of the interview data, “beliefs about consequences” and “beliefs about capabilities” were also identified as potentially important domains. Interrelationships between domains were evident. Additionally, the data supported theoretical elaboration of the domain behavioral regulation.ConclusionsIn this investigation of hospital-based prescribing, participants’ attributions about causes of errors were used to identify domains that could be targeted in interventions to improve prescribing. In a departure from previous TDF practice, critical appraisal was used to identify additional domains that should also be targeted, despite participants’ perceptions that they were not relevant to prescribing errors. These were beliefs about consequences and beliefs about capabilities. Specifically, in the light of the documented high error rate, beliefs that prescribing errors were not likely to have consequences for patients and that trainee doctors are capable of prescribing without error should also be targeted in an intervention. This study is the first to suggest critical appraisal for domain identification and to use interview data to propose theoretical elaborations and interrelationships between domains.

Perceived causes of prescribing errors by junior doctors in hospital inpatients: a study from the PROTECT programme

Introduction Prescribing errors are a major cause of patient safety incidents. Understanding the underlying factors is essential in developing interventions to address this problem. This study aimed to investigate the perceived causes of prescribing errors among foundation (junior) doctors in Scotland. Methods In eight Scottish hospitals, data on prescribing errors were collected by ward pharmacists over a 14-month period. Foundation doctors responsible for making a prescribing error were interviewed about the perceived causes. Interview transcripts were analysed using content analysis and categorised into themes previously identified under Reasons Model of Accident Causation and Human Error. Results 40 prescribers were interviewed about 100 specific errors. Multiple perceived causes for all types of error were identified and were categorised into five categories of error-producing conditions, (environment, team, individual, task and patient factors). Work environment was identified as an important aspect by all doctors, especially workload and time pressures. Team factors included multiple individuals and teams involved with a patient, poor communication, poor medicines reconciliation and documentation and following incorrect instructions from other members of the team. A further team factor was the assumption that another member of the team would identify any errors made. The most frequently noted individual factors were lack of personal knowledge and experience. The main task factor identified was poor availability of drug information at admission and the most frequently stated patient factor was complexity. Conclusions This study has emphasised the complex nature of prescribing errors, and the wide range of error-producing conditions within hospitals including the work environment, team, task, individual and patient. Further work is now needed to develop and assess interventions that address these possible causes in order to reduce prescribing error rates.

Cytokine-Stimulated Nitric Oxide Production in the Human Renal Proximal Tubule and Its Modulation by Natriuretic Peptides: A Novel Immunomodulatory Mechanism?

Although the importance of the human kidney in a variety of disease states is well recognised, the exact mechanisms involved remain unclear. Animal disease models suggest that while high local concentrations of nitric oxide (NO) may play a key role in the initiation and progression of renal disease, low levels may also be essential for normal renal function and cell protection, possibly explaining the variable reports of both beneficial and detrimental responses of renal disease models following NO inhibition. NO has both physiological and pathological roles and clearly a balance between these two primary roles is likely to prevail leading to the conclusion that partial rather than total inhibition of NO production may be beneficial. Despite increasing evidence for the role of NO from animal disease models, little is known of the role of NO and potential modulators within the human kidney. In this review we describe three series of studies during which we examined the ability of primary cultures of human proximal tubular cells to produce NO in response to inflammatory cytokines and the possible role of potential modulators such as the natriuretic peptides. Following challenge with the combination of inflammatory cytokines IL-1β, TNF-α, and IFN-γ, such cultures exhibit a time-dependent increase in inducible NO synthetase induction and corresponding NO production, an effect which was inhibited by L-NMMA. In the second series of studies we demonstrated that increasing concentrations of atrial natriuretic factor (ANF) or C(4–23)ANF could stimulate a time- and concentration-dependent increase in nitric oxide production which was again abolished by L-NMMA. These results suggested that ANF acting at the natriuretic peptide receptor C could stimulate nitric oxide production in human proximal tubular cells. In the final series of studies we demonstrated that pro-inflammatory cytokine-induced nitric oxide production could be inhibited by ANF, brain natriuretic peptide, C-type natriuretic peptide or C(4–23)ANF. The actions of the natriuretic peptides and C(4–23)ANF was to return pro-inflammatory nitric oxide production to those observed when human proximal tubular cells were incubated with ANF alone indicating that this inhibition was mediated via the natriuretic peptide receptor C. The function of NO in the kidney is unclear but undoubtedly it has both beneficial and detrimental actions which in health remain in balance. However, when the kidney is subjected to an immune challenge, high cytotoxic levels of NO are produced locally and appear to be responsible for local damage, unfortunately total inhibition of NO production during such disease states does not always result in benefit. Clearly total abolition of an NO response removes important integral protective actions such as vasodilation. In the ideal situation, treatment of disease processes related to NO excess would involve the inhibition of these high local levels while still protecting vital dependent mechanisms. We believe that the NO natriuretic peptide interaction, which we have reported in this review, places ANF in a unique position of being able to maintain the essential or protective actions of NO while inhibiting potentially cytotoxic or detrimental effects.

Atrial natriuretic factor modulates nitric oxide production : an ANF-C receptor-mediated effect

Objectives: To investigate the possible immunomodulatory and regulatory functions of atrial natriuretic factor (ANF) and the natriuretic peptide C (NPR-C) receptor in the control of cytokine-stimulated nitric oxide production in primary cultures of human proximal tubular cells. Methods: Freshly prepared human proximal tubular cells were seeded on plastic plates and allowed to reach confluence. The confluent cells were then incubated with ANF or cycliC(4_23)ANF (c(4_23)ANF) alone, or preincubated with ANF or C(4_23)ANF before incubation with the nitric oxide-stimulating combination of cytokines interleukin-1|3 (10u/ml), tumour necrosis factor-cc (10ng/ml) and interferon-y (100 u/ml). Results: In the present series of experiments we have found that incubation of primary cultures of human proximal tubular cells with ANF or C(4_23)ANF stimulates nitric oxide production dose-dependently. Paradoxically, ANF acting via the NPR-C receptor also inhibits cytokine activation of the enzyme-inducible nitric oxide synthase via a cyclic GMP-independent mechanism. Both of these effects were reproduced by the NPR-C receptor-specific ligand cIn the present series of experiments we have found that incubatio4_23)ANF. Conclusions: These findings represent novel actions of ANF mediated via the NPR-C receptor. The results also provide a simple model system in which to study the subcellular mechanisms of NPR-C receptor activation.

A Comparative Review of the Adverse Effects of Calcium Antagonists

SummaryA large number of drugs within the 3 currently available classes of calcium antagonists are in common medical use for the treatment of hypertension and ischaemic heart disease. The reported adverse effect profile for each of these drugs varies, but tends to hold true to drug class and are typified by the adverse reactions reported for nifedipine and amlodipine (dihydropyridines), diltiazem (benzothiazepines) and verapamil (phenylalkylamines). Minor adverse effects such as flushing, headache, ankle oedema, palpitations and constipation are not uncommon and frequently require the cessation of treatment. Of greater concern affecting the wide and common first-line use of calcium antagonists is the as-yet unresolved issue of a reportedly greater risk of myocardial infarction and death following the use of short-acting nifedipine in patients with a history of hypertension, myocardial infarction or angina. Until this issue is fully resolved, it would seem prudent to limit the use of this agent in ‘at-risk’ patients and to await the results of further prospective studies before a final conclusion can be made.

A prospective questionnaire assessment of attitudes and experiences of off label prescribing among hospital based paediatricians

Objective: To assess current attitudes of hospital based paediatricians to off label prescribing, and the performance of clinical trials in children. Design: A prospective, questionnaire based study. Setting: 257 hospital based consultants and specialist registrars in paediatric practice in Scotland during 2003–2004. Results: A 25 item questionnaire was sent to 257 hospital based paediatricians and 151 (59%) were returned completed. Over 90% of responders were familiar with the concept of, and knowingly prescribed, off label drugs; 55% of responders stated that such prescribing disadvantaged children, and 47% expressed concerns about the efficacy of off label medicines. Although 70% of responders expressed concerns about safety, only 17% had observed an adverse event, and 47% a treatment failure, while 69% did not obtain informed consent or tell parents they were prescribing off label, and 67% did not inform the family’s general practitioner. Many respondents did not believe it was necessary to carry out clinical trials in children for new (46%) or generic (64%) medicines. However, 52% of respondents stated that they would be willing to undertake clinical studies and recruit their own patients (61%) or children (73%) to take part in such studies. Conclusions: Among Scottish paediatricians there is concern about off label prescribing, although the majority do not consider it necessary to inform parents or GP colleagues. The need for clinical trials in children was recognised but there was a less than wholehearted acceptance of the need for such studies, at variance with the current drive to promote clinical trials in this age group.

Complementary and alternative medicines use by Scottish women with breast cancer. What, why and the potential for drug interactions?

BackgroundDespite the increased use of complementary and alternative medicine (CAM) by breast cancer patients, there is little published information regarding CAM use in the Scottish breast cancer population.MethodsA questionnaire comprising five sections—demographics; perceived health status, prescribed medicines; use, indications, satisfaction and expenditure on CAMs; attitudes towards and factors associated with CAM use; and attitudinal statements—was issued to patients attending the Aberdeen Breast Clinic.ResultsA total of 453 questionnaires were distributed and 360 (79.5%) returned. Respondents were prescribed a mean of 3.2 medicines (95% CI 2.83–3.47). With regard to CAM use, 33.1% of respondents reported current use, 36.4% prior use, and 30.6% reported never having used CAMs. The key indications for use were general well being, boosting immune system and cancer prophylaxis, with high levels of satisfaction reported. The strongest association for CAM use was use by friends and family and higher educational attainment (p < 0.001). Supplements with estrogenic activity, such as soya or red clover, were taken by 29% of respondents. Herbs (echinacea, pomegranate, peppermint, chamomile, grapefruit, garlic, ginseng) that have the potential to interact with adjuvant endocrine therapies (tamoxifen, anastrazole, letrozole, exemestane) were being taken by 38% of treated patients.ConclusionThe level of CAM use by Scottish breast cancer patients is similar to that reported from other countries, although there are marked differences in the type, nature and frequency of specific CAM therapies. Higher patient education level and use by family and friends were significantly associated with CAM use. The high level of use of potentially disease modifying or interacting herb supplements may be of concern.

Maternal vitamin D and E intakes during pregnancy are associated with asthma in children

Are maternal vitamin D and E intakes during pregnancy associated with asthma in 10-year-old children? In a longitudinal study of 1924 children born to women recruited during pregnancy, maternal vitamin D intake during pregnancy was assessed by the Food Frequency Questionnaire (FFQ) and vitamin E by FFQ and plasma α-tocopherol; respiratory questionnaires were completed for the 10-year-old children. Their treatment for asthma was also ascertained using administrative data. Longitudinal analyses included data collected at 1, 2, 5 and 10 years. Symptom data were available for 934 (49%) children and use of asthma medication for 1748 (91%). In the children maternal vitamin D intake during pregnancy was negatively associated with doctor-diagnosed asthma at 10 years of age (OR per intake quintile 0.86, 95% CI 0.74–0.99) and over the first 10 years (hazard ratio 0.90, 95% CI 0.81–1.00). Maternal plasma α-tocopherol at 11 weeks gestation was negatively associated with children receiving asthma treatment (OR per standard deviation increase 0.52, 95% CI 0.31–0.87). Maternal vitamin E intake was negatively associated with doctor-diagnosed asthma (OR 0.89, 95% CI 0.81–0.99) in the first 10 years. Low maternal vitamin D and E intakes during pregnancy are associated with increased risk of children developing asthma in the first 10 years of life. These associations may have significant public health implications. Children born to women with low vitamin D and E intakes during pregnancy are more likely to develop asthma by age 10 http://ow.ly/CmDo8

The Potential for Interaction between Warfarin and Coprescribed Medication : A Retrospective Study in Primary Care

Background and objectiveWarfarin is commonly involved in drug-related hospital admissions. The drug is most commonly prescribed to elderly patients in whom polypharmacy is common and, when administered in combination with other drugs such as NSAIDs, aspirin (acetylsalicylic acid) or macrolide antibacterials, is associated with increased bleeding risk. The aim of this study was to investigate the prevalence of prescriptions that might give rise to clinically relevant drug-drug interactions in a warfarinized population.MethodsPrimary care prescribing of warfarin and potentially interacting medicines was assessed between 1 April 2005 and 31 March 2006 using computerized prescribing data retrieved from 321 primary care practices in Scotland.ResultsA total of 17 861 registered patients were prescribed warfarin in the study year, of whom 68% (n = 12 107) were concomitantly issued with a prescription for at least one potentially interacting medicine. For short-term use, ‘one-off’ prescriptions for antibacterials (sulfonamides, ciprofloxacin, and macrolides), nonselective NSAIDs and antithrombotics (fibrinolytics) were the most frequently prescribed drug groups with potential for interaction, being prescribed to 12.7%, 5.3%, and 1.4% of warfarinized patients, respectively. Macrolide antibacterials were prescribed in significantly fewer warfaranized patients than standardized population (3.84% vs 4.41%; p < 0.001). For long-term use, nonselective NSAIDs and antithrombotics were the most frequently prescribed drug groups, being prescribed to 21.0% and 21.1% of warfarinized patients, respectively. When compared with a standardized population, NSAIDs and antithrombotics were prescribed to a significantly smaller proportion of the warfarin population, whereas selective cyclo-oxygenase 2 inhibitors were prescribed to a significantly greater proportion. Nevertheless for the whole warfarinized population 26.3% were prescribed nonselective NSAIDs and 22.5% antithrombotic agents.ConclusionsThe lower ‘one off’ use of macrolide antibacterials and long-term use of antithrombotics and NSAIDs in warfarinized patients observed in this study might suggest awareness among general practitioners of the increased risks for bleeding associated with concomitant use of these agents with warfarin therapy. However, despite this, the majority of warfarinized patients in this study were issued with a repeat prescription for at least one potentially interacting medicine.

Drug Treatment of Hypertension Complicating Diabetes Mellitus

Hypertension and diabetes mellitus are both common conditions associated with a high morbidity and mortality. When the two conditions occur together, as they do in 50% of diabetic individuals, the result is a 7.2-fold increase in mortality. If hypertension occurs in association with diabetes mellitus and diabetic nephropathy, mortality rises to 37-fold above that of a healthy population.Despite the increase in incidence of nephropathy, cardiovascular disease remains the major cause of death in diabetic individuals. Therapy should therefore take into consideration the results of large, placebo-controlled trials which have shown reduction in cardiovascular morbidity and mortality as a result of active treatment. Although studies with the newer antihypertensive agents such as calcium antagonists and angiotensin converting enzyme (ACE) inhibitors are ongoing, only diuretics and β-adrenoceptor antagonists have been clearly shown to reduce cardiovascular risk.Despite concerns regarding adverse metabolic effects and loss of hypoglycaemic awareness, β-blockers and diuretics do have a role in the management of diabetic patients. While it is clear that ACE inhibitors reduce the progression of diabetic nephropathy, evidence suggests that diuretics may be just as effective. However, unlike diuretics or β-blockers, ACE inhibitors have no proven benefit in the prevention of stroke or myocardial infarction. Despite the claims of metabolic neutrality made for many antihypertensive agents there appears to be no advantage in their use in the majority of hypertensive diabetic patients, except where there exist specific contraindications to established therapies.