New imaging tools to measure nephron number in vivo: opportunities for developmental nephrology.

The mammalian kidney is a complex organ, requiring the concerted function of up to millions of nephrons. The number of nephrons is constant after nephrogenesis during development, and nephron loss over a life span can lead to susceptibility to acute or chronic kidney disease. New technologies are under development to count individual nephrons in the kidney in vivo. This review outlines these technologies and highlights their relevance to studies of human renal development and disease.

Urinary tract infections in very low birthweight infants: A two-center analysis of microbiology, imaging and heart rate characteristics.

BACKGROUND: Increased understanding of characteristics of urinary tract infection (UTI) among very low birthweight infants (VLBW) might lead to improvement in detection and treatment. Continuous monitoring for abnormal heart rate characteristics (HRC) could provide early warning of UTIs. OBJECTIVE: Describe the characteristics of UTI, including HRC, in VLBW infants. METHODS: We reviewed records of VLBW infants admitted from 2005-2010 at two academic centers participating in a randomized clinical trial of HRC monitoring. Results of all urine cultures, renal ultrasounds (RUS), and voiding cystourethrograms (VCUG) were assessed. Change in the HRC index was analyzed before and after UTI. RESULTS: Of 823 VLBW infants (27.7±2.9 weeks GA, 53% male), 378 had > / = 1 urine culture obtained. A UTI (≥10,000 CFU and >five days of antibiotics) was diagnosed in 80 infants, (10% prevalence, mean GA 25.8±2.0 weeks, 76% male). Prophylactic antibiotics were administered to 29 (36%) infants after UTI, of whom four (14%) had another UTI. Recurrent UTI also occurred in 7/51 (14%) of infants not on uroprophylaxis after their first UTI. RUS was performed after UTI in 78%, and hydronephrosis and other major anomalies were found in 19%. A VCUG was performed in 48% of infants and 18% demonstrated vesicoureteral reflux (VUR). The mean HRC rose and fell significantly in the two days before and after diagnosis of UTI. CONCLUSIONS: UTI was diagnosed in 10% of VLBW infants, and the HRC index increased prior to diagnosis, suggesting that continuous HRC monitoring in the NICU might allow earlier diagnosis and treatment of UTI.

Neonatal Acute Kidney Injury: A Survey of Neonatologists' and Nephrologists' Perceptions and Practice Management.

BACKGROUND: Neonatal acute kidney injury (AKI) occurs in 40 to 70% of critically ill neonatal intensive care admissions. This study explored the differences in perceptions and practice variations among neonatologists and pediatric nephrologists in diagnostic criteria, management, and follow-up of neonatal AKI. METHODS: A survey weblink was emailed to nephrologists and neonatologists in Australia, Canada, New Zealand, India, and the United States. Questions consisted of demographic and unit practices, three clinical scenarios assessing awareness of definitions of neonatal AKI, knowledge, management, and follow-up practices. RESULTS: Many knowledge gaps among neonatologists, and to a lesser extent, pediatric nephrologists were identified. Neonatologists were less likely to use categorical definitions of neonatal AKI (p < 0.00001) or diagnose stage 1 AKI (p < 0.00001) than pediatric nephrologists. Guidelines for creatinine monitoring for nephrotoxic medications were reported by 34% (aminoglycosides) and 62% (indomethacin) of respondents. Nephrologists were more likely to consider follow-up after AKI than neonatologists (p < 0.00001). Also, 92 and 86% of neonatologists and nephrologists, respectively, reported no standardization or infrastructure for long-term renal follow-up. CONCLUSION: Neonatal AKI is underappreciated, particularly among neonatologists. A lack of evidence on neonatal AKI contributes to this variation in response. Therefore, dissemination of current knowledge and areas for research should be the priority.

Impact of infections on primary care--greater than expected.

Though infection has declined as a cause of death it consumes a major proportion of primary care resources, and because of antibiotic resistance is increasingly important. We examined the burden of illness attributable to infection in primary care by analysing data from the fourth practice-based national morbidity survey which monitored all consultations by diagnosis in 470,000 persons over a 12 month period from September 1991 to August 1992. Rates of persons consulting, new episodes of illness and consultations were calculated according to the list of infections published by Wilson and Bhopal (W&B list), and as amended by the Communicable Disease Surveillance Centre (CDSC list); selected comparisons were made with national data on hospital derived finished consultant episodes and deaths. Forty-one percent of all registered persons consulted on at least one occasion during the year for infection (estimated by either list). Infections accounted for 40% of all new episodes of illness and 29% of all consultations; respiratory infections accounted for approximately half the infection total. New episode rates were highest in children aged less than 1 year and lowest in males 25-54 years and females 55-64 years. Except in infancy, rates were higher in females. There were 734 episodes of infection annually per 1,000 population reported in general practice compared with 20 per 1,000 finished consultant episodes. The average episode of infection prompted 1.2 general practice consultations. Improved management through more precise diagnosis by near patient tests is desirable, but is unlikely to be obtained cost effectively if consultation numbers or the time spent is substantially increased. These results emphasise the importance of adequate training for general practitioners in the natural history, epidemiology, diagnosis and treatment (pharmacology) of infection.

The prevalence of asthma and heart disease in transport workers: a practice-based study.

BACKGROUND: There has been widespread concern that the increasing incidence of asthma observed during the late 1980s might have arisen because of environmental pollution, and in particular vehicle pollution. The General Practice Morbidity Survey in 1991/92 (MSGP4) collected data on occupation, employment status, and smoking habit linked individually to each patient record. OBJECTIVES: To examine whether people with occupations that have high exposure to vehicle exhaust fumes have an increased prevalence of asthma, acute respiratory infections, and ischaemic heart disease (IHD). METHOD: Men aged 16 to 64 years were grouped by Standard Occupational Classification codes; 93,692 employed and 20,858 not-employed men were studied separately. Those with likely high occupational exposure were grouped together ('all-exposed')--the remainder occupations in corresponding chapters of the code were used as controls. We compared 12-month age and smoking standardised disease prevalence ratios for asthma, chronic obstructive pulmonary disease (COPD), acute respiratory infections (IHD), and all circulatory disorders in the all exposed and individual exposed occupations with their matching controls. Also the mean frequency of consultations per person consulting was calculated for each occupational group and disease. RESULTS: For employed persons, the prevalence ratio (PR) for asthma in the all-exposed, (116, 95% confidence interval [95% CI] = 101-130) exceeded that for all employed persons (100); however, the difference compared with chapter-matched controls (PR = 97, 95% CI = 92-103), was not statistically significant. Results for COPD were similar. Prevalence ratios in motor mechanics, a high-exposure group, were 98 (95% CI = 70-127) 96 (95% CI = 70-123) for asthma and COPD respectively. Among the employed, prevalence ratios for IHD in all but one of the individual occupation groups examined did not differ from the average, however among those not employed the ratio in the all-exposed (PR = 152, 95% CI = 128-174) exceeded that in the controls (PR = 112, 95% CI = 104-120). CONCLUSION: Occupational groups exposed to motor vehicle pollution have a marginally increased prevalence of asthma compared with working males generally, though not compared with occupation matched controls. This study has demonstrated a methodology for using GP data to examine occupation-related disease. This could be used in future by augmenting GP data with occupation and smoking information.

Morbidity and healthcare utilisation of children in households with one adult: comparative observational study.

OBJECTIVE: To identify and consider differences in morbidity in children in households with one adult presenting to general practitioners compared with children in households with more than one adult. DESIGN: Observational study; data analysed with logistic regression controlling for age, sex, and practice. SUBJECTS: 93 356 children aged 0-15 years included in the fourth national study of morbidity in general practice and for whom data about household structure were available. Among them 10 983 (11.8%) were living in households with a sole adult. METHODS: Morbidity data were recorded from each consultation as the assessment diagnosis made by the general practitioner. MAIN OUTCOME MEASURES: Number of consultations and consultations per person for any illness, infections, acute respiratory infections, asthma, and accidents; number presenting and mean consultations per person for immunisation; number receiving home visits and home visits per person visited; average annual frequency of consultation among those consulting. RESULTS: Compared with children in other households, a higher proportion of children in households with one adult consulted for infections and accidents. The proportion consulting for immunisation was lower and the proportion receiving home visits greater. Mean numbers of consultations per person consulting were also generally higher for all conditions. For infections, accidents, and home visits, the differences were evident in all age groups. CONCLUSIONS: The study confirms the importance of single parent families as an indicator of deprivation. Children in such families should be targeted for immunisation and accident prevention.

A physiological classification of viridans streptococci by use of the API-20STREP system.

Physiological reactions of viridans streptococci were examined by the API-20STREP system and a selection of conventional tests. Cluster analysis of these results produced a classification similar to a taxonomic scheme based on that of Colman and Williams. The organisms could be divided into the six recognised species--Streptococcus mutans, S. bovis, S. mitior, S. sanguis, S. salivarius and S. milleri. Analysis confirmed that S. mitior and S. sanguis can be distinguished in the API-20STREP test by hydrolysis of arginine but not by dextran production. Although S. mutans, S. mitior and S. sanguis can be divided into two further subgroups, the taxonomic significance of this is unclear. With this means of classification, most organisms could be identified easily by a small number of tests. API-20STREP is convenient for performing physiological tests on viridans streptococci, but the information provided by the manufacturers in regard to identification and nomenclature is in need of revision.

Hay fever treatments--which should be tried first?

A series of comparative trials on nine popular and pharmacologically distinct regimens for the treatment of hay fever was undertaken in the course of normal general practice in the pollen seasons of 1981-83. One hundred and forty doctors recruited 640 patients to assess the overall usefulness of the treatments on daily diaries. ;Usefulness' was scored on a linear analogue scale weighing up the degree of hay fever symptoms during treatment, side effects and ease of use of the preparation.The regimen with the highest overall usefulness score was beclomethasone diproprionate with sodium cromoglycate eye drops (Beconase and Opticrom). Although the score was not significantly higher than those for methylprednisolone acetate (Depo-Medrone), astemizole (Hismanal) or terfenadine (Triludan), Beconase/Opticrom scored significantly better than mequitazine (Primalan), chlorpheniramine maleate (Piriton), sodium cromoglycate nasal insufflation with xylometazoline/antazoline eye drops (Rynacrom and Otrivine-Antistin) and azatadine maleate (Optimine). Beconase/Opticrom was first in rank order with respect to all the other regimens for the treatment of both mild and severe hay fever. Dimethothiazine (Banistyl), also shown to be useful, has since been withdrawn from prescription.

Unemployment and mortality: a small area analysis.

It has been claimed that unemployment affects the health and thus the mortality of the unemployed, their families, and other members of their communities. This paper examines the relation between mortality and the unemployment experiences of small areas which vary in the extent to which their unemployment levels have changed in recent years. Quarterly numbers of unemployed, classified by age, sex, duration of unemployment, and unemployment office for 1977-81, have been aggregated to correspond to Family Practitioner Committee areas (FPCs), for which population and mortality data had been collected for a different study. There was little variation in long term (greater than 6 months) unemployment trends prior to July 1980, but subsequently there were large variations between FPCs in the rate of increase in unemployment rates. Mortality data for suicide, ischaemic heart disease, cerebrovascular disease, and all causes were examined for the period 1975-83. When the mortality trends of FPCs with different unemployment experiences were compared, no statistically significant differences in trends were found, although areas with greater increases in unemployment appeared to have slightly worse mortality trends for suicide, ischaemic heart disease, cerebrovascular disease, and total mortality for men in the younger age groups. If changes in the level of unemployment do have an effect on changes in trends in mortality levels, this effect is not of sufficient magnitude to be statistically significant with the sample available, in spite of the fact that it included the whole of England and Wales.

Patterns of physicians' use of medical resources in ambulatory settings.

We studied British general practitioners' use of ambulatory resources to determine whether the quantities of different resources used were related to each other, and whether these quantities were associated with their personal characteristics. Rates of laboratory requests, referrals for specialty opinion, prescriptions, and visits per patient per year were examined for 21 physicians in seven practices over one year. Physicians who more frequently saw their patients referred and prescribed for them more often and ordered more tests, once the number of years they had practiced was taken into account. Doctors who ordered more tests referred their patients more frequently, regardless of how often they saw them. Doctors longer in practice saw and prescribed for their patients more frequently. Resource use was not related to other personal characteristics we studied. Greater frequency of patient-physician contact appears to increase costs not only through use of more professional time but also through greater use of other ambulatory resources. Attention to the use of only one type of resource may result in a distorted picture of how physicians care for their patients and the costs that such care incurs.

Area variation in mortality from diseases amenable to medical intervention: the contribution of differences in morbidity.

Several conditions, whose timely and appropriate therapy should decrease case fatality, have been proposed as indicators of medical care quality for the National Health Service. Mortality rates for these diseases vary widely within the UK. To evaluate the contribution of varying incidence rates to these mortality differences, routinely collected morbidity and mortality data for 1974-1978 were analysed for 98 Area Health Authorities (AHAs) in England and Wales. Although differences in morbidity (as measured by hospital discharge and disease registration rates) and socioeconomic factors account for some of the area variation in mortality, significant heterogeneity persists after these factors are taken into account. This finding suggests that morbidity and socioeconomic factors are not the only determinants of mortality variation among areas for these particular diseases. Variation in quality of medical care may account for this result, although regional diagnostic and reporting differences and variation in disease severity among areas must also be considered.

PIP: This study is concerned with variations in mortality from diseases amenable to medical intervention in England and Wales. The focus is on the extent to which these variations can be used to evaluate the quality of medical care provided by the National Health Service. The data concern 98 Area Health Authorities and are for the period 1974-1978. The results suggest that differences in morbidity and socioeconomic factors are not the only determinants of mortality and that variations in the quality of health care may also be relevant factors.

Illness, disability, and drugs among 25 to 75 year olds living at home.

A survey in a London borough showed that 15% of adults living at home were restricted in one or more areas of their lives because of illness. A sample of these adults aged 25 to 75 years was interviewed using a validated medical questionnaire, and the severity of their restrictions was also assessed using a separate instrument. Many symptoms were found which had not been reported to a doctor and many were not being treated. When the disability scores were regressed on symptoms classified as reported to a doctor, unreported, or absent, with a few exceptions it was the reported symptoms that were significantly associated with disability. Similarly, when symptoms were classified as treated (by doctor or respondent), untreated, or absent, treated symptoms were associated with disability. Some disabling symptoms were similar to the effects, mainly adverse, of commonly prescribed drugs, and these symptoms were reported more frequently by respondents taking the possible offending drug than by those not taking the drug. It appears that making general practitioners aware of unreported and untreated symptoms among their 25 to 75 year old patients will not reduce the overall level of disability in the community. However, the iatrogenic component of disability needs to be studied further.

Some international comparisons of mortality amenable to medical intervention.

A series of outcome indicators was proposed for assessing the curative aspects of health care using several diseases for which evidence suggested that death was largely avoidable provided that appropriate medical treatment could be given in time. International data were examined for those causes for which data were readily available. Time trends in mortality were compared for each of these conditions for six countries that had experienced appreciable growth in health services during 1950-80. Mortality from the heterogeneous "avoidable" causes had declined faster than mortality from all other causes in each of the six countries. Despite problems of diagnosis, reporting, and classification of diseases that may have existed among countries, making international comparisons of absolute mortality difficult, the trends of declining mortality were similar, lending credibility to the use of these causes of mortality as indices of health care within countries. Changes within countries may also have been attributable to changes in social, environmental, genetic, and diagnostic factors, which were not examined. Nevertheless, the consistency in mortality trends for this group of "amenable" diseases suggested that improvements in medical care were a factor in their rapid decline.

Psychosocial support and change in the health status of physically disabled people.

Evidence is presented on the relationship between psychosocial support (social contact and emotional intimacy) and changes in health status (physical, psychosocial and emotional functioning) experienced by 583 adults age 45-75 years living at home with a preexisting physical illness. Data were used from a panel study of physically disabled adults in London, England to provide a test of the buffer and direct effects hypotheses concerning social support and adverse life events. Controlling for age, sex and initial level of health status, the analyses showed that a low level of social contact was associated significantly with deterioration in psychosocial and emotional functioning only in the presence of adverse life events. A similar but non-significant pattern existed for physical functioning. A high level of social contact had a more protective effect on the physical functioning of respondents with arthritis or heart trouble who also reported depression, except among women age 45-64. Level of emotional intimacy was not a significant influence on reported health status change. Confiding relationships do not appear important for adults with preexisting illnesses who are not at significant risk of developing stress-related conditions. Social participation outside the home would help to reduce deterioration in psychosocial and emotional functioning, important outcomes for improving and maintaining quality of life.

Case history questionnaires in the study of doctors' use of resources. Are they measuring what we want?

A set of 15 self-administered case histories were developed, each consisting of a short case followed by a standard format on which desired tests were checked. After pilot testing the case histories within a group of doctors, the authors selected the ten cases with the highest item-total correlations that also provided a broad clinical spectrum. Using a different group of 19 doctors, test-ordering on the questionnaire was compared with actual test-ordering in clinical practice. Questionnaire test-ordering did not reflect practice behavior; in fact, the relationship tended to be inverse (r = -0.43: P less than 0.10). Adjusting for case-mix variation by including only those practice cases with diagnoses similar to questionnaire cases did not improve its performance (r = -0.50: P less than 0.05). These findings suggest that test-ordering on case history questionnaires may not reflect actual practice behavior. Conclusions about test-ordering behavior and management strategies to alter it should not be based on results from questionnaires that have not been validated against actual practice.

Is the Jarman underprivileged area score valid?

A recently published validation of an underprivileged area score, which is intended to reflect factors that increase general practice workload or pressure on their services, was incomplete; a validation based on criteria other than the opinion of general practitioners is also required. Areas with higher mortality from diseases where general practitioner intervention can reduce mortality substantially are likely to have a greater need for general practice services. Similarly, the need for general practitioner services should be higher where the incidence of such treatable conditions is higher. This paper describes the association between Jarman's score and (a) mortality from causes that are amenable to general practice intervention and (b) incidence of two diseases where general practice intervention is important. Using these data the score appears to have external criterion validity and thus is likely to reflect, at least crudely, the need for general practitioner services.

A community trial strategy for evaluating treatment for symptomatic conditions.

A method has been developed for simultaneously comparing the usefulness of many treatments of established value for symptomatic medical conditions. Medical assessment of outcome is not employed. Instead patients are required to assess treatments prescribed during the course of ordinary general practice rather than under the strictly controlled settings of most clinical trials. Outcome incorporates patient compliance and treatment acceptability and is based on patients' subjective judgments of the usefulness of randomly allocated treatments as recorded in self-completed diaries, which are mailed directly to a trial centre. Thus large and more representative samples are achieved through minimizing the efforts required, both of participating doctors and of patients. Although the approach was originally developed and tested for the comparison of hay fever treatment regimens, we believe that it can be adapted to compare many other treatments where patient-reported symptoms validly describe the outcome of interest. The feasibility of the approach was tested in two pilot studies, and it has been employed successfully in a two-year trial comparing seven hay fever treatments. Aspects of analysing such trials are discussed.