Selective decrease in consultations and antibiotic prescribing for acute respiratory tract infections in UK primary care up to 2006.

BACKGROUND: The aim of this study was to estimate trends in primary care consultations and antibiotic prescribing for acute respiratory tract infections (RTIs) in the UK from 1997 to 2006. METHODS: Data were analysed for 100,000 subjects registered with 78 family practices in the UK General Practice Research Database; the numbers of consultations for RTI and associated antibiotic prescriptions were enumerated. RESULTS: The consultation rate for RTI declined in females from 442.2 per 1000 registered patients in 1997 to 330.9 in 2006, and in males from 318.5 to 249.0. The rate of consultations for colds, rhinitis and upper respiratory tract infection (URTI) declined by 4.2 (95% CI 2.3-6.1) per 1000 per year in females and by 3.6 (2.3-4.8) in males. The rate of antibiotic prescribing for RTI was higher in females and declined by 8.5 (2.0-15.1) per 1000 in females and 6.7 (2.7-10.8) in males. For colds, rhinitis and URTI, the proportion of consultations with antibiotics was prescribed declined by 1.7% per year in females and 1.8% in males. CONCLUSIONS: Decreasing frequency of consultation and antibiotic prescription for colds, rhinitis and 'URTI' continues to drive a reduction in the rate of antibiotic utilization for RTIs.

Evaluation of newborn sickle cell screening programme in England: 2010-2016.

OBJECTIVE: To evaluate England's NHS newborn sickle cell screening programme performance in children up to the age of 5 years. DESIGN: Cohort of resident infants with sickle cell disease (SCD) born between 1 September 2010 and 31 August 2015 and followed until August 2016. PARTICIPANTS: 1317 infants with SCD were notified to the study from all centres in England and 1313 (99%) were followed up. INTERVENTIONS: Early enrolment in clinical follow-up, parental education and routine penicillin prophylaxis. MAIN OUTCOME MEASURES: Age seen by a specialist clinician, age at prescription of penicillin prophylaxis and mortality. RESULTS: All but two resident cases of SCD were identified through screening; one baby was enrolled in care after prenatal diagnosis; one baby whose parents refused newborn screening presented symptomatically. There were 1054/1313 (80.3%, 95% CI 78% to 82.4%) SCD cases seen by a specialist by 3 months of age and 1273/1313 (97%, 95% CI 95.9% to 97.8%) by 6 months. The percentage seen by 3 months increased from 77% in 2010 to 85.4% in 2015. 1038/1292 (80.3%, 95% CI 78.1% to 82.5%) were prescribed penicillin by 3 months of age and 1257/1292 (97.3%, 95% CI 96.3% to 98.1%) by 6 months. There were three SCD deaths <5 years caused by invasive pneumococcal disease (IPD) sensitive to penicillin. CONCLUSION: The SCD screening programme is effective at detecting affected infants. Enrolment into specialist care is timely but below the programme standards. Mortality is reducing but adherence to antibiotic prophylaxis remains important for IPD serotypes not in the current vaccine schedule.

No association between immunization and Guillain-Barré syndrome in the United Kingdom, 1992 to 2000.

BACKGROUND: Our goal was to determine whether immunization is associated with the incidence of Guillain-Barré syndrome (GBS). METHODS: We analyzed data for all patients registered with 253 general practices in the United Kingdom General Practice Research Database from 1992 to 2000, with a mean of 1.8 million registered patients. We identified new occurrences of GBS and estimated age- and sex-specific and age-standardized incidence rates. We then determined whether the date of diagnosis was made within 42 days of any immunization and estimated the relative risk of diagnosis following immunization after adjusting for age and sex. RESULTS: There were 228 incident cases of GBS, including 107 women and 121 men. The age-standardized incidence rate per 100 000 person-years was 1.22 (95% confidence interval [CI], 0.98-1.46) in women and 1.45 (95% CI, 1.19-1.72) in men. Age-specific incidence rates per 100 000 person-years were highest in men aged 65 to 74 years (3.86; 95% CI, 2.50-5.70) and women aged 75 to 84 years (2.54; 95% CI, 1.39-4.27). There were 7 cases (3.1%) in which the onset occurred within 42 days of any immunization; 3 of the 7 cases occurred after influenza immunization. There were 221 cases (97.0%) that were not associated with immunization. The adjusted relative risk during the 42 days after immunization was 1.03 (95% CI, 0.48-2.18; P = .94). CONCLUSIONS: There is either minimal or no risk of GBS associated with routine immunization practice in the United Kingdom. Obtaining a precise estimate of any potential risk associated with an individual vaccine would require a study with more GBS cases.

Increased utilization of primary care 5 years before diagnosis of type 2 diabetes: a matched cohort study.

OBJECTIVE: To determine whether case subjects who were later diagnosed with type 2 diabetes utilized primary care differently from control subjects who remained free from diabetes. RESEARCH DESIGN AND METHODS: We conducted a matched cohort study using the U.K. General Practice Research Database. Case subjects were aged 30-89 years, diagnosed with diabetes, and later prescribed oral hypoglycemic drugs between 1997 and 2000. Control subjects, who were matched for age, sex, and general practice, were not diagnosed with diabetes and not treated with oral hypoglycemic drugs or insulin. RESULTS: Data were analyzed for 5,158 case subjects (2,492 women and 2,666 men) and their matched control subjects with a mean age of 63 years. Five years before the date of diagnosis, case subjects consulted more frequently than control subjects (rate ratio [RR] 1.26 [95% CI 1.20-1.33]) and received more prescription items (1.44 [1.36-1.53]). Consultations were increased for a wide range of conditions. The cumulative 5-year prevalence of diagnoses of hypertension or treatment, hyperlipidemia or treatment, obesity, or coronary heart disease or stroke was 66.1% in case subjects and 45.9% in control subjects (1.44 [1.40-1.49]). A medical diagnosis of hyperglycemia or impaired glucose tolerance was highly (>99%) specific for later diagnosis of diabetes. CONCLUSIONS: Primary care consultations and drug utilization are increased from 5 years before diagnosis of diabetes. Diagnoses of hypertension, hyperlipidemia, obesity, or coronary heart disease or stroke have moderate sensitivity for subsequent diabetes but are nonspecific. A diagnosis of hyperglycemia has a high specificity for later detection of diabetes.

Variations in antibiotic prescribing and consultation rates for acute respiratory infection in UK general practices 1995-2000.

BACKGROUND: Antibiotic prescribing by GPs in the UK has declined since 1995. AIM: We investigated whether general practices that issue fewer antibiotic prescriptions to patients presenting with acute respiratory infections had lower consultation rates for these conditions. DESIGN OF STUDY: Retrospective data analysis. SETTING: UK general practice. METHOD: We analysed data from the General Practice Research Database, including all registered patients from 108 practices between 1995 and 2000. For each practice, numbers of consultations for acute respiratory tract infections and the proportion of consultations resulting in an antibiotic prescription were obtained. An age- and sex-standardised consultation ratio (SCR) and standardised prescription ratio (SPR) were calculated for each practice. We evaluated whether SPR and SCR values were associated. RESULTS: For the mid-year data (1997), the crude consultation rate for all acute respiratory infections ranged from 125-1,110 per 1,000 registered patients at different practices; the proportion of consultations with antibiotics prescribed ranged from 45-98%. After standardising for varying age and sex structure of practice populations, practices with lower SPR values had lower SCR values (r = 0.41; P<0.001). This association was observed in each study year. Moreover, practices that demonstrated reductions in SPR between 1995 and 2000 also showed reductions in SCR (r = 0.27; P = 0.005). CONCLUSION: Practices that prescribe antibiotics to a smaller proportion of patients presenting with acute respiratory infections have lower consultation rates for these conditions. Practices that succeed, over time, in reducing antibiotic prescribing also experience reductions in consultation rates for these conditions. Although our methodology cannot prove that these two findings are causally related, they imply that patients alter their illness behaviour and that this may be a response to previous consultation experience. In consequence, respiratory illness in the community may be undergoing a process of de-medicalisation.

Newborn bloodspot results: predictive value of screen positive test for thalassaemia major.

AIM: There are limited published data on the performance of the percentage of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. This paper aims to analyse data derived from a national newborn bloodspot screening programme for sickle cell disease on the performance of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. METHODS: Newborn bloodspot sickle cell screening data from 2,288,008 babies were analysed. Data reported to the NHS Sickle Cell and Thalassaemia Screening Programme in England for the period 2005 to 2012 were also reviewed to identify any missed cases (4,599,849 babies). RESULTS: Within the cohort of 2,288,008 births, 170 babies were identified as screen positive for beta thalassaemia major using a cut-point of 1.5% HbA. There were 51 identified through look-back methods and 119 prospectively identified from 4 screening laboratories. Among 119 babies with prospective data, 7 were lost to follow up and 15 were false positive results. Using a cut-off value of 1.5% Hb A as a percentage of the total haemoglobin as a screening test for beta thalassaemia major in the newborn provides an estimated sensitivity of 99% (from the look back arm of the study) with a positive predictive value of 87% (from the prospective arm of the study). Excluding infants born before 32 weeks gestation, the positive predictive value rose to 95%. CONCLUSION: A haemoglobin A value of less than 1.5% is a reliable screening test for beta thalassaemia major in the newborn period.

Positive screening and carrier results for the England-wide universal newborn sickle cell screening programme by ethnicity and area for 2005-07.

AIMS: The overall aim of the new national newborn programme is to identify infants at risk of sickle cell disease to allow early detection and to minimise deaths and complications. METHODS: Universal screening for sickle cell disease was introduced in England between September 2003 and July 2006. The 13 newborn laboratories each screen between 25,000 and 110,000 babies a year using the existing dried bloodspot cards. The specified conditions to be screened for include sickle cell anaemia (Hb SS), Hb SC disease, Hb S/beta thalassaemia, Hb S/D(Punjab) and Hb S/O(Arab). Data are reported on screening results by ethnic group and geographical area. RESULTS: The prevalence of screen positive results across England is 1:2000. There is a 25-fold variation by geographical area. African babies make up 61% of all screen positive results despite representing only 4% of total births. Combined carrier rates vary widely by ethnicity, from 1.85 per 1000 (1:540) in 'White British' to 145 per 1000 (1:7) in 'African' babies. Refusal rates for screening show variation by ethnicity. CONCLUSIONS: These results provide useful information both about the frequency of these conditions and the carrier state and their geographic and ethnic distribution across England. This can be used to refine counselling information and are also useful to target and plan services and public information.

Alarm symptoms and identification of non-cancer diagnoses in primary care: cohort study.

OBJECTIVE: To evaluate the predictive value of alarm symptoms for specified non-cancer diagnoses and cancer diagnoses in primary care. DESIGN: Cohort study using the general practice research database. SETTING: 128 general practices in the UK contributing data, 1994-2000. PARTICIPANTS: 762 325 patients aged 15 or older. MAIN OUTCOME MEASURES: Up to 15 pre-specified, non-cancer diagnoses associated with four alarm symptoms (haematuria, haemoptysis, dysphagia, rectal bleeding) at 90 days and three years after the first recorded alarm symptom. For each outcome analyses were implemented separately in a time to event framework. Data were censored if patients died, left the practice, or reached the end of the study period. RESULTS: We analysed data on first episodes of haematuria (11 108), haemoptysis (4812), dysphagia (5999), or rectal bleeding (15 289). Non-cancer diagnoses were common in patients who presented with alarm symptoms. The proportion diagnosed with either cancer or non-cancer diagnoses generally increased with age. In patients presenting with haematuria, the proportions diagnosed with either cancer or non-cancer diagnoses within 90 days were 17.5% (95% confidence interval 16.4% to 18.6%) in women and 18.3% (17.4% to 19.3%) in men. For the other symptoms the proportions were 25.7% (23.8% to 27.8%) and 24% (22.5% to 25.6%) for haemoptysis, 17.2% (16% to 18.5%) and 22.6% (21% to 24.3%) for dysphagia, and 14.5% (13.7% to 15.3%) and 16.7% (15.8% to 17.5%) for rectal bleeding. CONCLUSION: Clinically relevant diagnoses are made in a high proportion of patients presenting with alarm symptoms. For every four to seven patients evaluated for haematuria, haemoptysis, dysphagia, or rectal bleeding, relevant diagnoses will be identified in one patient within 90 days.

Diabetes diagnosis, resource utilization, and health outcomes.

OBJECTIVE: To determine the effect of a clinical diagnosis of diabetes mellitus (DM) on healthcare utilization and health outcomes. STUDY DESIGN: Cohort study. METHODS: A total of 197 United Kingdom family practices with 4974 subjects (mean age, 62.8 years; 52.2% men) with type 2 DM and 9948 matched nondiabetic control subjects. Healthcare utilization and the occurrence of complications were estimated from 2 years before to 2 years after the first clinical diagnosis of DM. RESULTS: From 24 months before the DM diagnosis, primary care consultations were increased in prediagnosis cases compared with controls (relative rate [RR], 1.31; 95% confidence interval [CI], 1.27-1.35), as were emergency and hospital care consultations, hospital specialist referrals, and prescription drug items. At diagnosis of DM, utilization of all forms of healthcare was increased (RR, 4.27; 95% CI, 4.17-4.36 for primary care consultations; RR, 2.49; 95% CI, 2.46-2.52 for prescription drug items). In the quarter following diagnosis, healthcare utilization was increased for acute myocardial infarction (RR, 6.29; 95% CI, 2.69-14.73), cerebrovascular disease (RR, 5.14; 95% CI, 3.37-7.84), ischemic heart disease (RR, 3.65; 95% CI, 2.77-4.80), and peripheral nerve disorders (RR, 5.01; 95% CI, 2.81-8.95). First diagnoses of myocardial infarction, cerebrovascular disease, and peripheral nerve disorders were increased during the period from 6 months before to 6 months after diagnosis. CONCLUSIONS: Clinical diagnosis of DM is often the end of a process leading to established complications and is associated with greatly increased utilization of care. This adds to the justification of strategies for earlier detection of hyperglycemic states.

Explaining the decline in early mortality in men and women with type 2 diabetes: a population-based cohort study.

OBJECTIVE: The purpose of this study was to test the hypothesis that changing utilization of lipid-lowering, antihypertensive, and oral hypoglycemic drugs may be associated with trends in all-cause mortality in men and women with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a cohort study in 197 general practices in the U.K. General Practice Research Database including 48,579 subjects with type 2 diabetes first diagnosed between 1996 and 2006. Measures included all-cause mortality and prescription of hypoglycemic, lipid-lowering, and antihypertensive drugs. RESULTS: From 1996 to 2006, incidence of type 2 diabetes increased and the mean age at diagnosis declined in women. Prescription of statins within 12 months of diagnosis increased (1996, women 4.9%, men 5.1%; 2005, women 63.5%, men 71.0%), as did drugs acting on the renin-angiotensin system (1996, women 19.4%, men 21.5%; 2005, women 45.5%, men 54.6%) and metformin (1996, women 19.1%, men 15.8%; 2005, women 45.5%, men 42.8%), whereas prescription of sulfonylureas declined. All-cause mortality in the first 24 months after diabetes diagnosis declined in men from 47.9 per 1,000 person-years for subjects with diabetes diagnosed in 1996 to 25.2 for subjects with diabetes diagnosed in 2006 and in women from 37.4 in 1996 to 27.6 in 2006. In a multiple regression model adjusting for age and comorbidity, prescription of statins before or after diagnosis, renin-angiotensin system drugs before or after diagnosis, and metformin after diagnosis were associated with lower mortality. CONCLUSIONS: Widespread implementation of more effective prescribing to control lipids, blood glucose, and blood pressure may have contributed to recent declines in early mortality in men and women with type 2 diabetes.

Sudden infant death syndrome and maternal depression.

OBJECTIVE: To investigate whether there is an association between sudden infant death syndrome (SIDS) and perinatal depression. METHOD: A case-control study design was used. Cases included women registered in a British primary care database with a live birth (1987-2000) and a subsequent SIDS death. Controls were women with a live birth born in the same year as the matched SIDS death, with infant survival for the first year of life. RESULTS: One hundred sixty-nine linked mother-infant cases of SIDS were matched with 662 mother-infant controls. The authors found that SIDS was independently associated with maternal depression in the year before birth (odds ratio [OR] = 4.93, 95% CI = 1.10 to 22.05), smoking (OR = 2.50, 95% CI = 1.29 to 4.88), and male sex (OR = 1.94, 95% CI = 1.04 to 3.64). There was weak evidence of an independent association of SIDS with depression in the 6 months after birth, before the index SIDS death (OR = 1.80, 95% CI = 0.71 to 4.56). CONCLUSION: This study provides further evidence for an association between SIDS and perinatal depression, particularly antenatal depression. Health care professionals should ensure that women with perinatal depression are appropriately treated and are provided with clear advice on infant care practices that may prevent SIDS.

Alarm symptoms in early diagnosis of cancer in primary care: cohort study using General Practice Research Database.

OBJECTIVE: To evaluate the association between alarm symptoms and the subsequent diagnosis of cancer in a large population based study in primary care. DESIGN: Cohort study. SETTING: UK General Practice Research Database. Patients 762 325 patients aged 15 years and older, registered with 128 general practices between 1994 and 2000. First occurrences of haematuria, haemoptysis, dysphagia, and rectal bleeding were identified in patients with no previous cancer diagnosis. MAIN OUTCOME MEASURE: Positive predictive value of first occurrence of haematuria, haemoptysis, dysphagia, or rectal bleeding for diagnoses of neoplasms of the urinary tract, respiratory tract, oesophagus, or colon and rectum during three years after symptom onset. Likelihood ratio and sensitivity were also estimated. RESULTS: 11.108 first occurrences of haematuria were associated with 472 new diagnoses of urinary tract cancers in men and 162 in women, giving overall three year positive predictive values of 7.4% (95% confidence interval 6.8% to 8.1%) in men and 3.4% (2.9% to 4.0%) in women. After 4812 new episodes of haemoptysis, 220 diagnoses of respiratory tract cancer were made in men (positive predictive value 7.5%, 6.6% to 8.5%) and 81 in women (4.3%, 3.4% to 5.3%). After 5999 new diagnoses of dysphagia, 150 diagnoses of oesophageal cancer were made in men (positive predictive value 5.7%, 4.9% to 6.7%) and 81 in women (2.4%, 1.9 to 3.0%). After 15 289 episodes of rectal bleeding, 184 diagnoses of colorectal cancer were made in men (positive predictive value 2.4%, 2.1% to 2.8%) and 154 in women (2.0%, 1.7% to 2.3%). Predictive values increased with age and were strikingly high, for example, in men with haemoptysis aged 75-84 (17.1%, 13.5% to 21.1%) and in men with dysphagia aged 65-74 (9.0%, 6.8% to 11.7%). CONCLUSION: New onset of alarm symptoms is associated with an increased likelihood of a diagnosis of cancer, especially in men and in people aged over 65. These data provide support for the early evaluation of alarm symptoms in an attempt to identify underlying cancers at an earlier and more amenable stage.

Predictive validity of different definitions of hypertension for type 2 diabetes.

BACKGROUND: Models to predict diabetes or pre-diabetes often incorporate the assessment of hypertension, but proposed definitions for 'hypertension' are inconsistent. We compared the classifications obtained using different definitions for 'hypertension'. METHODS: We compared records for 5158 cases from 181 family practices, who were later diagnosed with diabetes and prescribed oral hypoglycaemic drugs, with 5158 controls, matched for age, sex and family practice, who were never diagnosed with diabetes. We compared classifications obtained using definitions of hypertension based on medical diagnoses, prescription of blood pressure lowering drugs or both. We compared family practices where diagnosis or prescribing varied systematically. RESULTS: Classification of hypertension based on recorded medical diagnoses gave a sensitivity of 32.2% for diabetes (95% confidence interval from 30.4 to 34.1%). Prescription of blood pressure lowering drugs in the 12 months before diagnosis gave a sensitivity of 47.2% (45.7 to 48.7%). Combining either a medical diagnosis or a blood pressure lowering prescription gave a sensitivity of 52.8% (51.3 to 54.3%). In family practices where hypertension was least frequently recorded, a diagnosis of hypertension gave a sensitivity of 19.5% for diabetes (17.4 to 21.6%) compared with 50.8% (46.3 to 55.3%) in the highest quintile. Prescription of blood pressure lowering drugs gave a sensitivity of 36.1% (33.1 to 39.0%) in the lowest prescribing practices but 58.2% (55.5 to 61.0%) in the highest quintile. CONCLUSIONS: Misclassification errors depend on the definition of hypertension and its implementation in practice. Definitions of hypertension that depend on access or quality in health care should be avoided.

Mortality in type 2 diabetic subjects prescribed metformin and sulphonylurea drugs in combination: cohort study.

BACKGROUND: In the UK Prospective Diabetes Study, treatment with sulphonylurea and metformin in combination was associated with increased mortality. We compared mortality in subjects treated either with metformin or sulphonylurea drugs alone, or in combination. METHODS: Cohort study in 263 general practices in the United Kingdom. Subjects were aged >/=30 years. Outcome was survival from first prescription of oral hypoglycaemic drugs till death from any cause. Transfer to metformin and sulphonylurea in combination was modelled as a time-dependent covariate. Hazard ratios were adjusted for age, sex, year of treatment, presence of coronary heart disease or prescription of cardiovascular drugs. Analyses were also stratified by propensity score. RESULTS: There were 8488 subjects who were initially prescribed sulphonylureas with a total of 20 783 person years of follow-up and 1157 deaths. The crude mortality rate was 58.56 per 1000 person years during suphonlyurea as sole treatment. In 1868 subjects who were prescribed additional metformin, the mortality rate was 39.75 per 1000. The adjusted hazard ratio was 1.06 (95% confidence interval 0.85 to 1.31, P = 0.616). There were 3099 subjects initially treated with metformin with a total of 7306 person years of follow-up and 176 deaths. During metformin-only treatment, the mortality rate was 25.48 per 1000. After addition of sulphonylurea in 867 subjects, mortality was 19.35 per 1000. The adjusted hazard ratio was 0.95 (0.64 to 1.40, P = 0.801). CONCLUSIONS: In this large non-randomized study, there was no evidence of increased mortality risk following prescription of sulphonylurea and metformin in combination, as compared to either drug prescribed singly.

Why has antibiotic prescribing for respiratory illness declined in primary care? A longitudinal study using the General Practice Research Database.

BACKGROUND: Antibiotic prescribing by general practitioners (GPs) increased in the 1980s and peaked in 1995. Prescribing volumes subsequently fell by over a quarter between 1995 and 2000, mostly accounted for by reduced antibiotic prescribing for acute respiratory illnesses. We aimed to investigate changes in consultation rates and the proportion of consultations with antibiotics prescribed for different types of respiratory tract infections. METHODS: Data were derived from 108 UK general practices, covering a mean of 642,685 patients, reporting data to the General Practice Research Database (GPRD) continuously between 1994 and 2000. OUTCOME MEASURES: annual age- and sex-standardized consultation rates for 11 different acute respiratory infections per 1000 registered patients and proportions of these consultations resulting in an antibiotic prescription. RESULTS: The standardized consultation rate for 'any respiratory infection' declined by 35 per cent from 422 to 273 per 1000 registered patients, per year. The largest relative reductions in consultation rates were observed for 'common cold' (50 per cent), 'laryngitis' (43 per cent) and 'sore throat' (43 per cent). The standardized proportion of consultations that resulted in an antibiotic prescription for 'any respiratory infection' declined from 79 per cent in 1994 to 67 per cent in 2000. The largest relative reductions in antibiotic prescribing rates occurred in patients recorded as suffering from 'influenza' (52 per cent), 'upper respiratory tract infections' (33 per cent) and 'laryngitis' (30 per cent). Overall, antibiotic prescriptions for all acute respiratory infections declined by 45 per cent. CONCLUSION: The reduction in antibiotic prescribing in common respiratory infections between 1994 and 2000 has occurred partly because GPs are prescribing antibiotics less frequently when patients consult but mainly because there are fewer consultations with these conditions. Further work should aim to understand the reasons for the decline in consultations for respiratory infections and whether further reductions in antibiotic prescribing are feasible.