Do doctors under-provide, over-provide or do both? Exploring the quality of medical treatment in the Philippines.

OBJECTIVE: To assess the quality of medical treatment by disaggregating quality into components that distinguish between insufficient and unnecessary care. DESIGN: Randomly selected doctors were asked how they would treat a sick child. Their responses were disaggregated into how much of an evidence-based essential treatment plan was completed and the number of additional non-essential treatments that were given. Key variables included the expected cost, the health consequences of insufficient and unnecessary care and comparisons between public and private physicians. Responses to 160 clinical performance vignettes (CPVs) were analysed. SETTING: Philippines. PARTICIPANTS: One hundred and forty-three public and private physicians in the Philippines, collected in November 2003-December 2004 and September 2006-June 2007. INTERVENTIONS: CPVs administered to physicians. MAIN OUTCOME MEASURES: Process quality measures (accounting for the possibility of both over-treatment and under-treatment). RESULTS: Based on CPVs, doctors gave both insufficient and unnecessary treatment to under-five children in 69% of cases. Doctors who provided the least sufficient care were also the most likely to give costly or harmful unnecessary care. Insufficient care typically had potentially worse health consequences for the patient than unnecessary care, though unnecessary care remains a concern because of overuse of antibiotics (47%) and unnecessary hospitalization (34%). CONCLUSIONS: Quality of care is complex, but over- and under-treatment coexist and, in our analysis physicians that were more likely to under-treat a sick child were also those more likely to over-treat.

Estimating unreported malaria cases in England: a capture-recapture study.

A capture-recapture study was undertaken to estimate the incidence and likely total burden of malaria cases in England. Cases diagnosed by the national Malaria Reference Laboratory (MRL) between July 2003 and December 2004 were matched with cases reported to Hospital Episode Statistics using demographic, geographical, parasitological, and temporal information. A total of 3861 cases were recorded in one or both datasets; the 'unknown population' was estimated as 746 cases (95% CI 677-822) giving a total of 4607 cases (95% CI 4446-4767) over 18 months. Eighty-four percent (95% CI 83-85) of cases were recorded in one or both datasets. Fifty-six percent (95% CI 54-58) of cases were captured by the MRL surveillance system; ascertainment for Plasmodium falciparum and London cases was higher at 66% and 62%, respectively. Improving case ascertainment will facilitate effective measures to reduce the burden of this preventable disease in the UK.

Neurokinin receptor mRNA localization in human midbrain dopamine neurons.

The structurally related neurokinin peptides, substance P and neurokinin A, are found in abundance within the substantia nigra of a variety of mammalian species. Although it has been established recently that the neurokinin-3 (NK3) receptor is the predominant neurokinin receptor found in rat substantia nigra and adjacent midbrain nuclei, the nature of the neurokinin receptor expressed in human midbrain has not been elucidated. In the present study, neurokinin receptor messenger RNA (mRNA) content within rat and human midbrain were directly compared by using quantitative in situ hybridization histochemistry. In contrast to the high abundance of NK3 receptor mRNA within dopamine (DA) cells of the rat midbrain, neurokinin-1 (NK1), but not NK3, receptor mRNA was localized to human midbrain DA cells. Within the human midbrain, the abundance of NK1 receptor mRNA differed significantly among the distinct DA cell-containing nuclei, with the highest level of expression seen in several subdivisions of the substantia nigra. Thus different neurokinin receptor subtypes apparently mediate the effects of substance P and neurokinin A on human versus rat DA neurons.

Age-related and regional differences in dopamine transporter mRNA expression in human midbrain.

We assessed the abundance of dopamine transporter messenger RNA (DAT mRNA) in various human midbrain dopamine cell groups using in situ hybridization. The youngest individuals studied (17-23 years of age) exhibited significant regional heterogeneity of DAT expression, both in terms of the number of dopamine neurons expressing DAT mRNA and the abundance of DAT mRNA per cell, with the highest levels of expression evident within the ventral tier of the substantia nigra and lowest expression within the retrorubral field. In the older subjects (65-72 years old) analyzed, DAT mRNA in all regions was reduced to the level seen in the retrorubal field, indicating a positive correlation between initial levels of DAT expression and subsequent age-related reductions, with some regions exhibiting up to a 75% loss of DAT mRNA with age. The age-related decline in DAT mRNA was due to both a decrease in the abundance of DAT mRNA per dopamine cell as well as a decrease in the total number of dopamine cells expressing DAT mRNA, although tyrosine hydroxylase expression was less affected. These results indicate that changes in dopamine neurotransmission seen in normal aging may be related to altered DAT gene expression.

Differences in biological risk factors for cardiovascular disease between three ethnic groups in the Whitehall II study.

This study compares risk factors for cardiovascular disease in civil servants of three ethnic groups screened as part of the Whitehall II cohort study. Previously identified risk factors for cardiovascular disease in 360 Afro-Caribbean and 577 South Asian subjects are compared with the 8973 white Caucasian subjects. Controlling for socio-economic status is more precise than in most previous studies of cardiovascular differences between ethnic groups. After controlling for socio-economic confounding factors, age and sex, South Asian subjects were found to have increased prevalence of hypertension (defined as either having systolic pressure of > 160, diastolic pressure of > 95 or being on antihypertensives) OR 2.3 (95% CI 1.6-3.3), diabetes OR 4.2 (95%, CI 3.0-5.8) and a high risk lipid profile, although total cholesterol was lower than in the white population. Afro-Caribbean subjects had more hypertension OR 4.0 (95% CI 2.8-5.7) and diabetes OR 2.8 (95% CI 1.7-4.6), but this was accompanied by a favourable lipid profile with low cholesterol and high HDL. Afro-Caribbean alcohol and smoking habits were low-risk. Socio-economic status was found to be an important confounding factor for ethnic differences in biochemical risk factors for cardiovascular disease. However, adjusting for socioeconomic class only attenuates observed differences; it does not abolish them.

Quantitation, cellular localization and regulation of neurokinin receptor gene expression within the rat substantia nigra.

The diverse biological effects of substance P and related peptides are mediated by multiple neurokinin receptors. The CNS sites of neurokinin receptor biosynthesis have not been fully elucidated and little is known about the regulation of neurokinin receptor gene expression. In the present study, the abundance of neurokinin-1, neurokinin-2 and neurokinin-3 receptor messenger RNAs in various rat brain regions was quantitated using a sensitive solution hybridization assay. Midbrain neurokinin receptor gene expression was then examined in detail. In situ hybridization experiments localized high levels of neurokinin-3 receptor messenger RNA to presumptive dopamine neurons, as evidenced by sensitivity to 6-hydroxydopamine lesions and the presence of tyrosine hydroxylase messenger RNA in serial sections. Lesions of nigral afferent (including substance P-containing) pathways from the caudate-putamen increased both nigral neurokinin-3 and neurokinin-1 receptor messenger RNA levels two- to three-fold. These data provide the anatomical substrate for physiological data suggesting that substance P (released from striatonigral neurons) may act on nigral cells through neurokinin-1 receptors, while the substance P co-transmitter neurokinin A may act preferentially on dopamine neurons through neurokinin-3 receptors. The magnitude of denervation-induced changes in neurokinin receptor messenger RNAs suggests significant plasticity of neurokinin receptor gene expression.

Impact of community-based mass treatment for trachoma with oral azithromycin on general morbidity in Gambian children.

BACKGROUND: The World Health Organization has recently targeted the elimination of trachoma as a public health problem by the year 2020. Community-based treatment with antibiotics, including oral azithromycin, is recommended for severely affected communities. The incidence of adverse effects after azithromycin treatment is not known in trachoma endemic communities. METHODS: We compared the effects of azithromycin with those of topical tetracycline given as mass treatment for trachoma on childhood morbidity in eight rural Gambian villages. The entire population of four villages received oral azithromycin suspension (Zithromax, Pfizer) in doses of 20 mg/kg on Days 1, 8 and 15; the other four villages received topical tetracycline eye ointment for 42 days. Morbidity surveys of subjects 3 months to 14 years old were conducted on Days 0, 7, 14, 21 and 28. RESULTS: Of the 804 subjects recruited complete follow-up data were available on 791 (412 azithromycin, 379 tetracycline). Fever and headache were the most common complaints. Apart from cough other symptoms were equally prevalent in both groups at baseline. The azithromycin group had 20% fewer illness, fever and headache episodes and 40% fewer diarrhea and vomiting episodes at follow-up than did the tetracycline group. CONCLUSIONS: Azithromycin treatment for trachoma had favorable short term effects on childhood morbidity in rural Gambian villages, particularly in the high malaria transmission season, and adverse effects were not a problem.

GABA transporter mRNA: in vitro expression and quantitation in neonatal rat and postmortem human brain.

A previously isolated rat cDNA clone encoding the membrane transporter for the neurotransmitter gamma-aminobutyric acid was expressed in transfected COS cells. The resultant transporter protein was characterized kinetically and pharmacologically. The apparent Kt (6.1 microM) and the pharmacological profile of a neuronal-type transporter observed in these mammalian cells were consistent with previous data obtained in Xenopus laevis oocytes. Post-natal levels of gamma-aminobutyric acid transporter mRNA in rat cerebellum, cerebral cortex and striatum (as measured by nuclease protection assay) transiently exceeded levels present in the adult brain. Human gamma-aminobutyric acid transporter mRNA also was measured by nuclease protection assay using as probe a human transporter cDNA homolog obtained by polymerase chain reaction. These studies suggest that quantitation of rat and human gamma-aminobutyric acid transporter mRNAs may provide a useful index of transporter gene expression.

Serological speciation of human schistosome infections by ELISA with a panel of three antigens.

AIMS: To find out whether serology can reliably speciate human schistosomiasis using a simple enzyme linked immunosorbent assay (ELISA) technique. METHODS: Stored sera from 66 patients with microscopically confirmed schistosomiasis were subjected to ELISA using a panel of three antigens, namely: unfractionated Schistosoma mansoni soluble egg antigen (SEA); CEF6, a cationic fraction of SEA; and crude S margrebowiei egg antigen, prepared from an animal schistosome closely related to S haematobium. RESULTS: The optical densities (ODs) obtained using CEF6 as antigen were significantly higher in sera from S mansoni infected patients than in sera from S haematobium infected patients (median OD, 0.810 v 0.595). Using S margrebowiei egg antigen, the optical densities were significantly higher in S haematobium sera than in S mansoni sera (median OD, 0.794 v 0.544). There was no significant difference in optical densities between S mansoni and S haematobium sera using SEA (median OD, 0.725 v 0.737). The ratio of ODs (CEF6 to S margrebowiei egg antigen) was calculated: a ratio of >1 indicated S mansoni infection (sensitivity, 88%) and a ratio of <1 indicated S haematobium infection (sensitivity, 84%). The odds ratio for S haematobium having an OD ratio of <1 was 36.8 (95% confidence interval, 7.0 to 194). CONCLUSIONS: The identity of the infecting species of schistosome can be determined using the panel of antigens described. SEA should be used to screen serum samples, and the CEF6 : S margrebowiei egg antigen ELISA optical density ratio can be used where serological speciation is required.

Falciparum malaria in malaria-naive travellers and African visitors.

BACKGROUND: Patients from malaria-endemic areas who present in non-endemic countries with Plasmodium falciparum malaria are often assumed to have some degree of immunity. If this were reliably true, it would simplify their management. AIM: To determine whether being born and resident in a malaria-endemic country is a predictor of clinical course in UK admissions for malaria. DESIGN: Prospective observational study. METHODS: We compared clinical and laboratory parameters between two groups of adult patients with acute P. falciparum malaria, admitted to the Hospital for Tropical Diseases in London: one born and resident in non-endemic countries (n=167); the other born and resident in malaria-endemic countries of Africa (n=93). Patients were excluded if they had taken prophylaxis or prior treatment. RESULTS: There were no differences between these two groups in terms of peak parasitaemia or time to parasite clearance. There was a significantly higher risk of malaria-naive patients having peak parasitaemia >5% (OR 4.5, 95%CI 1.5-13.2). Of those usually resident in Africa, 31% required parenteral treatment compared to 41% of the malaria-naive group. Of the visitors from Africa, 4.3% needed admission to the Intensive Therapy Unit (ITU), although there was a tendency for more malaria-naive patients to require ITU care (OR 2.69, 95%CI 0.9-8.1). DISCUSSION: While there are differences in presentation between those who are malaria-naive and those who live in malaria-endemic African countries, making assumptions about the immunity or clinical course of an individual patient with malaria presenting in the UK on the basis of presumed history of exposure is unwise.

Neurokinin-3 receptors modulate dopamine cell function and alter the effects of 6-hydroxydopamine.

Neurokinin-3 receptor expression within rat midbrain dopamine neurons was demonstrated using a combination of in situ hybridization and receptor autoradiographic techniques. Continuous intranigral infusion of the neurokinin-3 receptor agonist senktide selectively increased striatal dopamine metabolism over a period of several days, followed by apparent development of tolerance. In contrast, in animals with moderate unilateral 6-hydroxydopamine-induced lesions of nigrostriatal dopamine cells, intranigral senktide infusion increased dopamine turnover in the surviving dopamine neurons and reduced functional dopamine asymmetry (reflected by spontaneous rotations) over the 2-week period tested. Thus nigral neurokinin receptors can modulate normal dopamine cell activity and may provide a therapeutic target in the treatment of Parkinson's disease.

Mortality rates and recurrent rates of tuberculosis in patients with smear-negative pulmonary tuberculosis and tuberculous pleural effusion who have completed treatment.

SETTING: Queen Elizabeth Central Hospital, Blantyre, and Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To follow-up human immunodeficiency virus (HIV) seropositive and HIV-seronegative patients with smear-negative pulmonary tuberculosis (PTB) and pleural TB who had completed treatment with two different regimens in Blantyre and Zomba, and to assess rates of mortality and recurrent TB. DESIGN: Patients with smear-negative and pleural TB who had completed 8 months ambulatory treatment in Blantyre or 12 months standard treatment in Zomba and who were smear and culture negative for acid-fast bacilli at the completion of treatment were actively followed every 4 months for a total of 20 months. RESULTS: Of 248 patients, 150 with smear-negative PTB and 98 with pleural TB, who completed treatment and were enrolled, 205 (83%) were HIV-positive. At 20 months, 145 (58%) patients were alive, 85 (34%) had died and 18 (7%) had transferred out of the district. The mortality rate was 25.7 per 100 person-years, with increased rates strongly associated with HIV infection and age >45 years. Forty-nine patients developed recurrent TB. The recurrence rate of TB was 16.1 per 100 person-years, with increased rates strongly associated with HIV infection, having smear-negative PTB and having received 'standard treatment'. CONCLUSION: High rates of mortality and recurrent TB were found in patients with smear-negative PTB and pleural effusion during 20 months of follow-up. TB programmes in sub-Saharan Africa must consider appropriate interventions, such as co-trimoxazole and secondary isoniazid prophylaxis, to reduce these adverse outcomes.

'Smear-negative' pulmonary tuberculosis in a DOTS programme: poor outcomes in an area of high HIV seroprevalence.

SETTING: Lilongwe Central Hospital, Malawi. OBJECTIVES: To investigate 1) treatment outcome of a cohort of smear-negative pulmonary TB (snPTB) patients in an area of high human immunodeficiency virus (HIV) seroprevalence, and 2) whether poor treatment outcomes are due to non-TB patients being mistakenly treated for TB due to lack of diagnostic facilities. DESIGN: Patients about to be registered for snPTB treatment by the National TB Programme underwent further assessment including TB culture, bronchoscopy and bronchoalveolar lavage. All patients were followed up for 8 months. Standard TB control treatment outcomes were recorded. RESULTS: Of 352 snPTB patients assessed, 137 patients had bacteriologically confirmed TB, 136 had possible TB, and 79 had other non-TB diagnoses. The HIV seroprevalence rate was 89%. Outcomes were known for 325 (92%) patients: 129 (40%) died within 8 months. Death rates on TB treatment were 31% for bacteriologically confirmed TB patients and 35% for patients with possible TB but no bacteriological diagnosis. The death rate among patients with non-TB diagnoses was 53%. HIV infection significantly increased the risk of death (OR 3.9; P = 0.01). CONCLUSION: SnPTB is strongly associated with HIV infection in Malawi, where patients treated for snPTB have a poor prognosis. The high mortality is not fully explained by non-TB patients being mistakenly treated for TB.

Neurotrophic effects of substance P on hippocampal neurons in vitro.

The potential neurotrophic effect of substance P-like immunoreactivity present in culture media was assessed in rat embryonic day 18 hippocampal cultures. The neurokinin-1 (substance P) receptor antagonist CP-96345 induced neurotoxicity that was dose dependent and attenuated by addition of substance P or the neurokinin-1 agonist [Sar9,Met(O2)11]-SP. These studies suggest that under some conditions neurokinin-1 receptor stimulation promotes neuronal survival.

Presentation and outcome of 1107 cases of schistosomiasis from Africa diagnosed in a non-endemic country.

Schistosomiasis is found in a significant proportion of returning travellers and immigrants to Britain. This study is a retrospective review of 1107 consecutive cases of schistosomiasis from Africa diagnosed by microscopy or serology presenting to the Hospital for Tropical Diseases, London, UK. 50.4% of cases were asymptomatic. The most common symptom which resolved on treatment was tiredness. Serology was positive in 951 (86%), and ova seen in 45%. Urine dipstick testing was positive for blood in 21% and protein in 15%, with eosinophilia in 44%. In this population urine dipstick, full blood count and serology were all insufficient screening tools used alone. Among patients with full follow-up data 3 months or more after treatment with praziquantel, definite treatment failure occured in 4 of 271 (1.5%), restricting the analysis to those with ova seen at diagnosis. There was no significant difference in treatment failure between 1 and 3 days of treatment. Antibody level was the same or higher than at treatment in 55% of cases seen after about 3 months and 38% after 1 year, confirming it is probably of limited clinical use in detecting treatment failure.

High mortality rates in tuberculosis patients in Zomba Hospital, Malawi, during 32 months of follow-up.

There is little information about long-term follow-up in patients with smear-negative pulmonary tuberculosis (PTB) or extrapulmonary tuberculosis (EPTB) who have been treated under routine programme conditions in sub-Saharan Africa. A prospective study was carried out to determine outcome 32 months from start of treatment in an unselected cohort of 827 adults TB inpatients registered at Zomba Hospital, Malawi, in 1 July-31 December 1995. By 32 months, 351 (42%) patients had died. Death rates were 30% (95% confidence interval [95% CI] 25-35%) in 386 patients with smear-positive PTB, 60% (95% CI 53-67%) in 211 patients with smear-negative PTB and 47% (95% CI 40-54%) in 230 patients with EPTB. Of the 793 patients with concordant HIV test results 612 (77%) were HIV seropositive: 47% HIV-positive patients were dead by 32 months compared with 27% HIV-negative patients (adjusted hazard ratio [HR] 2.3; 95% CI 1.7-3.1, P < 0.001). Smear-negative PTB patients had the highest death rates during the 32-month follow-up (HR 2.7; 95% CI 2.1-3.5, P < 0.001 compared to smear-positive patients), followed by EPTB patients (HR 1.9; 95% CI 1.5-2.5, P < 0.001 compared to smear-positive patients). When analysis was restricted to after the treatment period had finished (i.e., months 12-32), the differences in mortality were maintained for HIV-serostatus and for types of TB. Low-cost, easy to implement strategies for reducing mortality in HIV-positive TB patients in sub-Saharan Africa (such as the use of trimethoprim-sulphamethoxazole prophylaxis) need to be tested urgently in programme settings.

Investigation of tropical eosinophilia; assessing a strategy based on geographical area.

OBJECTIVES: Patients with eosinophilia are an important clinical problem. This study aimed to assess the most efficient manner of investigating patients with peripheral eosinophilia (eosinophil count >0.5x10(9)ml(-1)) presenting from the tropics. METHODS: Patients attending the Hospital for Tropical Diseases, London, from October 1997 to March 2002 for investigation of eosinophilia were identified prospectively. Laboratory, clinical and demographic data were recorded from laboratory and clinical records. An investigation set was proposed prospectively and assessed for all geographical areas (stool microscopy, strongyloides culture and serology), all of Africa (additional schistosomal serology, terminal urine microscopy and filarial serology) and West Africa (additional day-bloods for microfilaria). RESULTS: Data was analysed for 261 patients. At least one helminthic cause for eosinophilia was found in 64% of patients (median eosinophilia 1.2x10(9)ml(-1)). Seventeen per cent of patients had more than one helminth species found. Median eosinophilia increased with number of diagnoses per patient. The proposed investigation sets were validated, with high yield for all proposed tests apart from filarial serology outside West Africa, and good sensitivity. CONCLUSIONS: Initial investigation of eosinophilia in patients presenting from the tropics may be guided by a simple investigation set depending on broad area of travel which has high sensitivity and yield. Patients frequently have more than one helminthic cause of eosinophilia.

Psychosocial risk factors for coronary disease in White, South Asian and Afro-Caribbean civil servants: the Whitehall II study.

BACKGROUND: Psychosocial factors are associated with the etiology and prognosis of coronary heart disease (CHD) in White populations; however, previous studies have not examined the distribution of psychosocial factors in ethnic groups with coronary rates higher (South Asian) and lower (Afro-Caribbean) than those of Whites. STUDY OBJECTIVE: To determine whether ethnic differences in psychosocial risk factors parallel those in CHD mortality. DESIGN: Cross-sectional survey. SETTING: 20 civil service departments in London. PARTICIPANTS: 8973 White, 577 South Asian, and 360 Afro-Caribbean office-based civil servants, aged 35-55 years. OUTCOME MEASURES: Minor psychiatric morbidity (General Health Questionnaire), social supports (marital status, social networks, negative aspects of support, confiding/emotional support, social support at work), psychosocial work characteristics (job control, effort-reward imbalance), hostility levels and presence of Type A personality. RESULTS: South Asians, compared to Whites, had more depression, higher negative supports, less social support at work, less job control, more effort-reward imbalance and higher levels of hostility, when adjusting for age and sex. Afro-Caribbeans, compared to Whites, had lower minor psychiatric morbidity and lower Type A scores. The remaining psychosocial factors showed either no ethnic differences in distribution, or differences contrary to those predicted from coronary event rates. Adjustment for employment grade made little difference to these associations. CONCLUSION: Among South Asians, the majority of whom were Indian, the distribution of psychosocial factors was consistent with ethnic differences in coronary rates; the pattern for Afro-Caribbeans was less consistent. Further research is required to test the extent to which psychosocial factors predict coronary events within ethnic groups and to characterize better psychosocial measures.

Malaria at Christmas: risks of prophylaxis versus risks of malaria.

PIP: A large increase in the number of falciparum malaria cases imported into the UK was reported to the malaria reference laboratory in the first quarter of 1998. Contributory factors were unusually heavy rains in east Africa and a reduction in the use of the most effective antimalarial drug, mefloquine. There was also an increase in the number of cases of severe malaria in the UK. During December 1997 and January 1998, the Hospital for Tropical Diseases, London, treated 5 patients for severe malaria and gave advice on 20 more patients with malaria who had been admitted to intensive care units throughout England. 4 of the severe cases treated at the hospital are reported. In 3 of those 4 cases, incorrect, misleading, or inadequate advice was given by health care professionals. Media coverage of the adverse effects of antimalarial drugs has contributed to confusion about prophylactic regimens among both health care professionals and the public. The incidence of falciparum malaria among travellers who do not take prophylactic drugs is about 0.6% in east Africa and 3.5% in west Africa over a 2-week travel period. Travellers need to take measures to avoid being bitten by mosquitoes and should be taught to promptly seek medical help if they develop a fever while abroad or after they return. Moreover, using any one of the recommended prophylactic regimens is better than not using a potent regimen or no prophylaxis at all. Mefloquine is 90% protective against malaria in sub-Saharan Africa. While the efficacy of proguanil and chloroquine in 1987 was about 70% in west Africa and 50% in east Africa, those levels are now probably lower. The side effects of antimalarial drugs are discussed.^ieng

Investigating eosinophilia in patients returned from the tropics.

In patients who have returned from the tropics, eosinophilia usually signifies infection with worms. This paper gives an approach to investigating these patients systematically. The key element is a good travel history leading to targeted investigations.