Mark Mullee

Frequency and impact of nonadherence to immunosuppressants after renal transplantation: A systematic review

Nonadherence to immunosuppressants is recognized to occur after renal transplantation, but the size of its impact on transplant survival is not known. A systematic literature search identified 325 studies (in 324 articles) published from 1980 to 2001 reporting the frequency and impact of nonadherence in adult renal transplant recipients. Thirty-six studies meeting the inclusion criteria for further review were grouped into cross-sectional and cohort studies and case series. Meta-analysis was used to estimate the size of the impact of nonadherence on graft failure. Only two studies measured adherence using electronic monitoring, which is currently thought to be the most accurate measure. Cross-sectional studies (n=15) tended to rely on self-report questionnaires, but these were poorly described; a median (interquartile range) of 22% (18%–26%) of recipients were nonadherent. Cohort studies (n=10) indicated that nonadherence contributes substantially to graft loss; a median (interquartile range) of 36% (14%–65%) of graft losses were associated with prior nonadherence. Meta-analysis of these studies showed that the odds of graft failure increased sevenfold (95% confidence interval, 4%–12%) in nonadherent subjects compared with adherent subjects. Standardized methods of assessing adherence in clinical populations need to be developed, and future studies should attempt to identify the level of adherence that increases the risk of graft failure. However, this review shows nonadherence to be common and to have a large impact on transplant survival. Therefore, significant improvements in graft survival could be expected from effective interventions to improve adherence.

Safety and effectiveness of nurse telephone consultation in out of hours primary care: randomised controlled trial

Abstract Objective To determine the safety and effectiveness of nurse telephone consultation in out of hours primary care by investigating adverse events and the management of calls. Design Block randomised controlled trial over a year of 156 matched pairs of days and weekends in 26 blocks. One of each matched pair was randomised to receive the intervention. Setting One 55 member general practice cooperative serving 97 000 registered patients in Wiltshire. Subjects All patients contacting the out of hours service or about whom contact was made during specified times over the trial year. Intervention A nurse telephone consultation service integrated within a general practice cooperative. The out of hours period was 615 pm to 1115 pm from Monday to Friday, 1100 am to 1115 pm on Saturday, and 800 am to 1115 pm on Sunday. Experienced and specially trained nurses received, assessed, and managed calls from patients or their carers. Management options included telephone advice; referral to the general practitioner on duty (for telephone advice, an appointment at a primary care centre, or a home visit); referral to the emergency service or advice to attend accident and emergency. Calls were managed with the help of decision support software. Main outcome measures Deaths within seven days of a contact with the out of hours service; emergency hospital admissions within 24 hours and within three days of contact; attendance at accident and emergency within three days of a contact; number and management of calls in each arm of the trial. Results 14 492 calls were received during the specified times in the trial year (7308 in the control arm and 7184 in the intervention arm) concerning 10 134 patients (10.4% of the registered population). There were no substantial differences in the age and sex of patients in the intervention and control groups, though male patients were underrepresented overall. Reasons for calling the service were consistent with previous studies. Nurses managed 49.8% of calls during intervention periods without referral to a general practitioner. A 69% reduction in telephone advice from a general practitioner, together with a 38% reduction in patient attendance at primary care centres and a 23% reduction in home visits was observed during intervention periods. Statistical equivalence was observed in the number of deaths within seven days, in the number of emergency hospital admissions, and in the number of attendances at accident and emergency departments. Conclusions Nurse telephone consultation produced substantial changes in call management, reducing overall workload of general practitioners by 50% while allowing callers faster access to health information and advice. It was not associated with an increase in the number of adverse events. This model of out of hours primary care is safe and effective.

A population-based study of the incidence and outcomes of diagnosed chronic kidney disease

BACKGROUND This study aims to determine the incidence rate and prognosis of detected chronic kidney disease (CKD) in a defined population. METHODS This is a retrospective cohort study of all new cases of CKD from Southampton and South-West Hampshire Health Authority (population base, 405,000) determined by a persistently increased serum creatinine (SCr) level (>or=1.7 mg/dL [>or=150 micromol/L] for 6 months) identified from chemical pathology records. Follow-up was for a mean of 5.5 years for survival, cause of death, and acceptance to renal replacement therapy (RRT). RESULTS The annual incidence rate of detected CKD was 1,701 per million population (pmp; 95% confidence interval [CI], 1,613 to 1,793) and 1,071 pmp (95% CI, 1,001 to 1,147) in those younger than 80 years. There was a steep age gradient; median age was 77 years. The man-woman rate ratio was 1.6 (95% CI, 1.4 to 1.8), with a male excess in all age groups older than 40 years. Incidence increased in areas with greater socioeconomic deprivation. Median survival was 35 months. Age, SCr level, and deprivation index were all significantly associated with survival. Standardized mortality ratios were 36-fold in those aged 16 to 49 years, 12-fold in those aged 50 to 64 years, and more than 2-fold in those older than 65 years. Cardiovascular disease (CVD) was the most common cause of death (46%). Only 4% of patients were accepted to RRT. CONCLUSION The incidence of diagnosed CKD is common, especially in the elderly, and is greater in more deprived areas. Prognosis is poor, with CVD prominent. More research is needed to assess the effectiveness and costs of increasing referral to nephrologists of patients with CKD.

Evaluation of peak flow and symptoms only self management plans for control of asthma in general practice.

OBJECTIVE--To compare a peak flow self management plan for asthma with a symptoms only plan. DESIGN--Randomisation to one of the self management plans and follow up for a year. SETTING--Four partner, rural training practice in Norfolk. SUBJECTS--115 Patients (46 children and 69 adults) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic. MAIN OUTCOME MEASURES--The number of doctor consultations, courses of oral steroids, and short term nebulised salbutamol treatments and the number of patients who required doctor consultations, courses of oral steroids, and short term nebulised salbutamol. RESULTS--Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups. The results were similar for children and adults. The proportions of patients requiring a doctor consultation fell from 98% (50/51) to 66% (34/51) in the peak flow group and from 97% (62/64) to 53% (34/64) in the symptoms only group and the proportions requiring oral steroids from 73% (34/46) to 47% (21/46) and 52% (31/60) to 12% (7/60). The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group. CONCLUSIONS--The peak flow meter was not the crucial ingredient in the improved illness of the two groups. Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma. Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care.

Explaining the rise in antidepressant prescribing: a descriptive study using the general practice research database

Objective To explore the reasons behind the recent increase in antidepressant prescribing in the United Kingdom. Design Detailed retrospective analysis of data on general practitioner consultations and antidepressant prescribing. Data source Data were obtained from the general practice research database, which contains linked anonymised records of over 3 million patients registered in the UK. Data were extracted for all new incident cases of depression between 1993 and 2005. Review methods Detailed analysis of general practitioner consultations and antidepressant prescribing was restricted to 170 practices that were contributing data for the full duration of the study. Results In total, 189 851 people within the general practice research database experienced their first episode of depression between 1993 and 2005, of whom 150 825 (79.4%) received a prescription for antidepressants in the first year of diagnosis. This proportion remained stable across all the years examined. The incidence of new cases of depression rose in young women but fell slightly in other groups such that overall incidence increased then declined slightly (men: 7.83 cases per 1000 patient years in 1993 to 5.97 in 2005, women: 15.83 cases per 1000 patient years in 1993 to 10.06 in 2005). Antidepressant prescribing nearly doubled during the study period—the average number of prescriptions issued per patient increased from 2.8 in 1993 to 5.6 in 2004. The majority of antidepressant prescriptions were given as long term treatment or as intermittent treatment to patients with multiple episodes of depression. Conclusions The rise in antidepressant prescribing is mainly explained by small changes in the proportion of patients receiving long term treatment. Previous clinical guidelines have focused on antidepressant initiation and appropriate targeting of antidepressants. To address the costly rise in antidepressant prescribing, future research and guidance needs to concentrate on appropriate long term prescribing for depression and regular review of medication.

Effects of internet-based training on antibiotic prescribing rates for acute respiratory-tract infections: a multinational, cluster, randomised, factorial, controlled trial

Summary Background High-volume prescribing of antibiotics in primary care is a major driver of antibiotic resistance. Education of physicians and patients can lower prescribing levels, but it frequently relies on highly trained staff. We assessed whether internet-based training methods could alter prescribing practices in multiple health-care systems. Methods After a baseline audit in October to December, 2010, primary-care practices in six European countries were cluster randomised to usual care, training in the use of a C-reactive protein (CRP) test at point of care, in enhanced communication skills, or in both CRP and enhanced communication. Patients were recruited from February to May, 2011. This trial is registered, number ISRCTN99871214. Results The baseline audit, done in 259 practices, provided data for 6771 patients with lower-respiratory-tract infections (3742 [55·3%]) and upper-respiratory-tract infections (1416 [20·9%]), of whom 5355 (79·1%) were prescribed antibiotics. After randomisation, 246 practices were included and 4264 patients were recruited. The antibiotic prescribing rate was lower with CRP training than without (33% vs 48%, adjusted risk ratio 0·54, 95% CI 0·42–0·69) and with enhanced-communication training than without (36% vs 45%, 0·69, 0·54–0·87). The combined intervention was associated with the greatest reduction in prescribing rate (CRP risk ratio 0·53, 95% CI 0·36–0·74, p<0·0001; enhanced communication 0·68, 0·50–0·89, p=0·003; combined 0·38, 0·25–0·55, p<0·0001). Interpretation Internet training achieved important reductions in antibiotic prescribing for respiratory-tract infections across language and cultural boundaries. Funding European Commission Framework Programme 6, National Institute for Health Research, Research Foundation Flanders.

Prognostic value of the Framingham cardiovascular risk equation and the UKPDS risk engine for coronary heart disease in newly diagnosed Type 2 diabetes: results from a United Kingdom study

Aims  To determine the prognostic value of the Framingham equation and the United Kingdom Prospective Diabetes Study (UKPDS) risk engine in patients with newly diagnosed Type 2 diabetes.

The Distribution and Severity of Diabetic Foot Disease: a Community Study with Comparison to a Non‐diabetic Group

A surveillance programme was undertaken to identify all diabetic patients with foot disease in a defined population with the same age and sex structure as that of the UK. Of 1150 diabetic patients identified, 1077 were reviewed either at home or in hospital. The presence of foot deformity, amputation, and foot ulceration was determined. The site, depth, and duration of ulcers were recorded and any previous ulceration noted. All feet with ulcers were X‐rayed. A non‐diabetic comparison group of 480 age‐ and sex‐matched individuals were also examined by the same observer. The prevalence of past or present foot ulceration was 7.4 (95% CI 5.8–9.0)% in diabetic patients and 2.5 (95% CI 1.1–3.9)% in the non‐diabetic group, yielding an odds ratio of 2.94 (95% CI 1.58–5.48) (p < 0.001) for the occurrence of foot ulceration in diabetic patients. Of the ulcers found on examination, 39.4% were neuropathic, 24.2% were vascular, and 36.4% were mixed. Multiple logistic regression analysis of selected variables revealed that duration of diabetes, absent light touch, impaired pain perception, absent dorsalis pedis pulse, and the presence of any retinopathy were significant predictors of the presence of foot ulcers. The prevalence of amputation in diabetic patients was 1.3 (95% CI 0.6–2.0)%, but there were no amputations in the non‐diabetic group.

Microalbuminuria in Diabetes: A Population Study of the Prevalence and an Assessment of Three Screening Tests

A single observer reviewed 842 of the 917 known diabetic patients registered with 40 GPs in the Poole area. A midstream urine specimen was tested for proteinuria using Albustix (Ames) and cultured to detect bacterial infection. After the first 3 months of the survey, the aliquot of this specimen was frozen for later determination of the random albumin/creatinine ratio (R‐Alb/Creat). Patients were requested to submit a timed overnight urine collection for estimation of urinary albumin excretion rate (AER).

Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial

Objective To assess the impact of different management strategies in urinary tract infections. Design Randomised controlled trial. Setting Primary care. Participants 309 non-pregnant women aged 18-70 presenting with suspected urinary tract infection. Intervention Patients were randomised to five management approaches: empirical antibiotics; empirical delayed (by 48 hours) antibiotics; or targeted antibiotics based on a symptom score (two or more of urine cloudiness, urine smell, nocturia, or dysuria), a dipstick result (nitrite or both leucocytes and blood), or a positive result on midstream urine analysis. Self help advice was controlled in each group. Main outcome measures Symptom severity (days 2 to 4) and duration, and use of antibiotics. Results Patients had 3.5 days of moderately bad symptoms if they took antibiotics immediately. There were no significant differences in duration or severity of symptoms (mean frequency of symptoms on a 0 to 6 scale: immediate antibiotics 2.15, midstream urine 2.08, dipstick 1.74, symptom score 1.77, delayed antibiotics 2.11; likelihood ratio test for the five groups P=0.177). There were differences in antibiotic use (immediate antibiotics 97%, midstream urine 81%, dipstick 80%, symptom score 90%, delayed antibiotics 77%; P=0.011) and in sending midstream urine samples (immediate antibiotics 23%, midstream urine 89%, dipstick 36%, symptom score 33%, delayed antibiotics 15%; P<0.001). Patients who waited at least 48 hours to start taking antibiotics reconsulted less (hazard ratio 0.57 (95% confidence interval 0.36 to 0.89), P=0.014) but on average had symptoms for 37% longer than those taking immediate antibiotics (incident rate ratio 1.37 (1.11 to 1.68), P=0.003), particularly the midstream urine group (73% longer, 22% to 140%; none of the other groups had more than 22% longer duration). Conclusion All management strategies achieve similar symptom control. There is no advantage in routinely sending midstream urine samples for testing, and antibiotics targeted with dipstick tests with a delayed prescription as backup, or empirical delayed prescription, can help to reduce antibiotic use. Study registration National Research Register N0484094184 ISRCTN: 03525333.