Amoxicillin plus temocillin as an alternative empiric therapy for the treatment of severe hospital-acquired pneumonia: results from a retrospective audit.

A formulary decision was made at a large provider of acute hospital services in Surrey to replace piperacillin/tazobactam with amoxicillin+temocillin for the empiric treatment of severe hospital-acquired pneumonia. This decision was made because the use of broad-spectrum-ß-lactam antibiotics is a known risk factor for Clostridium difficile infection (CDI) and for the selection of resistance. After the antibiotic formulary was changed, a retrospective audit was conducted to assess the effect of this change. Data from patients hospitalised between January 2011 and July 2012 for severe hospital-acquired pneumonia and treated empirically with piperacillin/tazobactam or amoxicillin+temocillin were reviewed retrospectively. Clinical characteristics of patients, data related to the episode of pneumonia, clinical success and incidence of significant diarrhoea and CDI were analysed. One hundred ninety-two episodes of severe hospital-acquired pneumonia in 188 patients were identified from hospital records. Ninety-eight patients received piperacillin/tazobactam and 94 amoxicillin+temocillin. At baseline, the two treatment groups were comparable, except that more patients with renal insufficiency were treated with piperacillin/tazobactam. Clinical success was comparable (80 versus 82 %; P = 0.86), but differences were observed between piperacillin/tazobactam and amoxicillin+temocillin for the rates of significant diarrhoea (34 versus 4 %, respectively; P < 0.0001) and for CDI (7 versus 0 %, respectively; P < 0.0028). This preliminary study suggests that the combination amoxicillin+temocillin is a viable alternative to piperacillin/tazobactam for the treatment of severe hospital-acquired pneumonia. This combination appears to be associated with fewer gastrointestinal adverse events. Further studies are needed to evaluate the place of amoxicillin+temocillin as empiric treatment of severe hospital-acquired pneumonia.

Distance to health services and treatment-seeking for depressive symptoms in rural India: a repeated cross-sectional study.

AIMS: Research from high-income countries has implicated travel distance to mental health services as an important factor influencing treatment-seeking for mental disorders. This study aimed to test the extent to which travel distance to the nearest depression treatment provider is associated with treatment-seeking for depression in rural India. METHODS: We used data from a population-based survey of adults with probable depression (n = 568), and calculated travel distance from households to the nearest public depression treatment provider with network analysis using Geographic Information Systems (GIS). We tested the association between travel distance to the nearest public depression treatment provider and 12 month self-reported use of services for depression. RESULTS: We found no association between travel distance and the probability of seeking treatment for depression (OR 1.00, 95% CI 0.98-1.02, p = 0.78). Those living in the immediate vicinity of public depression treatment providers were just as unlikely to seek treatment as those living 20 km or more away by road. There was evidence of interaction effects by caste, employment status and perceived need for health care, but these effect sizes were generally small. CONCLUSIONS: Geographic accessibility - as measured by travel distance - is not the primary barrier to seeking treatment for depression in rural India. Reducing travel distance to public mental health services will not of itself reduce the depression treatment gap for depression, at least in this setting, and decisions about the best platform to deliver mental health services should not be made on this basis.

Drug-resistant tuberculosis patient care journeys in South Africa: a pilot study using routine laboratory data.

SETTING: Thirteen districts in Eastern Cape (EC), KwaZulu-Natal (KZN) and Western Cape (WC) Provinces, South Africa.OBJECTIVE: To pilot a methodology for describing and visualising healthcare journeys among drug-resistant tuberculosis (DR-TB) patients using routine laboratory records.DESIGN: Laboratory records were obtained for 195 patients with laboratory-detected rifampicin-resistant TB (RR-TB) during July-September 2016. Health facility visits identified from these data were plotted to visualise patient healthcare journeys. Data were verified by facility visits.RESULTS: In the 9 months after the index RR-TB sample was collected, patients visited a mean of 2.3 health facilities (95% CI 2.1-2.6), with 9% visiting ≥4 facilities. The median distance travelled by patients from rural areas (116 km, interquartile range [IQR] 50-290) was greater than for urban patients (51 km, IQR 9-140). A median of 21% of patient's time was spent under the care of primary healthcare facilities: this was respectively 6%, 37% and 39% in KZN, EC and WC. Journey patterns were generally similar within districts. Some reflected a semi-centralised model of care where patients were referred to regional hospitals; other journeys showed greater involvement of primary care.CONCLUSION: Routine laboratory data can be used to explore DR-TB patient healthcare journeys and show how the use of healthcare services for DR-TB varies in different settings.

Multidisciplinary research in public health: a case study of research on access to green space.

OBJECTIVES: Quantitative analysis of the physical and demographic parameters of access to Thames Chase Community Forest (TCCF), and how these have changed between 1990 and 2003; and qualitative exploration of our understanding of the links between health and the natural environment (TCCF), with a focus on the issue of 'access' to green space. STUDY DESIGN: Multimethod design involving both quantitative (analysis of physical access to green space) and qualitative (ethnography) components. METHODS: Quantitative analysis, using geographical information systems, of physical access to the community forest; and ethnographic research including participant observation, non-participant observation, in-depth interviews and attendance at meetings and conferences. RESULTS: The quantitative analysis showed that public access to green space improved between 1990 and 2003 as a result of the regeneration and acquisition of new areas, and the average reduction in distance to green space was 162 m. However, such improvements were distributed differentially between population groups. In both 1990 and 2003, people from deprived areas and in poorer health had better access to green space than people from less deprived areas, but the greatest improvement in access to green space over this interval occurred in areas of below average deprivation (i.e. in the more affluent areas). The ethnographic research showed different interpretations of the notion of access. Use of TCCF was determined by a variety of factors including whether a person could 'imagine themselves' using such a space, different perceptions of what is actually being accessed (e.g. a place to exercise or a place to socialise), and ideas about using the countryside 'properly'. CONCLUSIONS: The health benefits of using a green space, such as TCCF, for walking or exercising are well recognized. However, whether people choose to use local green space may be determined by a variety of factors. These are likely to include physical distance to access of green space, as well as perceptions and understandings of what is being accessed and how it should be used. This study has also illustrated the ways in which multiple methods can be integrated in public health research, and the merits of different approaches to undertaking multidisciplinary work of this type.

Homozygous deletions at 3p12 in breast and lung cancer.

We have constructed a physical map of the region homozygously deleted in the U2020 cell line at 3p12, including the location of putative CpG islands. Adjacent to one of these islands, we have identified and cloned a new gene (DUTT1) and used probes from this gene to detect two other homozygous deletions occurring in lung and breast carcinomas: the smallest deletion is within the gene itself and would result in a truncated protein. The DUTT1 gene is a member of the neural cell adhesion molecule family, although its widespread expression suggests it plays a less specialized role compared to other members of the family.

Area deprivation, social class, and quality of life among people aged 75 years and over in Britain.

BACKGROUND: There is a shortage of research studies that assess how selected characteristics of neighbourhood and personal social circumstances contribute towards health-related quality of life (QoL) among older people. METHODS: Analysis of baseline data for 5581 people aged > or =75 years and over from the Trial of Assessment and Management of Older People in the Community. The scores for four dimensions from the UK version of the Sickness Impact Profile and for the Philadelphia Geriatric Morale Scale were analysed in relation to individual social class and the Carstairs score of socioeconomic deprivation for the enumeration district of residence. RESULTS: In age and sex adjusted analyses, the proportion of participants of social class IV/V living in the most deprived areas who were in the quintile with worst QoL scores was more than double that among those from social class I/II living in the least deprived areas. Individual social class and area deprivation score contributed roughly equally to this doubling for home management, self-care and social interaction, whereas social class appeared a stronger determinant for mobility. Adjustment for living circumstances, health symptoms, and health behaviours substantially reduced the excess risk associated with social class and area deprivation. Being in a rural area was associated with lower risk of poor morale. CONCLUSION: Poor socioeconomic characteristics of both the area and the individual are associated with worse functioning (QoL) of older people in the community. This is not fully explained by health status. Policy should consider community-level interventions as well as those directed at individuals.

A Gla domain mutation (Arg 15-->Trp) in the protein C (PROC) gene causing type 2 protein C deficiency and recurrent venous thrombosis.

A heterozygous CGG-->TGG (Arg 15-->Trp) substitution was detected in a family with inherited type II protein C deficiency and recurrent venous thrombosis. The mutation, which co-segregates with the deficiency state, occurs in a conserved pentapeptide within the gamma-carboxyglutamic acid (Gla) domain of the protein.

Inequalities in availability of National Health Service general dental practitioners in England and Wales.

AIM: To model the inequalities in availability of National Health Service general dental practitioners in England and Wales in relation to key socio-demographic factors. METHODS: Current estimates of the numbers of NHS general dental practitioners for each health authority were related to data from the 1991 census using Poisson regression models, and generalised estimating equations to allow for correlation between results for neighbouring health authorities. RESULTS: An 'average' health authority, without a dental school, would be expected to have 2,138 residents for every NHS dentist. Controlling for relevant factors, health authorities with higher proportions of the following are associated with lower (better) population to dentist ratios by the amounts shown: each 1% higher female population (-11.8%; 95%CI -19.1%, -3.9% P = 0.004); each 1% greater South Asian population (-1.4%; 95%CI -2.1%, -0.7% P <0.001). A health authority with a dental school is associated with a more favourable ratio compared with one without such a facility (-9.2%; 95%CI -16.2%, -1.6% P = 0.019). Each additional 1% of the following are associated with a worse ratio by the amounts shown: children aged 0 to 14 years old (+5.2%; 95% CI +2.4%, +8.1% P < 0.001); adults aged over 65 years old (+2.8%, 95%CI +1.0%, +4.7% P =0.002); households without a car (+0.8%; 95%CI 0.0%, +1.6% P =0.042). CONCLUSIONS: Ensuring access to dental care may be a more complex issue than simply providing adequate numbers of dentists at a national level. Any manpower planning exercise should additionally consider local factors that may act as incentives or disincentives to those professionals who provide care.

Comparison of case fatality in south Asian and white patients after acute myocardial infarction: observational study.

OBJECTIVE: To compare mortality in south Asian (Indian, Pakistani, and Bangladeshi) and white patients in the six months after hospital admission for acute myocardial infarction. DESIGN: Observational study. SETTING: District general hospital in east London. PATIENTS: 149 south Asian and 313 white patients aged < 65 years admitted to the coronary care unit with acute myocardial infarction from 1 December 1988 to 31 December 1992. MAIN OUTCOME MEASURE: All cause mortality in the first six months after myocardial infarction. RESULTS: The admission rate in the south Asians was estimated to be 2.04 times that in the white patients. Most aspects of treatment were similar in the two groups, except that a higher proportion of the south Asians received thrombolytic drugs (81.2% v 73.8%). After adjustment for age, sex, previous myocardial infarction, and treatment with thrombolysis or aspirin, or both, the south Asians had a poorer survival over the six months from myocardial infarction (hazard ratio 2.02 (95% confidence interval 1.14 to 3.56), P = 0.018), but a substantially higher proportion were diabetic (38% v 11%, P < 0.001), and additional adjustment for diabetes removed much of their excess risk (adjusted hazard ratio 1.26 (0.68 to 2.33), P = 0.47). CONCLUSION: South Asian patients had a higher risk of admission with myocardial infarction and a higher risk of death over the ensuing six months than the white patients. The higher case fatality among the south Asians, largely attributable to diabetes, may contribute to the increased risk of death from coronary heart disease in south Asians living in Britain.

Clostridium difficile toxic megacolon following splenectomy.

A case of toxic megacolon following splenectomy for lymphoma is presented. The aetiology of Clostridial difficile infection is reviewed and the hazards of perioperative prohylactic antibiotics are discussed.

Serious injuries in children: variation by area deprivation and settlement type.

OBJECTIVE: To examine the variation in serious injuries in children by the level of deprivation in an area and by types of settlement. METHODS: Hospital admission rates for serious injury to children aged 0-15 years in census lower super output areas in England during the 5-year period 1 April 1999 to 31 March 2004 were analysed. RESULTS: Rates of serious injury in children were higher in the most deprived areas than in the least deprived for pedestrians (rate ratio (RR) 4.1; 95% CI 2.8 to 6.0) and cyclists (RR 3.0; 95% CI 1.9 to 4.7). Rates of serious pedestrian injury were lower in towns and fringe areas (RR 0.67; 95% CI 0.53 to 0.86) and in village (RR 0.64; 95% CI 0.50 to 0.83) areas than in urban areas. The rate of serious injury to cyclists was lower in London than other urban areas (RR 0.78; 95% CI 0.62 to 0.98). The rate of serious injury to car occupants was higher in village than urban areas (RR 1.51; 95% CI 1.05 to 2.17). Rates of serious injury caused by falls were higher in London (RR 1.60; 95% CI 1.47 to 1.75) and lower in villages (RR 0.76; 95% CI 0.66 to 0.88) than in urban areas. Steeper socio-economic gradients in serious injury rates were identified in rural areas for cyclists and for children suffering falls. CONCLUSIONS: Socio-economic inequalities in serious injury exist across the whole of England, particularly for child pedestrians. Rates of serious injury vary by settlement type, and inequalities vary by cause of injury between rural and urban settings.

Fine structure mapping and complementation studies of the metD methionine transport system in Salmonella typhimurium.

A fine structure deletion map of the metD region of the chromosome of Salmonella typhimurium responsible for a high-affinity methionine transport system has been constructed. Complementation tests involving the introduction of metD+DNA contained in a pUC8 vector into metD strains indicated the presence of four complementation groups in the metD region. This suggested that the methionine system belongs to the osmotic shock-sensitive class of transport system, and therefore should possess a periplasmic methionine-binding protein and several membrane proteins. But a deletion mutation covering all known metD point mutations did not affect the level of a methionine binding activity in osmotic shock fluids, suggesting either that the deletion did not extend into the gene encoding the binding protein, or that the binding activity is not associated with the metD system. Possible reasons for the failure to isolate mutations in the gene for the binding protein are discussed.

Perinatal mortality in an English health region: geographical distribution and association with socio-economic factors.

Although the international and regional variability of perinatal mortality rates have been widely studied, less is known about the variability at the small-area level. The geographical distribution of perinatal mortality in the former North-West Thames Health Region, England, during 1981-90, and its association with small-area socio-economic factors, as measured by the Carstairs index of deprivation, were studied. Recently developed methods of analysis, including use of Bayesian statistics, were applied to obtain descriptive results and maps, and for fitting regression models that allowed for the presence of unmeasured risk factors. Significant heterogeneity (P < 0.001) of perinatal mortality across census wards and districts was found. The 5% of wards with the highest mortality experienced a risk more than 1.7 times that of the 5% with lowest mortality. Significant, positive association between deprivation and perinatal mortality was also found. Assuming causality, social differentials at the small-area level accounted for between 1.3% and 14.1% of all perinatal deaths, depending on which level of the Carstairs index was selected as reference. Although a proportion of such variability might be explained by social characteristics, a better understanding of the nature of the association is necessary.

A novel homozygous missense mutation in the protein C (PROC) gene causing recurrent venous thrombosis.

A novel homozygous CCC----CTC (Pro 247----Leu) substitution was detected in the protein C genes of a patient, born to consanguineous parents, with inherited type 1 protein C deficiency and recurrent venous thrombosis. Since one of four heterozygous relatives was also clinically affected, the condition appears to be inherited as an incompletely recessive trait in this family.

Two different missense mutations at Arg 178 of the protein C (PROC) gene causing recurrent venous thrombosis.

Non-identical missense mutations were identified at Arg 178 in the protein C genes of two patients with heterozygous type 1 protein C deficiency and recurrent venous thrombosis.

Selection of an antibody-free population of spermatozoa from semen samples of men suffering from immunological infertility.

Ejaculates from infertile men with significant levels of antisperm antibodies were processed in vitro, in an attempt to prepare sub-populations of antibody-free spermatozoa. Semen samples were processed on a discontinuous Percoll gradient and the resultant sperm preparation was treated with immunobeads. Selection of antibody-free spermatozoa was achieved: less than 10% of the resulting spermatozoa showed binding to immunobeads after treatment in all cases investigated. The overnight survival of these antibody-free spermatozoa was comparable to, or better than, that of the untreated antibody-coated sample obtained from the Percoll gradient. The fertility potential of these treated spermatozoa is currently under investigation.