[Problems of case definition and case finding (author's transl)].
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Epidemiologic Methods↗
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Epidemiological survey of definite cases of Meniere's disease collected by the seventeen members of the Meniere's Disease Research Committee of Japan in 1975--1976.
Between Aril 1975 and December 1976, the second nationwide survey of Meniere's disease in Japan was made by the 17 members of the Meniere's Disease Research Committee of Japan. The epidemiological data from 520 patients with definite Meniere's disease were analyzed in comparison with those from the 126 patients in the non-Meniere vertiginous group (Control A) and the 228 patients in the rhinolaryngological group (Control B). The male:female ratio of definite cases of Meniere's disease was almost the same, and the age distribution peaked at the age group of 40--49 years for males, while the peak for females was at the age group of 30--39 years. 5.8% of the 520 patients had a close relative who also suffered from Meniere's disease. From the epidemiological features, it may appear that the occurrence of vertiginous attacks in Meniere's disease is influenced much more by individual than by environmental factors. However, this feature can be considered as another evidence of the psychosomatic disorders involved in Meniere's disease.
Age Factors↗
Diagnostic and phylogenetic perspectives of the 2023 Murray Valley encephalitis virus outbreak in Australia: an observational study.
BACKGROUND: An outbreak of Murray Valley encephalitis virus (MVEV), the largest since 1974, was observed in Australia between Jan 1 and July 31, 2023. This study aims to characterise the utility of diagnostic platforms, testing algorithms, and genomic characteristics of MVEV to facilitate a comprehensive framework for MVEV testing and surveillance in the outbreak setting. METHODS: In this observational study, we assessed flavivirus diagnostics for all patients with suspected Murray Valley encephalitis in Australia from Jan 1 to July 31, 2023. We included all patients with confirmed Murray Valley encephalitis, probable Murray Valley encephalitis, or acute unspecified flavivirus infection using the Communicable Diseases Network Australia case definition. Cases were excluded if an alternative diagnosis was identified. We collected blood, serum, cerebrospinal fluid, brain tissue, urine, or a combination of these samples, as appropriate and at the discretion of the treating clinician. We conducted multimodal diagnostic testing, which included flavivirus-specific serological and nucleic acid amplification testing. Metagenomic next-generation sequencing, including next-generation deep sequencing, target-enrichment, and targeted amplification, was conducted on human and representative mosquito-derived samples obtained from established mosquito population surveillance programmes for phylogenetic analysis. FINDINGS: 27 patients with encephalitis were assessed for MVEV between Jan 1, 2023, and July 31, 2023, 23 (85%) of whom fulfilled national case definitions for confirmed Murray Valley encephalitis. Patient ages ranged from 6 weeks to 83 years (median 62·0 years [IQR 31·0-67·5]) and patients were mostly male (21 [78%] male patients and six [22%] female patients). Incidence varied widely by geographical region and was highest in the Northern Territory (32·0 per 1 000 000 population). Diagnostic specimen collection generally occurred promptly (median 6·0 days [IQR 4·0-14·5] from symptom onset to diagnostic specimen collection). In seven patients, case assignation relied on convalescent serum samples to assess for seroconversion or an appropriate rise in antibody titre (to four times the initial value or greater), or both. MVEV-specific IgM was detectable in serum samples of 17 (81%) of 21 patients tested by day 7 and MVEV IgG or total antibody (TAb) were detected in 18 (100%) of 18 patients tested by day 30. MVEV-specific IgM (or TAb) and MVEV RNA were detected in cerebrospinal fluid collected within 14 days of symptom onset in nine (39%) of 23 patients and seven (28%) of 25 patients, respectively. Phylogenetic analysis revealed two circulating MVEV genotypes, G1A and G2, in mosquitoes and humans in 2023. In southeast Australia, only G1A was detected and probably introduced from enzootic foci in northern Australia. INTERPRETATION: This study provides a comprehensive overview of the diagnostic workflows and phylogenetic evaluations used during the 2023 MVEV outbreak in Australia, emphasising the importance of a multimodal approach for accurate and timely confirmation of flavivirus infection. Further One Health surveillance for MVEV and other zoonotic flaviviruses is key, given potential expanded ecological niches in the context of episodic climatic events. FUNDING: None.
Humans↗
Frequency of systemic lupus erythematosus in different ethnic groups in Hawaii.
A survey of systemic lupus erythematosus (SLE) patients was conducted in civilian general hospitals on Oahu, Hawaii for the years 1970-75. One hundred sixty-eight cases were ascertained, of which 107 were considered "definite." Age-adjusted prevalence rates per 100,000 were estimated for definite cases at the end of 1975 as follows: white 5.8, Chinese 24.1, Filipino 19.9, part-Hawaiian 20.4, and Japanese 18.2. There was a heavy preponderance of females in each ethnic group, averaging 90% of the definite cases overall. Review of vital statistics for the United States and Hawaii during this period showed age-adjusted SLE mortality rates per million as follows: U.S. white 3.04, U.S. non-white 8.82, Hawaii white 1.89, Hawaii non-white 14.46. The cause of the very high SLE prevalence and mortality in the Oriental and Polynesian people of Hawaii is not clear.
Adolescent↗
Visual and somatosensory evoked cortical potentials in multiple sclerosis.
The diagnostic value of the pattern reversal evoked cortical potential (VEP) and the somatosensory evoked cortical potential (SEP) has been compared in 50 patients with established or suspected multiple sclerosis. A prolonged latency of VEP was found in 96% of definite cases of multiple sclerosis, 58% of probable cases, and 20% of possible cases. A prolonged latency of SEP by stimulation of median or peroneal nerves or both was found in 86% of definite cases of multiple sclerosis, 83% of probable cases, and 50% of possibe cases. When combining the results of all three tests the diagnostic yield increased to 100%, 92%, and 50%, respectively.
Adult↗
A narrative systematic review of definitions and diagnostic criteria for disordered eating and eating disorders in type 1 diabetes.
AIMS/HYPOTHESIS: Type 1 diabetes and disordered eating (T1DE) affects 8-37.1% of adults and is associated with high rates of morbidity and mortality. The absence of a standardised case definition of T1DE and its severity hinders effective screening, diagnosis and treatment. This systematic review aimed to (1) synthesise existing case definitions and diagnostic criteria for T1DE in adults and (2) identify key characteristics to inform consensus for future diagnostic criteria. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Eligible studies involved adults (≥18 years) with type 1 diabetes assessing disordered eating; paediatric studies, mixed samples without disaggregated data, non-empirical designs and non-English publications were excluded. PubMed, MEDLINE, EMBASE, CINAHL and PsycINFO were searched up to November 2025 for peer-reviewed studies involving adults with T1DE. Qualitative and quantitative data on definitions, diagnostic criteria and assessment tools were extracted. Study quality was appraised using a modified Graphical Appraisal Tool for Epidemiological studies (GATE) checklist. Due to heterogeneity of data, a narrative synthesis of findings was performed to describe current definitions of T1DE. RESULTS: Sixty-one studies met the inclusion criteria, with a pooled sample of 111,208 participants (76% women) from over 22 countries. T1DE was defined using a heterogeneous array of terms, diagnostic frameworks and assessment tools (29 distinct methods). The Diabetes Eating Problem Survey-Revised (DEPS-R) was the most used questionnaire, but many studies relied on criteria adapted from general eating disorder classifications or generic questionnaires. Approximately three-quarters of the studies assessed insulin omission behaviours, but the operationalisation of the cognitions for insulin omission varied widely. Beyond physiological markers such as HbA1c and BMI, studies explored various diabetes-related and psychological constructs, although often considering diabetes and disordered eating separately rather than as an integrated condition. CONCLUSIONS/INTERPRETATION: This systematic review highlights the lack of a unified, evidence-based definition of T1DE, resulting in inconsistent screening, diagnostic and reporting practices. Establishing clear, consistent, evidence-based diagnostic criteria and screening questionnaires for T1DE is critical to improving early detection and developing targeted interventions. These findings provide a foundation for refining T1DE definitions as a stepping stone to an international consensus definition. STUDY REGISTRATION: PROSPERO registration no. CRD420250223622 FUNDING: King's College London and King's College Hospital through the KMRT KCH Joint Research Committee studentship. This work was also conducted as part of the National Institute for Health Research (NIHR; CS-2017-17-023)-funded STEADY project (Safe management of people with Type 1 diabetes and EAting Disorders studY). NZ's salary was part-funded by the NIHR via the NIHR Clinician Scientist award to MS; JT and KI are part-funded by the NIHR Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. MS was funded through her NIHR Clinician Scientist Fellowship (CS-2017-17-023).
Humans↗
Surgical injury of the common bile duct.
Review of our experience with twenty-two bile duct injuries and the literature leads us to the following conclusions: (1) Most biliary strictures follow surgery and can be avoided by adequate exposure, accurate dissection, use of hemostatic clips rather than clamps and ties, and the liberal use of operative cholangiography. (2) Injuries diagnosed at the time of surgery should be repaired by end-to-end anastomosis over a T tube if length is adequate or by Roux-en-Y choledochojejunostomy if length is inadequate. (3) The diagnosis of biliary injury should be suspected when jaundice, biliary fistula, or cholangitis occur in the postoperative period. (4) IVC, PTC, ERCP, or fistulography should be used when possible to delineate the site of injury or stricture and assist in planning the operative repair. (5) Surgery should be performed as soon as the diagnosis is made and the patient is in satisfactory condition for operation. (6) Early reoperation may be necessary to establish drainage and prepare for a later definitive procedure. In some cases, definitive repair can be performed this time. (7) Most late strictures should be repaired with a choledochojejunostomy to a defunctionalized limb of jejunum when resection and primary end-to-end repair cannot be accomplished.
Adult↗
[Surgical treatment of acute hemorrhagic pancreatitis. Report of 75 cases. (author's transl)].
Out of 75 definite cases of acute hemorrhagic pancreatitis, 39 were associated with a biliary lesion of which 16 were definitively the cause of the pancreatitis (11 embedded gall stones = 1/5th of the gall stones embedded in the ampulla of Vater and producing acute hemorrhagic pancreatitis). The biliary pancreatites were twice as severe as the primary pancreatites. This justifies the emergency exploration of the bile duct in any case of severe pancreatitis, suggesting acute hemorrhagic pancreatitis. The course of the disease is unforeseeable, certain large hematomas may become reabsorbed without sequelae. Thus one should be very circumspect concerning evaluation of the lesions during the first two weeks. This is why we reject any removal of pancreatic tissue during the first two or three weeks. We noted 30 deaths out of 70 cases of acute hemorrhagic pancreatitis during the postoperative period, 19 occurred during the first week. Concerning the 11 other deaths, they were in 9 cases very severe cases of acute hemorrhagic pancreatitis. Out of 41 cures, only 11 required secondary sequestrectomy, the 30 others were obtained without reoperation, often in spite of a large hematoma and clinical signs of severity. Our present attitude includes emergency operation of any severe case of pancreatitis in order to seek a biliary lesion with cholecystectomy (certain non-palpable calculi were thus discovered), radiomanometry of the common bile duct and, if necessary, sphincterotomy. The second operation is not always necessary, it should be carried out as late as possible after the 3rd week, sequestrectomy which is generally easy, may be carried out electively and under greater conditions of safety than necrosectomy or pancreatectomy.
Acute Disease↗
An estimate of the course of herpes simplex virus encephalitis.
Serologic responses, physical findings, and survival were studied in 51 cases of proved (14 patients) or presumptive (37 patients) herpes simplex encephalitis occurring in North America between 1965 and 1972. On the basis of a statistical analysis of 16 serological parameters tested in both groups, presumptive cases are likely similar to definitive cases. Using this assumption, the following tentatives conclusions are possible. Complement-fixing antibodies may be more sensitive measures of rises in anti-herpes simplex virus antibodies than are conventional or complement-requiring neutralizing or passive hemagglutinating antibodies. Mortality in herpes simplex virus encephalitis may vary from 0 to 80% and may be predictable depending upon the occurrence of seizures, paralysis and coma. Coma seems to dictate the dour prognosis. When 51 cases of herpes simplex virus encephalitis reported in the literature by others between 1944 and 1972 were analyzed by this method, a comparably varied mortality was obtained. It did not appear that treatment with idoxuridine increased the likelihood of survival.
Antibodies, Viral↗
Clozapine-induced agranulocytosis. A genetic and epidemiologic study.
An epidemic of agranulocytosis and granulocytopenia occurred in 1975 in conjunction with clozapine treatment of mental patients in Finland. An attempt was made to assess the epidemiologic and genetic factors contributing to the adverse drug effect. The estimated incidence rate in Finland was 2.1/1000 patient-months. This figure could not be compared with rates from other countries because of the inexact nature of the figures reported so far. All 16 cases occurred in seven hospitals in southwestern Finland, whereas the overall hospital net use of the drug was geographically evenly distributed. The difference between the observed and the proportionally expected incidence of cases amongst the hospitals where clozapine was used was statistically significant. The average consumption of the drug did not differ between the hospitals where cases occurred and those where no definite cases could be diagnosed. Six-generation pedigree analyses failed to reveal significant parental consanguinity or genetic kinship between probands. Neither did the birth places of the ancestors of the probands disclose a typical isolate pattern. In conclusion, the cases appeared to be confined to a few hospitals in southwestern Finland. Although a genetic factor is not excluded, we found no evidence in support of a genetic mechanism.
Agranulocytosis↗
Questionnaire survey of reported early congenital syphilis: problems in diagnosis, prevention, and treatment.
A retrospective questionnaire survey of a sample of 173 of the 360 cases of early congenital syphilis reported in 1972 revealed serious problems with diagnostic certainty, prevention, and treatment of congenital syphilis. Only 24 (13.9%) of the reported cases could be categorized as probably or definite cases based on criteria developed from a literature review. Forty percent of the mothers received no prenatal care and an additional 19% received no prenatal care until the third trimester. Initial and followup serologic testing was inadequate in those who received care. Eighty-three different penicillin treatment schedules were used in the treatment of 128 infants. Carefully reasoned diagnostic and therapeutic decision making about the management of congenital syphilis appears to be lacking.
Adolescent↗
Methods for defining equity-stratifying variables: a systematic review of validation studies.
BACKGROUND AND OBJECTIVE: Disease burden is often disproportionally higher among those who are socially disadvantaged by factors defined in the PROGRESS-Plus framework (ie, Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status, and Social capital, with "Plus" covering features like age and disability). The accuracy and applicability of case definitions to identify these variables from administrative and clinical health data are unknown. We conducted a systematic review to explore how equity-stratifying variables, as categorized by the PROGRESS-Plus framework, have been defined and validated in epidemiologic studies using administrative health, population-level, or electronic health record (EHR) data. METHODS: Medline, EMBASE, CINAHL, Web of Science, and Google Scholar were searched from the inception of the databases to 2024 for validation studies of equity-stratifying variables in adults using administrative health datasets, health registries, or EHR data. Titles and abstracts, followed by relevant full-text articles, were screened in duplicate by two reviewers for eligibility. The data sources utilized, algorithms employed, and their associated performance measures were extracted and synthesized from included studies. Given substantial heterogeneity in study design, equity-stratifying variable definition, and performance metrics, meta-analysis was not possible. RESULTS: Of the 9099 unique citations screened, 188 full texts were reviewed and 116 were included in this review. Most studies were published between 2019 and 2024 (n = 64, 55%) and were validation studies of race/ethnicity definitions that used race/ethnicity codes or surname list algorithms (n = 66, 57%). No studies examined religion. Regarding the reported performance measure estimates, the race/ethnicity/culture/language equity-stratifying variables category had the largest variability across sensitivity, positive predictive value (PPV), and Cohen's Kappa. Occupation validation studies had the lowest variation in sensitivity and PPV. CONCLUSION: Despite an increasing number of publications reporting on the validation of equity-stratifying variables relevant to the PROGRESS-Plus framework, performance measures varied widely across studies. The significant heterogeneity in equity-stratifying variable definitions and methods used to validate them support the need for further rigorous validation of equity-stratifying variables in administrative and clinical health data. PLAIN LANGUAGE SUMMARY: Disease burden is often higher in people who experience financial hardships, lower level of education, discrimination due to race/ethnicity, and unstable housing. These social factors can be considered health equity factors and are important for understanding health inequalities. Health researchers often use large datasets, such as hospital or electronic health records (EHRs), to study these health equity factors. However, it is not clear how accurately these data sources capture information about people's social circumstances and how these factors are defined. In this study, we reviewed existing research to understand how health equity factors have been defined across health data sources and how accurate they are at measuring aspects of health equity and social disadvantage. Of the more than 9000 studies we identified, we included 116 that met our criteria for this systematic review. Most included studies focused on identifying race and ethnicity, often using codes or surname-based methods. We found that the accuracy of these methods varied widely across studies, meaning results may not always be reliable or comparable. Overall, our findings show that there are inconsistencies in how social factors are defined and measured in health data. This makes it difficult to fully understand and address health inequalities using routinely collected health data. More work is needed to develop and validate better quality and more consistent methods for capturing these important social factors.
Humans↗
Teeside coronary survey--fatality and comparative severity of patients treated at home, in the hospital ward, and in the coronary care unit after myocardial infarction.
An epidemiological survey of myocardial infarction in Teesside County Borough was completed between April 1972 and April 1973. Cases were notified and divided into those who had suffered a 'definite', 'possible', or 'not' myocardial infarction. Severity factors were measured in the 'definite' cases and the distribution of the various factors studied among home, ward, and coronary care unit treated cases. Increasing severity was found to be related to increased fatality. The fatality of patients treated at home was less than that of those treated in the ward or the coronary care unit. Those who survived to be treated at home were not less severe than those who survived in a comparable group to be treated in hospital using the objective criteria described in the assessment of severity. It is emphasised that the results must be interpreted with caution as other essentially subjective criteria not so easily measurable, but which might have been of considerable influence in the assessment of severity, were not measured in this study.
Age Factors↗
Septicemia caused by Pseudomonas paucimobilis.
A case of septicemia caused by Pseudomonas paucimobilis is reported. This represents the first definitive case of disease produced by this yellow-pigmented, nonfermentative bacillus.
Aged↗
[Handskeleton studies with mammography technique in patients under antiepileptic medication (author's transl)].
An investigation with 114 epileptic patients under continuous treatment with anticonvulsiva was conducted in order to determine to what extent studies of the handskeleton with low-KV-technique will contribute to diagnosing osteopathy. The roentgenological findings of the hand were correlated with the x-ray findings of the remainder of the skeleton and with the results of biochemical studies. A control biopsy was performed in 8 cases. Definite and with all methods recognizable signs of osteomalacia were present in 7% of the cases, although only 2 patients developed a pathologic fracture. Another 32 patients (28%) showed suspicious changes in the handskeleton, which could not be confirmed by the comparative studies. No patient with normal findings of the handskeleton showed suspicious changes in the remainder of the skeleton or clinical and chemical indications of osteomalacia.
Adolescent↗
Complications associated with arteriovenous fistulas in patients undergoing chronic hemodialysis.
Over a two-year period, 100 venous angiograms were performed on 75 patients because of difficulty with vascular access. Seventy percent of the patients had decreased arterial flow or increased venous resistance. High output failure, sepsis, and aneurysm formation were also found. Venous angiography of the fistula demonstrated significant stenosis in 40% of the cases as well as total occlusion by thrombus in 9%, aneurysm formation in 7%, and abnormal fistula needle placement or anatomic abnormalities in 20% of the cases. Definitive diagnosis with the aid of venous angiography permitted specific surgical intervention in 62% of the cases, and identified new sites for needle placement in 18% of the cases, thus prolonging fistula life and reducing the need for new fistula placement. Our experience with local cellulitis of the fistula site and sepsis is also discussed.
Adult↗
Genome-wide association study of asthma with high treatment burden and/or worse outcomes defined using electronic healthcare data in UK Biobank.
BACKGROUND: In ∼10% of asthma patients, symptoms remain uncontrolled despite maximal treatment, representing an unmet clinical need. The causal variants, genes and pathways underlying genetic risk factors have not been fully elucidated, and it is unclear whether there are unique genetic risk factors for this asthma subtype. METHODS: We used electronic healthcare records linked to UK Biobank to identify asthma patients with high treatment burden and/or worse outcomes. We performed a genome-wide association study (GWAS) with this case population and healthy controls. We sought replication for associated (p≤5×10-6) signals in four independent studies (12 152 cases and 32 316 controls). Replicated signals were fine-mapped and linked to genes and pathways. RESULTS: In total, 7681 participants met our case definition and showed enrichment for adult-onset asthma, female gender and higher body mass index compared to asthma individuals not meeting case criteria. GWAS with 7681 cases and 38 405 controls revealed 21 reproducible association signals that had previously been associated with asthma, but had a larger effect size in our study. Variant-to-gene mapping highlighted 85 candidate genes, five of which were considered high confidence (BACH2, D2HGDH, IL1RL1, RPS26, SMAD3). CONCLUSION: We present the first use of electronic healthcare records in UK Biobank to identify a subtype of asthma enriched for patients with high treatment burden and/or worse outcomes. Our findings support the role of known asthma genes, highlighting genetic risk variants with stronger effect in these groups of patients. The prioritised genes provide potential therapeutic opportunities for this difficult-to-treat patient population.
Journal Article↗
Immunopathologic and morphologic studies of skeletal muscle in Chagas' disease.
Skeletal muscle biopsies from 21 individuals infected with Trypanosoma cruzi were studied my means of immunofluorescence, ultrastructural immunochemical, light and electron microscopic, and histochemical procedures. In 12 cases, definite morphologic alterations were found. These alterations were coincident with the presence of circulating antibodies against the plasma membrane of striated muscle fibers and endothelial cells (EVI antibodies). In almost all cases the lesions also presented autologous immunoglobulins bound to the plasma membrane of muscle fibers and endothelial cells. Interstitial inflammatory exudate was not observed in the diseased muscle. On the basis of these observations, it is suggested that the EVI antibody is related to some of the pathogenetic mechanism of skeletal muscle damage in Chagas' disease.
Adenosine Triphosphatases↗