Clinico-Pathological discrepancies in the Diagnosis of Causes of Maternal Death in Sub-Saharan Africa: Retrospective Analysis

Background Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death. Methods and Findings A retrospective analysis of clinico-pathologic correlation was carried out, using necropsy as the gold standard for diagnosis. All maternal autopsies (n ¼ 139) during the period from October 2002 to December 2004 at the Maputo Central Hospital, Mozambique were included and major diagnostic discrepancies were analyzed (i.e., those involving the cause of death). Major diagnostic errors were detected in 56 (40.3%) maternal deaths. A high rate of false negative diagnoses was observed for infectious diseases, which showed sensitivities under 50%: HIV/AIDS-related conditions (33.3%), pyogenic bronchopneumonia (35.3%), pyogenic meningitis (40.0%), and puerperal septicemia (50.0%). Eclampsia, was the main source of false positive diagnoses, showing a low predictive positive value (42.9%). Conclusions Clinico-pathological discrepancies may have a significant impact on maternal mortality in sub-Saharan Africa and question the validity of reports based on clinical data or verbal autopsies. Increasing clinical awareness of the impact of obstetric and nonobstetric infections with their inclusion in the differential diagnosis, together with a thorough evaluation of cases clinically thought to be eclampsia, could have a significant impact on the reduction of maternal mortality.

Clinico-Pathological discrepancies in the Diagnosis of Causes of Maternal Death in Sub-Saharan Africa: Retrospective Analysis

Background Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death. Methods and Findings A retrospective analysis of clinico-pathologic correlation was carried out, using necropsy as the gold standard for diagnosis. All maternal autopsies (n ¼ 139) during the period from October 2002 to December 2004 at the Maputo Central Hospital, Mozambique were included and major diagnostic discrepancies were analyzed (i.e., those involving the cause of death). Major diagnostic errors were detected in 56 (40.3%) maternal deaths. A high rate of false negative diagnoses was observed for infectious diseases, which showed sensitivities under 50%: HIV/AIDS-related conditions (33.3%), pyogenic bronchopneumonia (35.3%), pyogenic meningitis (40.0%), and puerperal septicemia (50.0%). Eclampsia, was the main source of false positive diagnoses, showing a low predictive positive value (42.9%). Conclusions Clinico-pathological discrepancies may have a significant impact on maternal mortality in sub-Saharan Africa and question the validity of reports based on clinical data or verbal autopsies. Increasing clinical awareness of the impact of obstetric and nonobstetric infections with their inclusion in the differential diagnosis, together with a thorough evaluation of cases clinically thought to be eclampsia, could have a significant impact on the reduction of maternal mortality.

Health care utilization among immigrants and native-born populations in 11 European countries. Results from the Survey of Health, Ageing and Retirement in Europe

Objective: This study examines health care utilization of immigrants relative to the native-born populations aged 50 years and older in eleven European countries. Methods. We analyzed data from the Survey of Health Aging and Retirement in Europe (SHARE) from 2004 for a sample of 27,444 individuals in 11 European countries. Negative Binomial regression was conducted to examine the difference in number of doctor visits, visits to General Practitioners (GPs), and hospital stays between immigrants and the native-born individuals. Results: We find evidence those immigrants above age 50 use health services on average more than the native-born populations with the same characteristics. Our models show immigrants have between 6% and 27% more expected visits to the doctor, GP or hospital stays when compared to native-born populations in a number of European countries. Discussion: Elderly immigrant populations might be using health services more intensively due to cultural reasons.

Inter-rater agreement and reliability of the COSMIN (COnsensus-based Standards for the selection of health status Measurement Instruments) Checklist

Background: The COSMIN checklist is a tool for evaluating the methodological quality of studies on measurement properties of health-related patient-reported outcomes. The aim of this study is to determine the inter-rater agreement and reliability of each item score of the COSMIN checklist (n = 114). Methods: 75 articles evaluating measurement properties were randomly selected from the bibliographic database compiled by the Patient-Reported Outcome Measurement Group, Oxford, UK. Raters were asked to assess the methodological quality of three articles, using the COSMIN checklist. In a one-way design, percentage agreement and intraclass kappa coefficients or quadratic-weighted kappa coefficients were calculated for each item. Results: 88 raters participated. Of the 75 selected articles, 26 articles were rated by four to six participants, and 49 by two or three participants. Overall, percentage agreement was appropriate (68% was above 80% agreement), and the kappa coefficients for the COSMIN items were low (61% was below 0.40, 6% was above 0.75). Reasons for low inter-rater agreement were need for subjective judgement, and accustom to different standards, terminology and definitions.Conclusions: Results indicated that raters often choose the same response option, but that it is difficult on item level to distinguish between articles. When using the COSMIN checklist in a systematic review, we recommend getting some training and experience, completing it by two independent raters, and reaching consensus on one final rating. Instructions for using the checklist are improved.

Protocol of the COSMIN study: consensus-based standards for the selection of health measurement instruments

Background: Choosing an adequate measurement instrument depends on the proposed use of the instrument, the concept to be measured, the measurement properties (e.g. internal consistency, reproducibility, content and construct validity, responsiveness, and interpretability), the requirements, the burden for subjects, and costs of the available instruments. As far as measurement properties are concerned, there are no sufficiently specific standards for the evaluation of measurement properties of instruments to measure health status, and also no explicit criteria for what constitutes good measurement properties. In this paper we describe the protocol for the COSMIN study, the objective of which is to develop a checklist that contains COnsensus-based Standards for the selection of health Measurement INstruments, including explicit criteria for satisfying these standards. We will focus on evaluative health related patient-reported outcomes (HR-PROs), i.e. patient-reported health measurement instruments used in a longitudinal design as an outcome measure, excluding health care related PROs, such as satisfaction with care or adherence. The COSMIN standards will be made available in the form of an easily applicable checklist.Method: An international Delphi study will be performed to reach consensus on which and how measurement properties should be assessed, and on criteria for good measurement properties. Two sources of input will be used for the Delphi study: (1) a systematic review of properties, standards and criteria of measurement properties found in systematic reviews of measurement instruments, and (2) an additional literature search of methodological articles presenting a comprehensive checklist of standards and criteria. The Delphi study will consist of four (written) Delphi rounds, with approximately 30 expert panel members with different backgrounds in clinical medicine, biostatistics, psychology, and epidemiology. The final checklist will subsequently be field-tested by assessing the inter-rater reproducibility of the checklist.Discussion: Since the study will mainly be anonymous, problems that are commonly encountered in face-to-face group meetings, such as the dominance of certain persons in the communication process, will be avoided. By performing a Delphi study and involving many experts, the likelihood that the checklist will have sufficient credibility to be accepted and implemented will increase.

The significance of distributive effects in social assessment of health care

In this paper we address the importance of distributive effects in the social valuation of QALY's. We propose a social welfarefunction that generalises the functions traditionally used in the health economic literature. The novelty is that, depending on the individual health gains, our function can representeither preferences for concentrating or preferences for spreading total gain or both together, an issue which has notbeen addressed until now. Based on an experiment, we observe that this generalisation provides a suitable approximation tothe sampled social preferences.

Diversity and regional inequalities: Assessing the outcomes of the Spanish 'System of Health Care Services'

The consolidation of a universal health system coupled with a process of regionaldevolution characterise the institutional reforms of the National Health System(NHS) in Spain in the last two decades. However, scarce empirical evidence hasbeen reported on the effects of both changes in health inputs, outputs andoutcomes, both at the country and at the regional level. This paper examinesthe empirical evidence on regional diversity, efficiency and inequality ofthese changes in the Spanish NHS using cross-correlation, panel data andexpenditure decomposition analysis. Results suggest that besides significantheterogeneity, once we take into account region-specific needs there is evidenceof efficiency improvements whilst inequalities in inputs and outcomes, althoughmore visible , do not appear to have increased in the last decade. Therefore,the devolution process in the Spanish Health System offers an interesting casefor the experimentation of health reforms related to regional diversity butcompatible with the nature of a public NHS, with no sizeable regionalinequalitiest.

Testing the descriptive performance of the rank-dependent utility in the domain of health profiles

Expected utility theory (EUT) has been challenged as a descriptive theoryin many contexts. The medical decision analysis context is not an exception.Several researchers have suggested that rank dependent utility theory (RDUT)may accurately describe how people evaluate alternative medical treatments.Recent research in this domain has addressed a relevant feature of RDU models-probability weighting-but to date no direct test of this theoryhas been made. This paper provides a test of the main axiomatic differencebetween EUT and RDUT when health profiles are used as outcomes of riskytreatments. Overall, EU best described the data. However, evidence on theediting and cancellation operation hypothesized in Prospect Theory andCumulative Prospect Theory was apparent in our study. we found that RDUoutperformed EU in the presentation of the risky treatment pairs in whichthe common outcome was not obvious. The influence of framing effects onthe performance of RDU and their importance as a topic for future researchis discussed.

The social value of health programs: Is age a relevant factor?

In cost-effectiveness analysis (CEA) it is usually assumed that a QALY is of equal value to everybody, irrespective of the patient's age. However, it is possible that society assigns different social values to a QALY according to who gets it. In this paper we discuss the possibility of weighting health benefits for age in CEA. We also examinethe possibility that age-related preferences depend on the size of the health gain. An experiment was performedto test these hypotheses. The results assessing suggest that the patient's age is a relevant factor when assessing health gains.

Comparison and evaluation of states of health

Starting from a finite or countable set of states of health, and assumingthe existence of an objective transitive preference relation on that set,we propose a way of performing interpersonal comparisons of states ofhealth. In so doing, we first consider the population divided into types,and consider that two individuals of a different type have a comparablestate of health whenever they sit at the same centile of their respectivetype. A way of comparing and evaluating states of health for differentgroups is then proposed and rationalized. This can be viewed as both analternative and an extension of the traditional QALY approach.

Array-CGH in patients with a clinical diagnosis of Kabuki syndrome: identification of two cases with terminal 2q37 deletion and no other recurrent rearrangement

Background: Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown. Methods: We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited. Results: No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group. Conclusion: Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered.

Synovial fluid examination for the diagnosis of synovial amyloidosis in patients with chronic renal failure undergoing haemodialysis

The diagnosis of synovial amyloidosis is based upon synovial biopsy. Synovial fluid (SF) in seven patients with amyloid arthropathy associated with chronic renal failure undergoing haemodialysis were studied. The SF and synovial samples of 10 consecutive patients with seronegative mono- or oligoarthritis served as controls. Six of the seven patients with amyloid positive synovial biopsy specimens showed amyloid in their SF. No amyloid was found in the synovial tissue or fluid of the 10 patients in the control group, the sensitivity being 87.7%. The finding of amyloid in SF was highly reproducible, showing its presence in the same joint on several occasions. The deposits were Congophilia resistant to potassium permanganate pretreatment, and the immunohistochemical analysis proved that they contained beta 2 microglobulin. The high sensitivity and good reproducibility of the method shows that the finding of amyloid in SF is sufficient for the diagnosis of synovial amyloidosis. It is possible to perform immunohis

Role of technetium-99m diphosphonate and gallium-67 citrate bone scanning in the early diagnosis of infectious spondylodiscitis: a comparative study

A comparative study of the parts played by technetium-99m diphosphonate and gallium-67 citrate bone scanning in the early diagnosis of infectious spondylodiscitis is presented. Nineteen patients were included in the study. All patients (11 men aged 19-70 years and eight women aged 18-72 years) had a history of back pain varying in duration from one to 15 weeks. A 99mTc diphosphonate bone scan was positive in 17 patients. The two patients with negative results had less than two weeks of back pain. The 67Ga citrate bone scan showed uptake in all patients.

A comparison of the accuracy of peritoneoscopy and liver biopsy in the diagnosis of cirrhosis

The accuracy of peritoneoscopy and liver biopsy in the diagnosis of hepatic cirrhosis was compared in 473 consecutive patients submitted to both procedures. One hundred and fifty-two of them had cirrhosis diagnosed by one or both methods. There was 73% agreement between the two procedures. `Apparent' false-negative results were 17·7% for peritoneoscopy and 9·3% for liver biopsy. The incidence of false-negative results in the diagnosis of cirrhosis can be reduced by combining both procedures.