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Objective\ud \ud Evaluate the capacity of government-run hospitals in Bangladesh to provide emergency and essential surgical, obstetric and anaesthetic services.\ud \ud Methods\ud \ud Cross-sectional survey of 240 Bangladeshi Government healthcare facilities using the World Health Organisation Situational Analysis Tool to Assess Emergency and Essential Surgical Care (SAT). This tool evaluates the ability of a healthcare facility to provide basic surgical, obstetric and anaesthetic care based on 108 queries that detail the infrastructure and population demographics, human resources, surgical interventions and reason for referral, and available surgical equipment and supplies. For this survey, the Bangladeshi Ministry of Health sent the SAT to sub-district, district/general and teaching hospitals throughout the country in April 2013.\ud \ud Results\ud \ud Responses were received from 240 healthcare facilities (49.5% response rate): 218 sub-district and 22 district/general hospitals. At the sub-district level, caesarean section was offered by 55% of facilities, laparotomy by 7% and open fracture repair by 8%. At the district/general hospital level, 95% offered caesarean section, 86% offered laparotomy and 77% offered open fracture treatment. Availability of anaesthesia services, general equipment and supplies reflected this trend, where district/general hospitals were better equipped than sub-district hospitals, though equipment and infrastructure shortages persist.\ud \ud Conclusion\ud \ud There has been overall impressive progress by the Bangladeshi Government in providing essential surgical services. Areas for improvement remain across all key areas, including infrastructure, human resources, surgical interventions offered and available equipment. Investment in surgical services offers a cost-effective opportunity to continue to improve the health of the Bangladeshi population and move the country towards universal healthcare coverage.

Background Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied. Methods We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration

A total of 44 thermally injured children (22 boys and 22 girls), currently aged 11-16 years old, who had been injured 3-14 years previously, stratified by age, sex, degree of burn (1-9%, 10-19%, 20%+) and position of burn (those whose burns included the face and those not burned facially) were selected from a sample pool of 394 previously hospitalized cases. Extent of psychological disturbance experienced by thermally injured adolescents and their mothers indicated that significant effects were evident regarding the sex of the child, age at the time of burn, stage of adolescence, intelligence and by the position and degree of burn.

The psychological effects of thermal injury and children and their mothers were investigated in a three-part study; Part 1 is concerned with group comparisons regarding the psychological effects of thermal injury on children; Part 2 with aspects of the thermally injured group and Part 3 with psychological effects on their mothers. A total of 44 thermally injured (aged 11-16 years) injured 3-14 years previously, were matched according to age, sex, burn percentage and site of injury. In-depth interviewing and questionnaire responses on measures of psychological disturbance indicated that thermally injured children were differentiated in terms of psychopathology from matched Fracture Controls and Normal Controls. Such differences embraced many aspects of social and recreational functioning, and group differences emphasised depression, anxiety (particularly situational anxiety) and anti-social disorder as being particularly prominent in the thermally injured group. Therapeutic approaches are briefly discussed.

Background. The Malawi Liverpool Wellcome Trust Clinical Research Programme (MLW) has routinely collected specimens for blood culture from febrile patients, and cerebrospinal fluid from patients with suspected meningitis, presenting to Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi, since 1998. Methods. We present bloodstream infection (BSI) and meningitis surveillance data from 1998 to 2014. Automated blood culture, manual speciation, serotyping, and antimicrobial susceptibility testing were performed at MLW. Population data for minimum-incidence estimates in urban Blantyre were drawn from published estimates. Results. Between 1998 and 2014, 167 028 blood cultures were taken from adult and pediatric medical patients presenting to QECH; Salmonella Typhi was isolated on 2054 occasions (1.2%) and nontyphoidal Salmonella (NTS) serovars were isolated 10 139 times (6.1%), of which 8017 (79.1%) were Salmonella Typhimurium and 1608 (15.8%) were Salmonella Enteritidis. There were 392 cases of NTS meningitis and 9 cases of Salmonella Typhi meningitis. There have been 3 epidemics of Salmonella BSI in Blantyre; Salmonella Enteritidis from 1999 to 2002, Salmonella Typhimurium from 2002 to 2008, and Salmonella Typhi, which began in 2011 and was ongoing in 2014. Multidrug resistance has emerged in all 3 serovars and is seen in the overwhelming majority of isolates, while resistance to third-generation cephalosporins and fluoroquinolones is currently uncommon but has been identified. Conclusions. Invasive Salmonella disease in Malawi is dynamic and not clearly attributable to a single risk factor, although all 3 epidemics were associated with multidrug resistance. To inform nonvaccine and vaccine interventions, reservoirs of disease and modes of transmission require further investigation.

Introduction Nontyphoidal Salmonellae (NTS) are responsible for a huge burden of bloodstream infection in Sub-Saharan African children. Recent reports of a decline in invasive NTS (iNTS) disease from Kenya and The Gambia have emphasised an association with malaria control. Following a similar decline in iNTS disease in Malawi, we have used 9 years of continuous longitudinal data to model the interrelationships between iNTS disease, malaria, HIV and malnutrition. Methods Trends in monthly numbers of childhood iNTS disease presenting at Queen’s Hospital, Blantyre, Malawi from 2002 to 2010 were reviewed in the context of longitudinal monthly data describing malaria slide-positivity among paediatric febrile admissions, paediatric HIV prevalence, nutritional rehabilitation unit admissions and monthly rainfall over the same 9 years, using structural equation models (SEM). Results Analysis of 3,105 iNTS episodes identified from 49,093 blood cultures, showed an 11.8% annual decline in iNTS (p < 0.001). SEM analysis produced a stable model with good fit, revealing direct and statistically significant seasonal effects of malaria and malnutrition on the prevalence of iNTS disease. When these data were smoothed to eliminate seasonal cyclic changes, these associations remained strong and there were additional significant effects of HIV prevalence. Conclusions These data suggest that the overall decline in iNTS disease observed in Malawi is attributable to multiple public health interventions leading to reductions in malaria, HIV and acute malnutrition. Understanding the impacts of public health programmes on iNTS disease is essential to plan and evaluate interventions., Author Summary Invasive nontyphoidal Salmonella (iNTS) disease is estimated to be responsible for 680,000 deaths/year and yet this is widely under-recognised by clinicians, epidemiologists and policymakers in Sub-Saharan Africa. Recently there have been reports of a decline in childhood iNTS disease from both Kenya and The Gambia that have been attributed to malaria control, and this has led to the unsubstantiated assumption that NTS disease will disappear. While this may be true in certain settings, numerous studies have also associated HIV and malnutrition with NTS disease. We therefore re-assessed this multifaceted relationship in Malawi, where we have previously reported little change in malaria cases, but where there have been highly successful antiretroviral and malnutrition programmes. Analysis of ~50,000 blood cultures and ~240,000 malaria slides demonstrates a significant decline in iNTS attributable to malaria, HIV and malnutrition, emphasising the complex inter-relationships between these factors and suggest that malaria interventions alone are unlikely to control iNTS disease. Our findings are highly relevant to the neglected field of bacteraemia in Africa and understanding the direct and indirect impacts of public health programmes on iNTS disease in Africa is essential for policy makers to plan and evaluate interventions to control this condition.

It has been suggested that patients with strong religious beliefs or religious delusions have poor outcome from psychiatric treatment. The aim of the investigation was to establish if the patients’ shorter-term response to psychiatric treatment was affected by these factors. A quasi-experimental design was used, in which patients with schizophrenia were assessed soon after admission to hospital. They were categorised as (1) religious or not religious, (2) experiencing religious delusions or not, using reliable criteria. Patients were given their routine treatment and their symptoms were then re-assessed after four weeks. There was no difference in response to treatment between the religious and non-religious patients. There was no difference between patients who had religious delusions and those who had other types of delusions. Though this study does not settle the debate, it suggests that strong religious beliefs or religious delusions do not adversely affect the patient's response to treatment in the s...

A meta-analysis was conducted of correlations between job satisfaction and measures of health for samples originating from Hong Kong. Using established procedures and a priori selection criteria, 22 samples were combined from published and unpublished sources, in a combined sample of 4492 workers from various industries and occupations. Results indicated relationships between job satisfaction and health for Hong Kong employees were high, and notably different from the larger sample in the HERMES study (Cass, Faragher & Cooper2003). The moderator analysis revealed that samples comprising an approximately equal gender mix had larger correlations than samples of mostly women, or mostly men. Our comparison of studies with differential methodological rigour indicated that this had a minimal impact on combined effect size. Copyright © 2003 John Wiley & Sons, Ltd.

Measures of religiosity validated for psychotic patients do not exist. This study sought to examine the psychometric properties of a modified version of the Religious Life Inventory (RLI) in this population. It was anticipated that religiosity would be affected by psychotic symptoms. The religiosity of patients with schizophrenia was assessed while symptoms were more evident and again after treatment, to evaluate changes in religiosity. Four factors were found which characterized the religiosity of people with schizophrenia. These factors were found to have good construct validity. Patient's responses indicated a reduced need for religion when re-assessed once symptom scores were reduced.

The outcome of infection with hepatitis C virus (HCV) varies greatly. The virus associates with serum lipoproteins, including those containing apolipoprotein E (apoE) and apolipoprotein B (apoB), and may enter cells via the low-density lipoprotein receptor (LDLR). ApoE genotypes can affect the extent of damage in diseases caused by 2 other viruses--herpes simplex virus type 1 (HSV1; in Alzheimer's disease and herpes labialis) and human immunodeficiency virus (HIV). We therefore investigated whether specific apoE and apoB alleles were associated with different outcomes of HCV infection. A total of 156 anti-HCV-positive patients and 104 non-HCV-infected patients were studied. Liver biopsy specimens from patients with chronic HCV infection (n = 111) were assessed for disease severity by the Knodell system. ApoE and apoB genotypes were determined by standard polymerase chain reaction (PCR) methods. There was no significant difference among the apoE genotypes of HCV-infected subjects compared with previously published population data, or between HCV-RNA positive or negative patients. However, chronically HCV-infected subjects with mild liver disease (n = 65) had a significantly higher apoE-epsilon 4 allele frequency (20.0%) than those (n = 46) with severe disease (6.5%). ApoB alleles alone or in combination with apoE were not associated with mild or severe disease. The overall apoE allele frequencies of patients with liver disease not caused by HCV were similar to those of the total HCV group and in contrast to the HCV patients, the apoE allele frequencies were similar in those patients with no or mild fibrosis as compared with those with bridging fibrosis or cirrhosis. In conclusion, carriage of an apoE-epsilon 4 allele may be protective against liver damage caused by HCV, but not against damage due to various nonviral causes. This is yet another case in which apoE may determine the severity of a viral disease.

Free-radical activity in coronary venous outflow was assessed before and after reperfusion in nine patients with acute infarction who had undergone successful recanalization of the infarct-related artery by primary coronary angioplasty. Free-radical activity was measured in serum samples from coronary venous outflow over a timed period of 24 hours by using (1) the percentage molar ratio (PMR) of the diene conjugate 9,11-linoleic acid, and (2) malonaldehyde concentration. Preangioplasty PMR means lay within the normal range, but showed a marked increase soon after successful recanalization. Relative to baseline, the changes over time reached statistical significance between 2 and 60 minutes. No statistically significant changes in malonaldehyde occurred over the study period. We conclude that successful recanalization of the infarct artery is associated with significantly elevated free-radical activity, as measured by the PMR of conjugated diene, in coronary venous outflow. Such patients may be at risk from free radical mediated reperfusion injury.

Background In spite of the significant mortality associated with Plasmodium falciparum infection, the mechanisms underlying severe disease remain poorly understood. We have previously shown evidence of endothelial activation in Ghanaian children with malaria, indicated by elevated plasma levels of both von Willebrand factor (VWF) and its propeptide. In the current prospective study of children in Malawi with retinopathy confirmed cerebral malaria, we compared these markers with uncomplicated malaria, non malarial febrile illness and controls. Methods and Findings Children with cerebral malaria, mild malaria and controls without malaria were recruited into the study. All comatose patients were examined by direct and indirect ophthalmoscopy. Plasma VWF and propeptide levels were measured by ELISA. Median VWF and propeptide levels were significantly higher in patients with uncomplicated malaria than in children with non-malarial febrile illness of comparable severity, in whom levels were higher than in non-febrile controls. Median concentrations of both markers were higher in cerebral malaria than in uncomplicated malaria, and were similar in patients with and without retinopathy. Levels of both VWF and propeptide fell significantly 48 hours after commencing therapy and were normal one month later. Conclusions In children with malaria plasma VWF and propeptide levels are markedly elevated in both cerebral and mild paediatric malaria, with levels matching disease severity, and these normalize upon recovery. High levels of both markers also occur in retinopathy-negative ‘cerebral malaria’ cases, many of whom are thought to be suffering from diseases other than malaria, indicating that further studies of these markers will be required to determine their sensitivity and specificity.

BACKGROUND Free-radical generation after successful thrombolysis in acute myocardial infarction may jeopardize ischaemic but viable myocardium, thus limiting the optimal benefits of reperfusion. METHODS Circulating free-radical activity was assessed in 25 consecutive patients with acute myocardial infarction. Those who successfully reperfused (Group A) were compared with those who did not (Group B). We also compared patients who had or had not developed Q waves and patients with and without previous angina or myocardial infarction. All patients presented within 6 h of the onset of chest pain and received standard intravenous streptokinase therapy. Free-radical activity in serial serum samples collected over 72 h was measured using the percentage molar ratio (PMR) of the concentrations of 9,11-linoleic acid to 9,12-linoleic acid, and malonaldehyde concentration. RESULTS Throughout the study period Group A (n = 11) showed significantly greater change in serum PMR and malonaldehyde levels compared with Group B (n = 14) (P < 0.01). PMR differences between the two groups were most pronounced at 3 and 12 h (P < 0.001). Patients with non-Q-wave myocardial infarction (n = 5) showed significantly greater changes in serum PMR and malonaldehyde levels (P < 0.01) compared with those with Q-wave infarction (n = 20). A history of previous infarction or angina had no apparent effects on the changes in serum free-radical activity. CONCLUSIONS Successful early reperfusion and non-Q-wave myocardial infarction are both associated with a significantly greater increase in the levels of markers of serum free-radical activity immediately after infarction. The results support present concepts of free-radical-mediated reperfusion injury. Use of these assays may identify those patients who may be at risk from free-radical-mediated reperfusion injury.

SynopsisThis quasi-prospective study of 2163 women attending a breast-screening clinic for a routine medical check-up indicates that certain types of coping strategies and personality dispositions predispose some women to an increased risk of developing breast cancer following the occurrence of a major life-event such as bereavement or other loss-related event. Regular exposure to stress situations appears to reduce the risk of a malignancy; experiencing a single, major life event was found to be potentially much more damaging, particularly if the individual was unable to externalize her emotions and obtain appropriate help and counselling.

Background. Salmonellae are facultative intracellular pathogens. Non-typhoid salmonellae (NTS) cause selflimiting mucosal disease in immunocompetent adults but invasive, recurrent disease among human immunodeficiency virus (HIV)‐infected adults in Africa. The importance of intracellular NTS infection in HIV is unknown. Methods. We performed quantitative pour-plate culture of blood samples obtained during febrile events among 495 Malawian adults on 871 occasions, and NTS were isolated at 158 events. Ninety-eight percent were HIV infected, with a median CD4 count of 67 cells/mL. Lysis of pour plates and gentamicin exclusion testing were used to investigate the presence of intracellular NTS in blood and bone marrow. Results. Total viable NTS counts in blood were low (1 colony-forming unit [CFU]/mL) but correlated independently with lower CD4 count and with IL-10 and IL-6 levels, especially at recurrence, suggesting failure to clear intracellular infection. Viable NTS load in blood and bone marrow were closely correlated at index events, but NTS were significantly concentrated in bone marrow, compared with blood samples, at recurrences (6 vs 1 CFU/mL), suggesting systemic tissue replication. Both lysis-pour-plating and gentamicin exclusion testing demonstrated intracellular infection with 11 CFU/cell in both blood and bone marrow specimens. Intracellular bacteria were demonstrated in bone marrow at both index and recurrent events, showing that this is an early and enduring feature of pathogenesis, but intracellular NTS were detected in blood only at index events, particularly in patients with a CD4 count !50 cells/mL. Intravascular NTS at recurrence may therefore reflect extracellular “overspill” from an intracellular sanctuary site, following failure of immunological control. Conclusions. Invasive NTS have established a new and emerging pathogenesis in the context of HIV infection in Africa.

Age-associated changes in the structure and function of the neurohypophysis may contribute to the decreased ability to conserve water in older animals. We investigated the neurohypophyses of 6 and 28-month-old male mice using radioimmunoassay and quantitative morphological techniques. The dry-weight and volume of the neurohypophysis increased significantly with age but the quantity of vasopressin in the gland remained constant. Oxytocin levels decreased with age. A quantitative morphological analysis was performed on the compartments of the neurohypophysis from male mice of 6 and 28 months of age which were either normally hydrated, osmotically loaded, or osmotically loaded and rehydrated. The absolute volumes of the axon endings, swellings, their constituent organelles and the axon terminals containing degenerating subcellular components were determined. The design of the analysis allowed us to examine both age-related changes and statistical interactions between the age of the animal and the behaviour of a variable during the osmotic loading/rehydration phase of the experiment. There was a significant age-related reduction in the volume of the neurohypophysis occupied by the endings and swellings. The diameters of the neurosecretory granules found in the endings were significantly smaller than those in the swellings in both age groups but the size difference was greater in the young animals. Dehydration and subsequent rehydration of old male mice leads to extensive re-modelling of the neurohypophysial compartments and subcellular organelles to the configuration found in the adult animal.

Part 3 of this study focused on maternal psychopathology and relationship with their children in three groups, assessed in Parts 1 and 2. Evidence of greater psychopathology in the mothers of burned children was supported by findings of both interview and self-report data, which indicated more symptoms of worry, depression, tension, anxiety, lack of energy, lower self confidence with other people and guilt, compared with mothers of Fracture Clinic and Normal Controls. Marital and social functioning and adverse life events did not differentiate groups, with the exception of a significantly higher divorce rate in the parents of burned children, following thermal injury.

Background Religious delusions are clinically important because they may be associated with selfharm and poorer outcomes from treatment. They have not been extensively researched. This study sought to investigate the prevalence of religious delusions in a sample of patients admitted to hospital with schizophrenia, to describe these delusions and to compare the characteristics of the patients with religious delusions with schizophrenia patients with all other types of delusion. Method A cross-sectional investigation was carried out. The prevalence of religious delusions was assessed and comparisons were made between religiously deluded patients and a control group on demographic, symptom, functioning and religious variables. One hundred and ninety-three subjects were examined of whom 24% had religious delusions. Results Patients with religious delusions had higher symptom scores (as measured by the PANSS), they were functioning less well (as measured by the GAF) and they were prescribed more medication than those patients with schizophrenia who had other types of delusion. Conclusion It is concluded that religious delusions are commonly found in schizophrenia and that by comparison with other patients who have schizophrenia, those patients with religious delusions appear to be more severely ill. This warrants further investigation.

matic factors as strong predictors of mortality from cancer, ischaemic heart disease and stroke: The Yugoslav prospective study. Journal of Psychosomatic Research, 29, 167-176. Grossarth-Maticek, R., & Eysenck, H. J. (1990). Personality, stress and disease: Description and validation of a new inventory. Psychological Reports, 66, 355-373. Grossarth-Maticek, R., Eysenck, H. J., & Vetter, H. (1988). Personality type, smoking habit and their interaction as predictors of cancer and coronary heart disease. Personality and Individual Differences, 9, 479-495. Grossarth-Maticek, R., Eysenck, H. J., Vetter, H., & Schmidt, P. (1988). Psychological types and chronic diseases: Results of the Heidelberg prospective psychosomatic intervention study. In S. Maes, C. D. Spielberger, P. B. Defares, & J. G. Sarason (Eds.), Topics in health psychology (pp. 57-75). London: Wiley. Grossarth-Maticek, R., Kanazir, D. T., & Schmidt, P. (1982). Psychosomatic factors in the process of cancerogenesis. Psychotherapy and Psychosomatics, 38, 284-302. Grossarth-Maticek, R., Kanazir, D. T., Schmidt, P., & Vetter, H. (1985). Psychosocial and organic variables as predictors of lung cancer, cardiac infarct and apoplexy: Some differential predictors. Personality and Individual Dibfferences, 6, 313-321. Grossarth-Maticek, R., Kanazir, D. T., Vetter, H., & Schmidt, P. (1983). Psychosomatic factors involved in he process of cancerogenesis. Psychotherapy and Psychosomatics, 40, 191-210. Grossarth-Maticek, R., Siegrist, J., & Vetter, H. (1982). Interpersonal repression as a predictor of cancer. Social Science Medicine, 16, 493498. Holland, J. C. (1987). Update on emotions and cancer: Clinical implications and problems. In J. C. Holland, M. J. Massie, & L. M. Lesko (Eds.), Current concepts inpsycho-oncology andAIDS (pp. 3-9). New York: Memorial Sloan-Kettering Cancer Center. Temoshok, L., & Heller, B. W. (1984). On comparing apples, oranges and fruit salad: A methodological overview of medical outcome studies in psychosocial oncology. In L. L. Cooper (Ed.), Psychosocial stress and cancer (pp. 231-260). Chichester, England: Wiley. Vetter, H. (1990). Erste Uberprufung der Voraussagbarkeit von Todesfdllen in der Heidelberger Untersuchung 1972 von GrossarthMaticek, wenn bei Ablieferung der Pradiktorvariablen die einschldgige Erkrankung noch nicht bekannt gewesen zu sein scheint [First investigation of deaths' predictability in the 1972 GrossarthMaticek Heidelberg study, when during time of depositing the predictor-variables the pertinent disease did not seem to be known]. Unpublished manuscript. Ziegler, G. (1983). Psychosomatische Aspekte der Onkologie [Psychosomatic aspects in oncology]. Stuttgart: Enke.

SynopsisThis study explored the incidence and perception of psychosocial stress among 1596 patients attending breast screening clinics and 567 controls attending a well women clinic. It was found that some major life events (e.g. death of husband, death of close friend) were significantly related to breast disease and severity. The implications of the results are discussed.

Objectives In low-resource settings, limitations in diagnostic accuracy of chest X-rays (CXR) for pulmonary tuberculosis (PTB) relate partly to non-expert interpretation. We piloted a TB CXR Image Reference Set (TIRS) to improve non-expert performance in an operational setting in Malawi. Methods Nineteen doctors and clinical officers read 60 CXR of patients with suspected PTB, at baseline and using TIRS. Two officers also used the CXR Reading and Recording System (CRRS). Correct treatment decisions were assessed against a “gold standard” of mycobacterial culture and expert performance. Results TIRS significantly increased overall non-expert sensitivity from 67.6 (SD 14.9) to 75.5 (SD 11.1, P = 0.013), approaching expert values of 84.2 (SD 5.2). Among doctors, correct decisions increased from 60.7 % (SD 7.9) to 67.1 % (SD 8.0, P = 0.054). Clinical officers increased in sensitivity from 68.0 % (SD 15) to 77.4 % (SD 10.7, P = 0.056), but decreased in specificity from 55.0 % (SD 23.9) to 40.8 % (SD 10.4, P = 0.049). Two officers made correct treatment decisions with TIRS in 62.7 %. CRRS training increased this to 67.8 %. Conclusion Use of a CXR image reference set increased correct decisions by doctors to treat PTB. This tool may provide a low-cost intervention improving non-expert performance, translating into improved clinical care. Further evaluation is warranted. Key Points • Tuberculosis treatment decisions are influenced by CXR findings, despite improved laboratory diagnostics. • In low-resource settings, CXR interpretation is performed largely by non-experts. • We piloted the effect of a simple reference training set of CXRs. • Use of the reference set increased the number of correct treatment decisions. This effect was more marked for doctors than clinical officers. • Further evaluation of this simple training tool is warranted. Electronic supplementary material The online version of this article (doi:10.1007/s00330-013-2840-z) contains supplementary material, which is available to authorized users.

Background Missing outcomes can seriously impair the ability to make correct inferences from randomized controlled trials (RCTs). Complete case (CC) analysis is commonly used, but it reduces sample size and is perceived to lead to reduced statistical efficiency of estimates while increasing the potential for bias. As multiple imputation (MI) methods preserve sample size, they are generally viewed as the preferred analytical approach. We examined this assumption, comparing the performance of CC and MI methods to determine risk difference (RD) estimates in the presence of missing binary outcomes. We conducted simulation studies of 5000 simulated data sets with 50 imputations of RCTs with one primary follow-up endpoint at different underlying levels of RD (3–25 %) and missing outcomes (5–30 %). Results For missing at random (MAR) or missing completely at random (MCAR) outcomes, CC method estimates generally remained unbiased and achieved precision similar to or better than MI methods, and high statistical coverage. Missing not at random (MNAR) scenarios yielded invalid inferences with both methods. Effect size estimate bias was reduced in MI methods by always including group membership even if this was unrelated to missingness. Surprisingly, under MAR and MCAR conditions in the assessed scenarios, MI offered no statistical advantage over CC methods. Conclusions While MI must inherently accompany CC methods for intention-to-treat analyses, these findings endorse CC methods for per protocol risk difference analyses in these conditions. These findings provide an argument for the use of the CC approach to always complement MI analyses, with the usual caveat that the validity of the mechanism for missingness be thoroughly discussed. More importantly, researchers should strive to collect as much data as possible.

Oxygen-derived free radicals (FR) have been found to be important mediators of myocardial reperfusion injury in animal studies. In man, most studies of FR measurement after reperfusion have relied on indirect markers alone. However, their accuracy and relationship to FR's has been controversial. We have therefore used primary PTCA for AMI as a model of acute reperfusion to compare direct FR measurement using electron paramagnetic resonance (EPR) spectroscopy and the spin trap agent α-phenyl N-tert butyl nitrone, with two of the most commonly used indirect markers. These were: [1] the percentage molar ratio (PMR) of the diene conjugate 9,11-octa-decadieneoic acid to the naturally-occurring isomer 9,12-linoleic acid, and [2] serum malonaldehyde (MDA). 16 patients (mean age: 56.9 yrs, range 47–66). undergoing successful primary PTCA (8 LAD, 1 Intermed, 1 LCx, 6 RCA) of less than 6 h duration (mean 3.55 h, range 2.25–5.0). had venous sampling from the base of the right atrium/coronary sinus before angioplasty (TIMI 0) and at timed intervals up to 24 h after recanalisation (TIMI 3). Direct FR measurement using EPR showed a biphasic time-course. Relative to the pre-PTCA level, FR's increased sharply after 15 min (P l 0.05) with peak levels at 1½ and 3½ h (P l 0.001). Following a decline to 6 h a late peak was observed at 24 h which may originate from accumulating my ocardial leukocyte infiltration. Indirect FR measurement using PMR showed a significant increase between 15 min and 1½ h (P l 0.01) only. MDA levels remained unchanged throughout the study. These results demonstrate that compared to direct FR measurement using EPR, indirect markers used in this study have limited or no usefulness in assessing FR generation in AMI. Myocardial reperfusion studies in man should ideally use direct methods.