Market penetration of new drugs in one United Kingdom region: implications for general practitioners and administrators.

OBJECTIVE--To determine the use of new drugs in one United Kingdom region. DESIGN--Examination of data on prescribing of angiotensin converting enzyme inhibitors, new broad spectrum antibiotics, and H2 receptor antagonists. Calculation of number of defined daily doses prescribed each month. SETTING--All general practices in Northern Ireland. MAIN OUTCOME MEASURES--Drug use index and market share of each drug. RESULTS--During 1988-91 prescribing of angiotensin converting enzyme inhibitors increased by 126%, of H2 receptor antagonists by 46%, and of new antibiotics by 207%. The first drug on the market usually retained the largest market share. Use of oral antibiotics increased threefold irrespective of the reporting policy of the general practitioners'' local laboratory. CONCLUSIONS--The increase in prescribing of these drugs seems to be greater than can be accounted for by an increase in patients with specific indications for these drugs. This suggests that the profession has not instituted effective checks to ensure that the legitimate promotion of new products does not lead to inappropriate and wasteful use.     

Prevalence and antimicrobial susceptibilities of bacteria isolated from blood cultures of hospitalized patients in the United States in 2002

Background

Upper respiratory tract infections (URTIs) are among the most frequent reasons for physician office visits in paediatrics. Despite their predominant viral aetiology, URTIs continue to be treated with antimicrobials. We explored general practitioners' (GPs) prescribing behaviour for antimicrobials in children (≤ 16 years) with URTIs in Trinidad, using the guidelines from the Centers for Disease Control and Prevention (CDC) as a reference.

Methods

A cross-sectional study was conducted on 92 consenting GPs from the 109 contacted in Central and East Trinidad, between January to June 2003. Using a pilot-tested questionnaire, GPs identified the 5 most frequent URTIs they see in office and reported on their antimicrobial prescribing practices for these URTIs to trained research students.

Results

The 5 most frequent URTIs presenting in children in general practice, are the common cold, pharyngitis, tonsillitis, sinusitis and acute otitis media (AOM) in rank order. GPs prescribe at least 25 different antibiotics for these URTIs with significant associations for amoxicillin, co-amoxiclav, cefaclor, cefuroxime, erythromycin, clarithromycin and azithromycin (p < 0.001). Amoxicillin alone or with clavulanate was the most frequently prescribed antibiotic for all URTIs. Prescribing variations from the CDC recommendations were observed for all URTIs except for AOM (50%), the most common condition for antibiotics. Doctors practicing for >30 years were more likely to prescribe antibiotics for the common cold (p = 0.014). Severity (95.7%) and duration of illness (82.5%) influenced doctors' prescribing and over prescribing in general practice was attributed to parent demands (75%) and concern for secondary bacterial infections (70%). Physicians do not request laboratory investigations primarily because they are unnecessary (86%) and the waiting time for results is too long (51%).

Conclusions

Antibiotics are over prescribed for paediatric URTIs in Trinidad and amoxicillin with co-amoxiclav were preferentially prescribed. Except for AOM, GPs' prescribing varied from the CDC guidelines for drug and duration. Physicians recognise antibiotics are overused and consider parents expecting antibiotics and a concern for secondary bacterial infections are prescribing pressures. Guidelines to manage URTIs, ongoing surveillance programs for antibiotic resistance, public health education on non-antibiotic strategies, and postgraduate education for rational pharmacotherapy in general practice would decrease inappropriate antibiotic use in URTIs.     

Salmonella enterica serotype Bredeney: antimicrobial susceptibility and molecular diversity of isolates from Ireland and Northern Ireland.

Salmonella enterica serotype Bredeney has emerged as the third most commonly identified serotype among human clinical isolates referred to the Irish National Salmonella Reference Laboratory in the years 1998 to 2000. A collection of 112 isolates of S. enterica serotype Bredeney collected during the period 1995 to 1999 from animal, food, and human sources from both Ireland and Northern Ireland were studied. Antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), and DNA amplification fingerprinting (DAF) were performed on all isolates. Plasmid profiles were examined on a subset of 33 isolates. A high proportion (74%) of isolates were susceptible to all antimicrobial agents tested. Resistance to both sulfonamide and trimethoprim was observed in 21% of isolates, and resistance to multiple (five) antimicrobial agents was observed in a single isolate (0.9%). Eight different PFGE patterns were obtained, with 87% of isolates grouping as PFGE type A. PFGE type A was predominant in animals, food, and humans. There was good overall concordance between the groups identified by PFGE and DAF. Overall results indicate that most S. enterica serotype Bredeney isolates in Ireland and Northern Ireland from animal and human sources are clonally related.     

Family size and religious denomination in Northern Ireland

During the summer of 1983, a provincewide representative sample of all ever-married women and single women with children, under the age of 60, was interviewed to examine variations in family size in Northern Ireland. The valuation list of domestic dwellings was used as the sample frame and a clustered sample was drawn from this using the 526 electoral wards as individual clusters. Wards were stratified according to socioeconomic structure, religion, location within Northern Ireland, and whether they were predominatly rural or urban. Sampling within selected clusters was on a systematic basis and proportional to population size. For women currently married, 1 in 5 of the husbands was interviewed using a shorter questionnaire focusing on attitudes to fertility. Of the 3914 houseolds where contact was made and which contained an eligible female, there were 2997 successful interviews with females, giving an effective response rate of 77%. An additional 392 interviews were obtained from husbands. The most persistent fertility differential in Northern Ireland going back at least to the beginning of the 20th century has been that between Protestants and Roman Catholics. According to these preliminary findings, this remains the case. The average number of children born alive to ever-married Roman Catholic females was 3.24 in 1983, compared with 2.29 children for the corresponding group of non-Catholic women. Yet, the survey relates to an instant during a peirod of considerable flux in Roman Catholic fertliity, and comparison of these 1983 data with those collected at the 1971 census of population shows that Roman Catholic family size declined by 11% over the intervening 12 years, although this is marginally reduced after standardization for changes in the age structure of ever-married women. Non-Catholic family size, by contrast, remained virtually static during the same time period. The pace of change has been more pronounced in Belfast and its suburbs. Data are not yet available from the survey to chart these processes by marriage cohort, but some pointers can be obtained from the tabulation of family size by denomination and age of mother. With the exception of the under-20 age group, the average size of Roman Catholic families was consistently and substantially larger than that of the corresponding non-Catholic age group. The absolute difference in terms of mean numbers of children widened steadily with increasing age. These preliminary data also show that there is still a strong geographical dimension to the religious differential in fertility. Average family size was larger in rural than urban areas but moreso for Roman Catholics (16% larger) than for non-Catholics (9% larger). Although differences in family size between Roman Catholics and non-Catholics still prevail, there has been a considerable degree of overall convergence since 1971.     

Public Beliefs on Antibiotics and Symptoms of Respiratory Tract Infections among Rural and Urban Population in Poland: A Questionnaire Study

Introduction

General public views and expectations around the use of antibiotics can influence general practitioners'' antibiotic prescribing decisions. We set out to describe the knowledge, attitudes and beliefs about the use of antibiotics for respiratory tract infections in adults in Poland, and explore differences according to where people live in an urban-rural continuum.

Material and Methods

Face to face survey among a stratified random sample of adults from the general population.

Results

1,210 adults completed the questionnaire (87% response rate); 44.3% were rural; 57.9% were women. 49.4% of rural respondents and 44.4% of urban respondents had used an antibiotic in the last 2 years. Rural participants were less likely to agree with the statement “usually I know when I need an antibiotic,” (53.5% vs. 61.3% respectively; p = 0.015) and reported that they would consult with a physician for a cough with yellow/green phlegm (69.2% vs. 74.9% respectively; p = 0.004), and were more likely to state that they would leave the decision about antibiotic prescribing to their doctor (87.5% vs. 85.6% respectively; p = 0.026). However, rural participants were more likely to believe that antibiotics accelerate recovery from sore throat (45.7% vs. 37.1% respectively; p = 0.017). Use of antibiotic in the last 2 years, level of education, number of children and awareness of the problem of developing antimicrobial resistance predicted accurate knowledge about antibiotic effectiveness.

Conclusions

There were no major differences in beliefs about antibiotics between urban and rural responders, although rural responders were slightly less confident in their knowledge about antibiotics and self-reported greater use of antibiotics. Despite differences in the level of education between rural and urban responders, there were no significant differences in their knowledge about antibiotic effectiveness.     

Medical audit in general practice. I: Effects on doctors' clinical behaviour for common childhood conditions. North of England Study of Standards and Performance in General Practice.

OBJECTIVE--To estimate the effects of medical audit, particularly setting clinical standards, on general practitioners'' clinical behaviour. DESIGN--Before and after study strengthened by a replicated Latin square. SETTING--62 training general practices in the north of England. SUBJECTS--92 general practitioner trainers, 84 (91%) of whom completed the study; random sample of 3500 children consulting one of these trainers for any of five conditions--acute cough, acute vomiting, bedwetting, itchy rash, and recurrent wheezy chest--stratified by doctor consulted, condition, and age. INTERVENTIONS--Clinical standard set by each of 10 small groups of general practitioner trainers for one randomly selected childhood condition. Each group also experienced a different type of medical audit, randomly selected, for each of the four other study conditions (receiving a clinical standard set by another trainer group, tabulated data comparing clinical performance with that of all other groups, tabulated data from only their own group, and nothing ("control" condition)). MAIN MEASURES--Content of initial consultation divided into: history, examination, investigation, diagnosis, and management (abstracted from medical records and "enhancement forms" completed by doctors). RESULTS--There was increased prescribing of bronchodilators for acute cough, oral rehydration fluids for acute vomiting, antibiotics for itchy rash, and bronchodilators and oral steroids for recurrent wheezy chest and reduced prescribing of antibiotics for acute cough and recurrent wheezy chest and tricyclic antidepressants for bedwetting. Fewer children were "discharged." Each change was consistent with the standard and either limited to doctors who set a standard for that condition or significantly greater for them than all other doctors. CONCLUSION--Setting clinical standards improved prescribing and follow up.     

Association between Antibiotic Prescribing in Pregnancy and Cerebral Palsy or Epilepsy in Children Born at Term: A Cohort Study Using The Health Improvement Network

Background

Between 19%-44% pregnant women are prescribed antibiotics during pregnancy. A single, large randomised-controlled-trial (ORACLE Childhood Study II) found an increased risk of childhood cerebral palsy and possibly epilepsy following prophylactic antibiotic use in pregnant women with spontaneous preterm labour. We ascertained whether this outcome could be reproduced across the population of babies delivered at term and prospectively followed in primary-care using data from The Health Improvement Network.

Methods

We determined the risk of cerebral palsy or epilepsy in children whose mothers were prescribed antibiotics during pregnancy using a cohort of 195,909 women linked to their live, term-born, singleton children. We compared the effect of antibiotic class, number of courses and timing of prescribing in pregnancy. Analyses were adjusted for maternal risk factors (e.g. recorded infection, age, chronic conditions, social deprivation, smoking status). Children were followed until age seven years or cessation of registration with the primary-care practitioner.

Results

In total, 64,623 (33.0%) women were prescribed antibiotics in pregnancy and 1,170 (0.60%) children had records indicating cerebral palsy or epilepsy. Adjusted analyses showed no association between prescribing of any antibiotic and cerebral palsy or epilepsy (adj.HR 1.04, 95%CI 0.91–1.19). However, compared with penicillins, macrolides were associated with an increased risk of cerebral palsy or epilepsy (adj.HR 1.78, 95%CI 1.18–2.69; number needed to harm 153, 95%CI 71–671).

Conclusions

We found no overall association between antibiotic prescribing in pregnancy and cerebral palsy and/or epilepsy in childhood. However, our finding of an increased risk of cerebral palsy or epilepsy associated with macrolide prescribing in pregnancy adds to evidence that macrolide use is associated with serious harm.     

Is racism the new sectarianism? Negativity towards immigrants and ethnic minorities in Northern Ireland from 2004 to 2015

Negativity towards ethnic minorities is a serious problem in Northern Ireland. Its history of the Troubles around religious identities makes Northern Ireland a special case in Europe. This paper examines negativity towards Muslims, Eastern Europeans and immigrants in Northern Ireland using data from the Northern Ireland Life and Times Survey and the British Social Attitudes Survey. The results from regressions show that anti-immigrant negativity is no more prevalent in Northern Ireland than elsewhere in the UK. However, levels of negativity towards Muslims and Eastern Europeans are significantly higher than in Great Britain and have increased in recent years, particularly among young adults aged 18–24 years, although older cohorts are more intolerant on average. Our regression analyses found strong positive relationships between anti-immigrant negativity, sectarianism and perceived neighbourhood segregation. Higher education, contacts with minority members and (religiously) mixed schooling are negatively related to negativity towards immigrants.     

Evaluation of a web-based intervention to reduce antibiotic prescribing for LRTI in six European countries: quantitative process analysis of the GRACE/INTRO randomised controlled trial

Background

To reduce the spread of antibiotic resistance, there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI. This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries. The aim was to understand how the interventions were implemented and to examine effects of the interventions on general practitioners’ (GPs’) and patients’ attitudes.

Methods

GPs were cluster randomised to one of three intervention groups or a control group. The intervention groups received web-based training in either use of the C-reactive protein (CRP) test, communication skills and use of a patient booklet, or training in both. GP attitudes were measured before and after the intervention using constructs from the Theory of Planned Behaviour and a Website Satisfaction Questionnaire. Effects of the interventions on patients were assessed by a post-intervention questionnaire assessing patient enablement, satisfaction with the consultation, and beliefs about the risks and need for antibiotics.

Results

GPs in all countries and intervention groups had very positive perceptions of the intervention and the web-based training, and felt that taking part had helped them to reduce prescribing. All GPs perceived reducing prescribing as more important and less risky following the intervention, and GPs in the communication groups reported increased confidence to reduce prescribing. Patients in the communication groups who received the booklet reported the highest levels of enablement and satisfaction and had greater awareness that antibiotics could be unnecessary and harmful.

Conclusions

Our findings suggest that the interventions should be broadly acceptable to both GPs and patients, as well as feasible to roll out more widely across Europe. There are also some indications that they could help to engender changes in GP and patient attitudes that will be helpful in the longer-term, such as increased awareness of the potential disadvantages of antibiotics and increased confidence to manage LRTI without them. Given the positive effects of the booklet on patient beliefs and attitudes, it seems logical to extend the use of the patient booklet to all patients.

     

Prescribing patterns of antibiotics and sensitivity patterns of common microorganisms in the Internal Medicine ward of a teaching hospital in Western Nepal: a prospective study

Background

Information about antibiotic use and resistance patterns of common microorganisms are lacking in hospitals in Western Nepal. Excessive and inappropriate use of antibiotics contributes to the development of bacterial resistance. The parameter: Defined daily dose/100 bed-days, provides an estimate of consumption of drugs among hospital in-patients. This study was carried out to collect relevant demographic information, antibiotic prescribing patterns and the common organisms isolated including their antibiotic sensitivity patterns.

Methods

The study was carried out over a 3-month period (01.04.2002 to 30.06.2002) at the Manipal Teaching Hospital, Western Nepal. The median number of days of hospitalization and mean ± SD cost of antibiotics prescribed during hospital stay were calculated. The use of antibiotics was classified for prophylaxis, bacteriologically proven infection or non-bacteriologically proven infection. Sensitivity patterns of the common organisms were determined. Defined daily dose/100 bed-days of the ten most commonly prescribed antibiotics were calculated.

Results

203 patients were prescribed antibiotics; 112 were male. Median duration of hospitalization was 5 days. 347 antibiotics were prescribed. The most common were ampicillin, amoxicillin, metronidazole, ciprofloxacin and benzylpenicillin. Mean ± SD cost of antibiotics was 16.5 ± 13.4 US$. Culture and sensitivity testing was carried out in 141 patients. The common organisms isolated were H. influenzae, E. coli, K. pneumoniae and S. aureus.

Conclusions

Antibiotic resistance is becoming a problem in the Internal Medicine ward. Formulation of a policy for hospital antibiotic use and an educational programme especially for junior doctors is required.     

Salmonella enterica Serotype Bredeney: Antimicrobial Susceptibility and Molecular Diversity of Isolates from Ireland and Northern Ireland

Salmonella enterica serotype Bredeney has emerged as the third most commonly identified serotype among human clinical isolates referred to the Irish National Salmonella Reference Laboratory in the years 1998 to 2000. A collection of 112 isolates of S. enterica serotype Bredeney collected during the period 1995 to 1999 from animal, food, and human sources from both Ireland and Northern Ireland were studied. Antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), and DNA amplification fingerprinting (DAF) were performed on all isolates. Plasmid profiles were examined on a subset of 33 isolates. A high proportion (74%) of isolates were susceptible to all antimicrobial agents tested. Resistance to both sulfonamide and trimethoprim was observed in 21% of isolates, and resistance to multiple (five) antimicrobial agents was observed in a single isolate (0.9%). Eight different PFGE patterns were obtained, with 87% of isolates grouping as PFGE type A. PFGE type A was predominant in animals, food, and humans. There was good overall concordance between the groups identified by PFGE and DAF. Overall results indicate that most S. enterica serotype Bredeney isolates in Ireland and Northern Ireland from animal and human sources are clonally related.     

Phenylketonuria and the peoples of Northern Ireland

The comparison of regional patterns of recessive disease mutations is a new source of information for studies of population genetics. The analysis of phenylketonuria (PKU) mutations in Northern Ireland shows that most major episodes of immigration have left a record in the modern genepool. The mutation I65T can be traced to the Palaeolithic people of western Europe who, in the Mesolithic period, first colonised Ireland. R408W (on haplotype 1) in contrast, the most common Irish PKU mutation, may have been prevalent in the Neolithic farmers who settled in Ireland after 4500 BC. No mutation was identified that could represent European Celtic populations, supporting the view that the adoption of Celtic culture and language in Ireland did not involve major migration from the continent. Several less common mutations can be traced to the Norwegian Atlantic coast and were probably introduced into Ireland by Vikings. This indicates that PKU has not been brought to Norway from the British Isles, as was previously argued. The rarity in Northern Ireland of IVS12nt1, the most common mutation in Denmark and England, indicates that the English colonialisation of Ireland did not alter the local genepool in a direction that could be described as Anglo-Saxon. Our results show that the culture and language of a population can be independent of its genetic heritage, and give some insight into the history of the peoples of Northern Ireland. Received: 23 October 1996 / Accepted: 26 February 1997     

Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication

Background:When prescribing antibiotics for common indications, clinicians need information about both harms and benefits, information that is currently available only from observational studies. We quantified the common harms of the most frequently prescribed antibiotic, amoxicillin, from randomized placebo-controlled trials.Methods:For this systematic review, we searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, without language restriction, for any randomized, participant-blinded, placebo-controlled trials of amoxicillin or amoxicillin–clavulanic acid for any indication, in any setting. Our main outcome was any reported adverse event.Results:Of 730 studies identified, we included 45 trials: 27 involving amoxicillin, 17 involving amoxicillin–clavulanic acid and 1 involving both. The indications for antibiotic therapy were variable. The risk of bias was low, although only 25 trials provided data suitable for assessment of harms, which suggested under-reporting. Diarrhea was attributed to amoxicillin only in the form of amoxicillin–clavulanic acid (Peto odds ratio [OR] 3.30, 95% confidence interval [CI] 2.23–4.87). The OR for candidiasis (3 trials) was significantly higher (OR 7.77, 95% CI 2.23–27.11). Rashes, nausea, itching, vomiting and abnormal results on liver function tests were not significantly increased. The results were not altered by sensitivity analyses, nor did funnel plots suggest publication bias. The number of courses of antibiotics needed to harm was 10 (95% CI 6–17) for diarrhea with amoxicillin–clavulanic acid and 27 (95% CI 24–42) for candidiasis with amoxicillin (with or without clavulanic acid).Interpretation:Diarrhea was caused by use of amoxicillin–clavulanic acid, and candidiasis was caused by both amoxicillin and amoxicillin–clavulanic acid. Harms were poorly reported in most trials, and their true incidence may have been higher than reported. Nevertheless, these rates of common harms associated with amoxicillin therapy may inform decisions by helping clinicians to balance harms against benefits.Most antibiotics are prescribed by primary care clinicians for common infections, particularly acute respiratory infections.¹ However, for most acute respiratory infections, antibiotics provide only marginal benefits, and an inevitable consequence of this injudicious use is the prospect of antibiotic resistance. One way to reduce antibiotic prescribing in primary care is to explain to patients how little these drugs help for many common infections and to apply a process of shared decision-making during the consultation.²The practice of shared decision-making requires not just an explanation of the paucity of benefits of antibiotics in most primary care situations, but also an explanation of the potential harms. Serious harms are probably sufficiently rare to be discounted by most clinicians and their patients.³ Yet when the decision to use or not use antibiotics relates to a self-remitting illness, for which the benefits are likely to be modest at best, the more common, mild harms of antibiotics become important. Unfortunately, common harms from antibiotics are poorly quantified, and clinicians cannot talk to patients with confidence about their likelihood.Current understanding of the common harms of antibiotics is derived largely from observational studies. However, estimates of common harms from such studies may be biased, principally because it is difficult to distinguish adverse drug reactions from disease-related symptoms. One approach to addressing this problem is to investigate common harms encountered in randomized controlled trials of antibiotic against placebo. This study design controls for disease-related symptoms, allowing for better quantification of antibiotic-related adverse effects.The most common antibiotic used in primary care is amoxicillin, either alone or in combination with clavulanic acid. “Common harms” can be defined as those frequent enough to be observable in the patient samples of most randomized trials and occurring during the recording of primary outcomes in such studies (with recognition that some of the adverse effects will occur later).Accordingly, we systematically reviewed all published placebo-controlled randomized trials of amoxicillin or amoxicillin–clavulanic acid for any indication, with the rationale that the risks of drug-induced harms are independent of the condition being treated.⁴