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Hearing impairment (HI) is a prevalent neurosensory condition globally, impacting 5% of the population, with over 50% of congenital cases attributed to genetic etiologies. In Tunisia, HI underdiagnosis prevails, primarily due to limited access to comprehensive clinical tools, particularly for syndromic deafness (SD), characterized by clinical and genetic heterogeneity. This study aimed to uncover the SD spectrum through a 14-year investigation of a Tunisian cohort encompassing over 700 patients from four referral centers (2007-2021). Employing Sanger sequencing, Targeted Panel Gene Sequencing, and Whole Exome Sequencing, genetic analysis in 30 SD patients identified diagnoses such as Usher syndrome, Waardenburg syndrome, cranio-facial-hand-deafness syndrome, and H syndrome. This latter is a rare genodermatosis characterized by HI, hyperpigmentation, hypertrichosis, and systemic manifestations. A metaanalysis integrating our findings with existing data revealed that nearly 50% of Tunisian SD cases corresponded to rare inherited metabolic disorders. Distinguishing between non-syndromic and syndromic HI poses a challenge, where the age of onset and progression of features significantly impact accurate diagnoses. Despite advancements in local genetic characterization capabilities, certain ultra-rare forms of SD remain underdiagnosed. This research contributes critical insights to inform molecular diagnosis approaches for SD in Tunisia and the broader North-African region, thereby facilitating informed decision-making in clinical practice. [ABSTRACT FROM AUTHOR]

Hearing impairment (HI) is a prevalent neurosensory condition globally, impacting 5% of the population, with over 50% of congenital cases attributed to genetic etiologies. In Tunisia, HI underdiagnosis prevails, primarily due to limited access to comprehensive clinical tools, particularly for syndromic deafness (SD), characterized by clinical and genetic heterogeneity. This study aimed to uncover the SD spectrum through a 14-year investigation of a Tunisian cohort encompassing over 700 patients from four referral centers (2007-2021). Employing Sanger sequencing, Targeted Panel Gene Sequencing, and Whole Exome Sequencing, genetic analysis in 30 SD patients identified diagnoses such as Usher syndrome, Waardenburg syndrome, cranio-facial-hand-deafness syndrome, and H syndrome. This latter is a rare genodermatosis characterized by HI, hyperpigmentation, hypertrichosis, and systemic manifestations. A meta-analysis integrating our findings with existing data revealed that nearly 50% of Tunisian SD cases corresponded to rare inherited metabolic disorders. Distinguishing between non-syndromic and syndromic HI poses a challenge, where the age of onset and progression of features significantly impact accurate diagnoses. Despite advancements in local genetic characterization capabilities, certain ultra-rare forms of SD remain underdiagnosed. This research contributes critical insights to inform molecular diagnosis approaches for SD in Tunisia and the broader North-African region, thereby facilitating informed decision-making in clinical practice. [ABSTRACT FROM AUTHOR]

Hearing impairment (HI) is a prevalent neurosensory condition globally, impacting 5% of the population, with over 50% of congenital cases attributed to genetic etiologies. In Tunisia, HI underdiagnosis prevails, primarily due to limited access to comprehensive clinical tools, particularly for syndromic deafness (SD), characterized by clinical and genetic heterogeneity. This study aimed to uncover the SD spectrum through a 14-year investigation of a Tunisian cohort encompassing over 700 patients from four referral centers (2007–2021). Employing Sanger sequencing, Targeted Panel Gene Sequencing, and Whole Exome Sequencing, genetic analysis in 30 SD patients identified diagnoses such as Usher syndrome, Waardenburg syndrome, cranio-facial-hand-deafness syndrome, and H syndrome. This latter is a rare genodermatosis characterized by HI, hyperpigmentation, hypertrichosis, and systemic manifestations. A meta-analysis integrating our findings with existing data revealed that nearly 50% of Tunisian SD cases corresponded to rare inherited metabolic disorders. Distinguishing between non-syndromic and syndromic HI poses a challenge, where the age of onset and progression of features significantly impact accurate diagnoses. Despite advancements in local genetic characterization capabilities, certain ultra-rare forms of SD remain underdiagnosed. This research contributes critical insights to inform molecular diagnosis approaches for SD in Tunisia and the broader North-African region, thereby facilitating informed decision-making in clinical practice.

Fine needle aspiration cytology (FNAC) is a useful tool in the evaluation of lymphadenopathy. It is a safe and minimally invasive procedure that provides preoperative details for subsequent treatment. It can also diagnose the majority of malignant tumors. However, there are some instances where the diagnosis of tumors remains obscure. To address this, we re-analyzed the misinterpreted patients' samples using mRNA sequencing technology and then identified the characteristics of non-Hodgkin's lymphoma that tend to be under-diagnosed. To decipher the involved genes and pathways, we used bioinformatic and biological analysis approaches, identifying the response to oxygen species, inositol phosphate metabolic processes, and peroxisome and PPAR pathways as possibly being involved with this type of tumor. Notably, these analyses identified FOS, ENDOG, and PRKAR2B as hub genes. cBioPortal, a multidimensional cancer genomics database, also confirmed that these genes were associated with lymphoma patients. These results thus point to candidate genes that could be used as biomarkers to minimize the false-negative rate of FNAC diagnosis. We are currently pursuing the development of a gene chip to improve the diagnosis of lymphadenopathy patients with the ultimate goal of improving their prognosis. [ABSTRACT FROM AUTHOR]

Abstract Background Incidental carcinoma gall bladder and benign disease in radical cholecystectomy specimen is the cause of concern. We attempted to find out the incidence and reasons thereof in the present study. Methods Present study is a retrospective analysis of a prospectively maintained database between July 2002 and July 2019. All patients with a diagnosis of carcinoma gall bladder admitted for surgery were included. Results Out of 148 patients, 110 patients had carcinoma gall bladder (CAGB), while 38 patients (25.7%) had incidental carcinoma (under-diagnosis). Radical resection was done in 61/110 (55.4%) patients with clinical CAGB, where 15 (24.6%) patients had benign pathology (“over-diagnosis”). Overdiagnosis was due to xanthogranulomatous cholecystitis (n = 9), chronic cholecystitis (n = 2), tuberculosis (n = 2) and IgG4 related cholecystitis (n = 2). Among 61 patients, a history of weight loss and anorexia were significantly associated with malignancy. Asymmetrical wall thickness was significantly more common in benign mimickers. Among patients with incidental carcinoma, preoperative ultrasonography reported normal wall thickness of gall bladder in 28 (73.7%), thickened gall bladder wall in 6, and polyp in 3 patients. The resectability rate among incidental carcinoma was 27/38 (71.05%). Conclusion Over-diagnosis of the carcinoma gall bladder was present in 24.6%. On the other hand, incidental carcinoma comprised 25.7% of all admissions for carcinoma gall bladder with resectability of 71%.

Summary: Background: Autism has long been viewed as a paediatric condition, meaning that many autistic adults missed out on a diagnosis as children when autism was little known. We estimated numbers of diagnosed and undiagnosed autistic people in England, and examined how diagnostic rates differed by socio-demographic factors. Methods: This population-based cohort study of prospectively collected primary care data from IQVIA Medical Research Data (IMRD) compared the prevalence of diagnosed autism to community prevalence to estimate underdiagnosis. 602,433 individuals registered at an English primary care practice in 2018 and 5,586,100 individuals registered between 2000 and 2018 were included. Findings: Rates of diagnosed autism in children/young people were much higher than in adults/older adults. As of 2018, 2.94% of 10- to 14-year-olds had a diagnosis (1 in 34), vs. 0.02% aged 70+ (1 in 6000). Exploratory projections based on these data suggest that, as of 2018, 463,500 people (0.82% of the English population) may have been diagnosed autistic, and between 435,700 and 1,197,300 may be autistic and undiagnosed (59–72% of autistic people, 0.77%–2.12% of the English population). Age-related inequalities were also evident in new diagnoses (incidence): c.1 in 250 5- to 9-year-olds had a newly-recorded autism diagnosis in 2018, vs. c.1 in 4000 20- to 49-year-olds, and c.1 in 18,000 people aged 50+. Interpretation: Substantial age-related differences in the proportions of people diagnosed suggest an urgent need to improve access to adult autism diagnostic services. Funding: Dunhill Medical Trust, Economic and Social Research Council, Medical Research Council, National Institute for Health Research, the Wellcome Trust, and the Royal College of Psychiatrists.

Monkeypox is an emerging zoonotic disease caused by the monkeypox virus, which is an infectious agent belonging to the genus Orthopoxvirus. Currently, commencing from the end of April 2022, an outbreak of monkeypox is ongoing, with more than 43,000 cases reported as of 23 August 2022, involving 99 countries and territories across all the six World Health Organization (WHO) regions. On 23 July 2022, the Director-General of the WHO declared monkeypox a global public health emergency of international concern (PHEIC), since the outbreak represents an extraordinary, unusual, and unexpected event that poses a significant risk for international spread, requiring an immediate, coordinated international response. However, the real magnitude of the burden of disease could be masked by failures in ascertainment and under-detection. As such, underestimation affects the efficiency and reliability of surveillance and notification systems and compromises the possibility of making informed and evidence-based policy decisions in terms of the adoption and implementation of ad hoc adequate preventive measures. In this review, synthesizing 53 papers, we summarize the determinants of the underestimation of sexually transmitted diseases, in general, and, in particular, monkeypox, in terms of all their various components and dimensions (under-ascertainment, underreporting, under-detection, under-diagnosis, misdiagnosis/misclassification, and under-notification). [ABSTRACT FROM AUTHOR]

Background: Incidental carcinoma gall bladder and benign disease in radical cholecystectomy specimen is the cause of concern. We attempted to find out the incidence and reasons thereof in the present study.Methods: Present study is a retrospective analysis of a prospectively maintained database between July 2002 and July 2019. All patients with a diagnosis of carcinoma gall bladder admitted for surgery were included.Results: Out of 148 patients, 110 patients had carcinoma gall bladder (CAGB), while 38 patients (25.7%) had incidental carcinoma (under-diagnosis). Radical resection was done in 61/110 (55.4%) patients with clinical CAGB, where 15 (24.6%) patients had benign pathology ("over-diagnosis"). Overdiagnosis was due to xanthogranulomatous cholecystitis (n = 9), chronic cholecystitis (n = 2), tuberculosis (n = 2) and IgG4 related cholecystitis (n = 2). Among 61 patients, a history of weight loss and anorexia were significantly associated with malignancy. Asymmetrical wall thickness was significantly more common in benign mimickers. Among patients with incidental carcinoma, preoperative ultrasonography reported normal wall thickness of gall bladder in 28 (73.7%), thickened gall bladder wall in 6, and polyp in 3 patients. The resectability rate among incidental carcinoma was 27/38 (71.05%).Conclusion: Over-diagnosis of the carcinoma gall bladder was present in 24.6%. On the other hand, incidental carcinoma comprised 25.7% of all admissions for carcinoma gall bladder with resectability of 71%. [ABSTRACT FROM AUTHOR]

Fine needle aspiration cytology (FNAC) is a useful tool in the evaluation of lymphadenopathy. It is a safe and minimally invasive procedure that provides preoperative details for subsequent treatment. It can also diagnose the majority of malignant tumors. However, there are some instances where the diagnosis of tumors remains obscure. To address this, we re-analyzed the misinterpreted patients’ samples using mRNA sequencing technology and then identified the characteristics of non-Hodgkin’s lymphoma that tend to be under-diagnosed. To decipher the involved genes and pathways, we used bioinformatic and biological analysis approaches, identifying the response to oxygen species, inositol phosphate metabolic processes, and peroxisome and PPAR pathways as possibly being involved with this type of tumor. Notably, these analyses identified FOS, ENDOG, and PRKAR2B as hub genes. cBioPortal, a multidimensional cancer genomics database, also confirmed that these genes were associated with lymphoma patients. These results thus point to candidate genes that could be used as biomarkers to minimize the false-negative rate of FNAC diagnosis. We are currently pursuing the development of a gene chip to improve the diagnosis of lymphadenopathy patients with the ultimate goal of improving their prognosis.

Abstract Background Despite widespread use, the accuracy of the diagnostic test for SARS-CoV-2 infection is poorly understood. The aim of our work was to better quantify misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves using publicly available surveillance data from Alberta, Canada and Philadelphia, USA. Methods We examined time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, the sensitivity and specificity of the diagnostic test. Results Our analysis revealed that the data were compatible with near-perfect specificity, but it was challenging to gain information about sensitivity. We applied these insights to uncertainty/bias analysis of epidemic curves under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the adjusted epidemic curves likely falls within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60–70% range. In the extreme scenario, hundreds of undiagnosed cases, even among the tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate. Conclusion The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves.

Following stroke, individuals require ongoing screening, diagnosis and monitoring for cognitive impairment. Services and policies around these vary widely between settings, and reports from many countries highlight persistent under-diagnosis of cognitive impairment in the months and years after stroke. Missed and delayed diagnosis of post-stroke cognitive impairment, including dementia, are important factors in shaping the experiences of people so affected and their family members, especially in low- and middle-income countries. Drawing upon ethnographic research conducted in Malaysia, this article draws upon three case studies to examine the continued health-seeking behaviour after the appearance of salient cognitive and behavioural symptoms that occurred after stroke. Findings highlight the challenges in getting formal diagnostic clarity for cognitive and behavioural symptoms in a rural setting within a middle-income country. No study participants sought help for memory or cognitive problems, partly due to limited lay awareness of cognitive impairment but more significantly due to health service factors. Despite their elevated risk for dementia, participants were not monitored for cognitive impairment during any follow-up care in various health facilities. Furthermore, caregivers' attempts to seek help when behavioural issues became untenable were met with multiple health system barriers. The journey was complicated by the meanings attached to the reactions towards cognitive symptoms at the community level. We suggest that strategies seek to increase the awareness of post-stroke cognitive and behavioural symptoms, and incorporate clear treatment pathways into the long-term care plans of community-dwelling stroke survivors.

Following stroke, individuals require ongoing screening, diagnosis and monitoring for cognitive impairment. Services and policies around these vary widely between settings, and reports from many countries highlight persistent under-diagnosis of cognitive impairment in the months and years after stroke. Missed and delayed diagnosis of post-stroke cognitive impairment, including dementia, are important factors in shaping the experiences of people so affected and their family members, especially in low- and middle-income countries. Drawing upon ethnographic research conducted in Malaysia, this article draws upon three case studies to examine the continued health-seeking behaviour after the appearance of salient cognitive and behavioural symptoms that occurred after stroke. Findings highlight the challenges in getting formal diagnostic clarity for cognitive and behavioural symptoms in a rural setting within a middle-income country. No study participants sought help for memory or cognitive problems, partly due to limited lay awareness of cognitive impairment but more significantly due to health service factors. Despite their elevated risk for dementia, participants were not monitored for cognitive impairment during any follow-up care in various health facilities. Furthermore, caregivers' attempts to seek help when behavioural issues became untenable were met with multiple health system barriers. The journey was complicated by the meanings attached to the reactions towards cognitive symptoms at the community level. We suggest that strategies seek to increase the awareness of post-stroke cognitive and behavioural symptoms, and incorporate clear treatment pathways into the long-term care plans of community-dwelling stroke survivors. [ABSTRACT FROM AUTHOR]

Objective: Attention Deficit Hyperactivity/Impulsivity Disorder (ADHD) is one of the most common learning difficulties in Chilean schools. It is characterized by an atypical functioning pattern in attention and inhibition, strongly compromising other executive functions. One of the challenges posed by this disorder is the diagnosis process, which is often not sufficiently accurate. The intention is to study the distribution of two students samples, with and without ADHD, diagnosed by a behavioral observation scale through the evaluation of attention, inhibition, and cognitive flexibility executive functions. Method: This study evaluated 132 students, 66 with ADHD and 66 without ADHD, considering the attention, inhibition, and cognitive flexibility variables of a school in the city of Concepción in Chile. Cognitive performance was contrasted with the diagnoses, and students were regrouped in the disorder known subtypes. Results: The neuropsychological evaluation showed that in the ADHD group, there were students who did not meet the diagnostic criteria to be included in the group. A similar phenomenon was observed in the group without ADHD. In both the groups, the neuropsychological evaluation of attention and inhibition was useful in providing a more certain dignosis and in determining the subtype to which each student detected with ADHD belonged. Cognitive flexibility was only useful in differentiating betwen the subjects with and without ADHD. Conclusions: In both the groups studied, it was possible to find misdiagnosed subjects; the overdiagnosis was 43,93% in the ADHD group, while the under-diagnosis was 42,42% in the group without ADHD. [ABSTRACT FROM AUTHOR]

Background: Despite widespread use, the accuracy of the diagnostic test for SARS-CoV-2 infection is poorly understood. The aim of our work was to better quantify misclassification errors in identification of true cases of COVID-19 and to study the impact of these errors in epidemic curves using publicly available surveillance data from Alberta, Canada and Philadelphia, USA.Methods: We examined time-series data of laboratory tests for SARS-CoV-2 viral infection, the causal agent for COVID-19, to try to explore, using a Bayesian approach, the sensitivity and specificity of the diagnostic test.Results: Our analysis revealed that the data were compatible with near-perfect specificity, but it was challenging to gain information about sensitivity. We applied these insights to uncertainty/bias analysis of epidemic curves under the assumptions of both improving and degrading sensitivity. If the sensitivity improved from 60 to 95%, the adjusted epidemic curves likely falls within the 95% confidence intervals of the observed counts. However, bias in the shape and peak of the epidemic curves can be pronounced, if sensitivity either degrades or remains poor in the 60-70% range. In the extreme scenario, hundreds of undiagnosed cases, even among the tested, are possible, potentially leading to further unchecked contagion should these cases not self-isolate.Conclusion: The best way to better understand bias in the epidemic curves of COVID-19 due to errors in testing is to empirically evaluate misclassification of diagnosis in clinical settings and apply this knowledge to adjustment of epidemic curves. [ABSTRACT FROM AUTHOR]

Introduction The presented study of 4,535 children aged 7–17 years in the Upper Silesian region of Poland yielded 186 cases of previously known asthma, and 44 children with newly diagnosed asthma. The aim of the presented study was to identify non-medical factors that could explain why children with a newly established diagnosis (‘undiagnosed asthma’) had not been diagnosed in the past. Material and Methods The study was performed according to a case-control design. Parents of the children answered questionnaires on socio-economic status and family-related factors. Statistical determinants of undiagnosed asthma were explored using raw (OR) and logistic odds ratios with their 95% confidence intervals (logOR, 95%CI). Results Children with undiagnosed asthma were younger compared to the group with previously known asthma (11.3±2.1 vs. 12.6±2.5 years; p=0.0008). Newly diagnosed cases were more frequent in children who had less parental attention (less than 1 hour/day spent by parent with child – OR=4.36; 95%CI: 1.76–10.81) and who were not registered with specialized health care (OR=2.20; 95%CI: 0.95–5.06). Results of logistic regression analysis suggest that under-diagnosis of asthma is related to age below 12 years – logOR = 3.59 (95%CI: 1.28–10.36), distance to a health centre > 5 km – logOR = 3.45 (95%CI: 1.05–11.36), time spent with child < 1 hour/day – logOR = 6.28 (95%CI: 1.98–19.91). Conclusions Among non-medical determinants of undiagnosed asthma the age of a child plays a major role. Another factors of importance is the large distance between residence and health centre, and low parental attention at home.

Thomas R Skinner,1 Ian A Scott,2,3 Jennifer H Martin3,4 1Department of Internal Medicine, Sunshine Coast Health Service District, Nambour Hospital, Nambour, QLD, Australia; 2Internal Medicine and Clinical Epidemiology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia; 3Southern School of Medicine, University of Queensland, Brisbane, QLD, Australia; 4School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia Background: Misdiagnosis, either over- or underdiagnosis, exposes older patients to increased risk of inappropriate or omitted investigations and treatments, psychological distress, and financial burden. Objective: To evaluate the frequency and nature of diagnostic errors in 16 conditions prevalent in older patients by undertaking a systematic literature review. Data sources and study selection: Cohort studies, cross-sectional studies, or systematic reviews of such studies published in Medline between September 1993 and May 2014 were searched using key search terms of “diagnostic error”, “misdiagnosis”, “accuracy”, “validity”, or “diagnosis” and terms relating to each disease. Data synthesis: A total of 938 articles were retrieved. Diagnostic error rates of >10% for both over- and underdiagnosis were seen in chronic obstructive pulmonary disease, dementia, Parkinson’s disease, heart failure, stroke/transient ischemic attack, and acute myocardial infarction. Diabetes was overdiagnosed in

Mucoepidermoid Carcinoma (MEC) is the most common malignant neoplasm of salivary gland origin. However, its morphologic heterogeneity poses difficulty in interpretation. In the present series we discuss the morphologic features of MEC, limitations and pitfalls in its diagnosis on Fine Needle Aspiration Cytology (FNAC). Fourteen cases of suspected MEC were evaluated cytologically followed by histopathological examination for confirmation. A definite cytological diagnosis was rendered in nine cases; three of the remaining five were underdiagnosed as abscess, pleomorphic adenoma and mucus cyst. Of the remaining two cases, one case each of sebaceous carcinoma and sialadenitis was mislabeled as MEC on cytology. A satisfactory aspirate composed of intermediate cells, mucin secreting cells and squamous cells in a mucinous background may not be obtained in all cases of low grade MEC. High grade MEC can be classified as squamous cell carcinoma. Hence, awareness of confounding factors with clinicopathologic correlation and judicious use of frozen section can help in minimizing errors.

Within research into neurodevelopmental disorders, little is known about the mechanisms underpinning changes in symptom severity across development. When the behavioural presentation of a condition improves/symptoms lessen, this may be because core underlying atypicalities in cognition/neural function have ameliorated. An alternative possibility is ‘compensation’; that the behavioural presentation appears improved, despite persisting deficits at cognitive and/or neurobiological levels. There is, however, currently no agreed technical definition of compensation or its behavioural, cognitive and neural characteristics. Furthermore, its workings in neurodevelopmental disorders have not been studied directly. Here, we review current evidence for compensation in neurodevelopmental disorders, using Autism Spectrum Disorder as an example, in order to move towards a better conceptualisation of the construct. We propose a transdiagnostic framework, where compensation represents the processes responsible for an observed mismatch between behaviour and underlying cognition in a neurodevelopmental disorder, at any point in development. Further, we explore potential cognitive and neural mechanisms driving compensation and discuss the broader relevance of the concept within research and clinical settings. [ABSTRACT FROM AUTHOR]

Introduction. The presented study of 4,535 children aged 7-17 years in the Upper Silesian region of Poland yielded 186 cases of previously known asthma, and 44 children with newly diagnosed asthma. The aim of the presented study was to identify non-medical factors that could explain why children with a newly established diagnosis ('undiagnosed asthma') had not been diagnosed in the past. Materials and method. The study was performed according to a case-control design. Parents of the children answered questionnaires on socio-economic status and family-related factors. Statistical determinants of undiagnosed asthma were explored using raw (OR) and logistic odds ratios with their 95% confidence intervals (logOR, 95%CI). Results. Children with undiagnosed asthma were younger compared to the group with previously known asthma (11.3±2.1 vs. 12.6±2.5 years; p=0.0008). Newly diagnosed cases were more frequent in children who had less parental attention (less than 1 hour/day spent by parent with child - OR=4.36; 95%CI: 1.76-10.81) and who were not registered with specialized health care (OR=2.20; 95%CI: 0.95-5.06). Results of logistic regression analysis suggest that under-diagnosis of asthma is related to age below 12 years - logOR = 3.59 (95%CI: 1.28-10.36), distance to a health centre > 5 km - logOR = 3.45 (95%CI: 1.05-11.36), time spent with child < 1 hour/day - logOR = 6.28 (95%CI: 1.98-19.91). Conclusion. Among non-medical determinants of undiagnosed asthma the age of a child plays a major role. Another factors of importance is the large distance between residence and health centre, and low parental attention at home. [ABSTRACT FROM AUTHOR]

Background: Autism has long been viewed as a paediatric condition, meaning that many autistic adults missed out on a diagnosis as children when autism was little known. We estimated numbers of diagnosed and undiagnosed autistic people in England, and examined how diagnostic rates differed by socio-demographic factors., Methods: This population-based cohort study of prospectively collected primary care data from IQVIA Medical Research Data (IMRD) compared the prevalence of diagnosed autism to community prevalence to estimate underdiagnosis. 602,433 individuals registered at an English primary care practice in 2018 and 5,586,100 individuals registered between 2000 and 2018 were included., Findings: Rates of diagnosed autism in children/young people were much higher than in adults/older adults. As of 2018, 2.94% of 10- to 14-year-olds had a diagnosis (1 in 34), vs. 0.02% aged 70+ (1 in 6000). Exploratory projections based on these data suggest that, as of 2018, 463,500 people (0.82% of the English population) may have been diagnosed autistic, and between 435,700 and 1,197,300 may be autistic and undiagnosed (59-72% of autistic people, 0.77%-2.12% of the English population). Age-related inequalities were also evident in new diagnoses (incidence): c.1 in 250 5- to 9-year-olds had a newly-recorded autism diagnosis in 2018, vs. c.1 in 4000 20- to 49-year-olds, and c.1 in 18,000 people aged 50+., Interpretation: Substantial age-related differences in the proportions of people diagnosed suggest an urgent need to improve access to adult autism diagnostic services., Funding: Dunhill Medical Trust, Economic and Social Research Council, Medical Research Council, National Institute for Health Research, the Wellcome Trust, and the Royal College of Psychiatrists., Competing Interests: E.O. received a post-doctoral fellowship from the Dunhill Medical Trust which funded completion of the work (grant awarded to J.S., W.M., I.P., R.C., C.C., F.H., A.C., J.M., M.R., and C.Z.). J.S. was supported by the ESRC and NIHR. M.R. was supported by the Medical Research Council and J.E.J.B. was supported by the Wellcome Trust and the Royal College of Psychiatrists. R.S. declares no support from any organisation for the submitted work. J.M. was supported by the NIHR Applied Research Collaboration (ARC) South London. WM was supported by the MRC and NIHR. The views expressed are those of the authors and not necessarily those of the NHS, NIHR, the Wellcome Trust, the Dunhill Medical Trust, the ESRC, or the MRC. All authors declare that they have no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work., (© 2023 The Author(s).)

The chronic hepatitis C ( CHC) cohort in the United States is getting older. Elderly patients with CHC may be at a high risk of cirrhosis and hepatocellular carcinoma ( HCC), but also other nonhepatic comorbidities that negatively impact their likelihood of receiving or responding to antiviral treatment. There is little information on the clinical epidemiology or outcomes of CHC and its treatment in the elderly. We conducted a retrospective cohort study of 1 61 744 patients with a positive Hepatitis C virus RNA in the Veterans Health Administration Hepatitis C Clinical Case Registry to examine the association between age subgroups (20-49, 50-64, 65-85 years) and risk of cirrhosis, HCC or death using Cox proportional hazards models. We also examined the effect of treatment with a sustained viral response ( SVR) on these outcomes in each age subgroup. The age distribution was 36.8% 20- to 49-year-olds, 57.6% 50- to 64-year-olds and 5.6% 65- to 85-year-olds (i.e. elderly). Risk of cirrhosis, HCC and death was significantly elevated in elderly patients [ HR cirrhosis = 1.14 (1.00-1.29), HR HCC = 2.44 (1.99-2.99); HR death 2.09 (1.98-2.22)] compared with younger patients. The incidence of HCC was than 8.4 per 1000 PY in the elderly compared with 2.6 per 1000 PY and 5.7 per 1000 PY, among the 20-49 and 50-64 age groups, respectively. Elderly patients were significantly less likely to receive antiviral treatment (3.8% vs 14.8% and 19.1%, P < 0.0001), but among those who received treatment SVR was not different among the age groups (33.5% vs 33.2% and 32.1%). In an analysis limited to those who received treatment, SVR compared to treatment receipt with no SVR was associated with a reduction in risk of developing cirrhosis ( HR = 0.34; 0.18-0.66) and HCC ( HR = 0.60; 0.22-1.61) and all-cause mortality risk ( HR = 0.52, 0.33-0.82). Elderly patients with CHC are more likely to develop HCC than younger patients but have traditionally received less antiviral treatment than younger patients. However, receipt of curative treatment is associated with a benefit in reducing cirrhosis, HCC and overall mortality, irrespective of age. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the correlation between MMSE ≤ 23 and the presence of a diagnosis of dementia in the medical record in a population with multimorbidity. Design, setting, and participants: This cross-sectional study was part of the Ambulatory Geriatric Assessment - a Frailty Intervention Trial (AGe-FIT; N = 382). Participants were community dwelling, aged ≥ 75 years, had received inpatient hospital care at least three times during the past 12 months, and had three or more concomitant diagnoses according to the International Classification of Diseases, 10th revision. Measurements: The Mini Mental State Examination (MMSE) was administered at baseline. Medical records of participants with MMSE scores < 24 were examined for the presence of dementia diagnoses and two years ahead. Results: Fifty-three (16%) of 337 participants with a measure of MMSE had a MMSE scores < 24. Six of these 53 (11%) participants had diagnoses of dementia (vascular dementia, n = 4; unspecified dementia, n = 1; Alzheimers disease, n = 1) according to medical records; 89% did not. Conclusions: A MMSE-score < 24 is not well correlated to a diagnosis of dementia in the medical record in a population of elderly with multimorbidity. This could imply that cognitive decline and the diagnosis of dementia remain undetected in older people with multimorbidity. Proactive care of older people with multimorbidity should focus on cognitive decline to detect cognitive impairment and to provide necessary help and support to this very vulnerable group. [ABSTRACT FROM AUTHOR]

Asymptomatic conditions such as hypertension are generally hard to diagnose, absent routine medical examinations. This is especially problematic in developing countries, where most citizens do not engage in routine examinations due to limited economic resources. We study the roles of education and individual time preferences in asymptomatic disease detection and management. Using discrete choice models on a sample of 4209 hypertensive Indonesian adults surveyed between November 2007 and April 2008, we find that both education and individual time preferences play important roles. However, the effects are different for people in good health than they are for people in bad health. Education does not seem to matter for disease detection when respondents are in good general health, and its effects on disease management vary largely in magnitudes between these groups. In terms of disease detection, more educated respondents have a higher probability of being diagnosed, but only conditional on being in poor general health. Time preferences, on the other hand, matter for respondents in good general health, but the effect is not significant for those in bad health. More impatient respondents that are in good health have a higher probability of being under-diagnosed because they are more likely to forgo routine physicals. The findings point to two distinct channels through which education can affect health, and suggest that different types of policies need to be implemented, in order to reach the entire population. Traditional programs that stimulate education and improve the socio-economic status of individuals in developing countries are helpful, but they do not address the whole problem. Besides its more usual positive effects, education can also negatively affect the health of asymptomatic patients, because it reflects a higher opportunity cost of engaging in preventative health screenings. [ABSTRACT FROM AUTHOR]

Mucoepidermoid Carcinoma (MEC) is the most common malignant neoplasm of salivary gland origin. However, its morphologic heterogeneity poses difficulty in interpretation. In the present series we discuss the morphologic features of MEC, limitations and pitfalls in its diagnosis on Fine Needle Aspiration Cytology (FNAC). Fourteen cases of suspected MEC were evaluated cytologically followed by histopathological examination for confirmation. A definite cytological diagnosis was rendered in nine cases; three of the remaining five were underdiagnosed as abscess, pleomorphic adenoma and mucus cyst. Of the remaining two cases, one case each of sebaceous carcinoma and sialadenitis was mislabeled as MEC on cytology. A satisfactory aspirate composed of intermediate cells, mucin secreting cells and squamous cells in a mucinous background may not be obtained in all cases of low grade MEC. High grade MEC can be classified as squamous cell carcinoma. Hence, awareness of confounding factors with clinicopathologic correlation and judicious use of frozen section can help in minimizing errors. [ABSTRACT FROM AUTHOR]

Background Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease, is considered under-diagnosed. Our primary objective was to provide evidence of under-diagnosis of HHT in a North American population. We hypothesized that variation would exist in the diagnosed prevalence (D-prevalence) across regions in the province of Ontario, Canada and across age groups, due to under-diagnosis in certain groups. Our secondary objective was to collect data regarding contact and local access to consult specialists by HHT patients to help guide potential future diagnostic programs. Methods Primary objective- 556 adult patients with definite HHT diagnosis seen at the Toronto HHT Centre were identified and geocoded with postal codes. Prevalence rates were calculated using Canadian census data. Secondary objective- A driving network model was developed in ArcGIS. Service area buffers around ear, nose and throat (ENT) clinics in Ontario were generated to evaluate the proportion of the Ontario population with access to these clinics. A survey was also sent to the email contact list of HHT Foundation International, targeting people with diagnosed HHT, regarding consultation with ENT physicians for epistaxis and timing of HHT diagnosis. Results Primary objective- D-prevalence rates varied among regions, from no cases to 1.1 cases per 5000 in large Ontario cities. There were no significant differences between urban and rural prevalence rates. Variation in prevalence was seen across age groups, with greater prevalence in older adults (≥50 years-old) compared with adults 20–49 years-old (0.36 versus 0.26 per 5000, p < 0.0005). Secondary objective- Most Ontarians had access to ENT clinics within a 30, 60 and 90 minute modeled drive time (92.7 %, 97.8 % and 98.6 %, respectively). Nearly 40 % of surveyed patients consulted an ENT physician for their epistaxis, on average 13.9 ± 12.2 years prior to being diagnosed with HHT. Conclusions The prevalence of HHT in Ontario is highly variable across regions and age-groups, suggesting under-diagnosis. Given that patients with HHT frequently consult ENT physicians for epistaxis prior to HHT diagnosis, and that there is almost universal access to ENTs in Ontario, we propose targeting ENT clinics as a province-wide approach to detect undiagnosed HHT patients and families. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency with which bipolar II disorder (BD II) was diagnosed in clinics held in four rural towns in New South Wales (NSW). Method: A retrospective case file audit was conducted for patients referred for psychiatric assessment and treatment in four towns in rural NSW over a period of two years and nine months. Results: Of 559 patients seen for the first time during the study period, 113 (20.2%) were diagnosed with BD II, and of these this diagnosis was made for the first time in 69 patients (61%). Associated clinical findings in BD II patients are presented and a comparison is made with patients with non-bipolar depression seen during the same period. Conclusion: BD II was commonly seen in these rural clinics, and appears to be often under-diagnosed in general practice, as has been found to be the case in urban centres. This is seen as a serious public health problem, which needs to be addressed by educational steps directed at general practitioners (GPs), mental health clinicians, and perhaps also the general public. [ABSTRACT FROM AUTHOR]

Bacterial pneumonia has hitherto been considered the key cause of the high respiratory morbidity and mortality in children under five years of age (under-5s) in low-income countries, while asthma has not been stated as a significant reason. This paper explores the definitions and concepts of pneumonia and asthma/wheezing/bronchiolitis and examines whether asthma in under-5s may be confused with pneumonia. Over-diagnosing of bacterial pneumonia can be suspected from the limited association between clinical pneumonia and confirmatory test results such as chest x-ray and microbiological findings and poor treatment results using antibiotics. Moreover, children diagnosed with recurrent pneumonia in infancy were often later diagnosed with asthma. Recent studies showed a 10-15% prevalence of preschool asthma in low-income countries, although under-5s with long-term cough and difficulty breathing remain undiagnosed. New studies demonstrate that approximately 50% of acutely admitted under-5s diagnosed with pneumonia according to Integrated Management of Childhood Illnesses could be re-diagnosed with asthma or wheezing when using re-defined diagnostic criteria and treatment. It is hypothesised that untreated asthma may contribute to respiratory mortality since respiratory syncytial virus (RSV) is an important cause of respiratory death in childhood, and asthma in under-5s is often exacerbated by viral infections, including RSV. Furthermore, acute respiratory treatment failures were predominantly seen in under-5s without fever, which suggests the diagnosis of asthma/wheezing rather than bacterial pneumonia. Ultimately, underlying asthma may have contributed to malnutrition and fatal bacterial pneumonia. In conclusion, preschool asthma in low-income countries may be significantly under-diagnosed and misdiagnosed as pneumonia, and may be the cause of much morbidity and mortality. [ABSTRACT FROM AUTHOR]

Abstract: Despite growing concerns of over-treatment, the under-diagnosis and undertreatment of major depressive disorders is still prevalent. Causal attributions are thought to be involved in help seeking behavior, time to diagnosis and the chance for successful referral. Yet, little is known about the extent to which these processes are influenced by causal attributions. 120 patients, involved in the nationwide second Dutch National Survey of General Practice (), with a current DSM-IV diagnosis of depression, severe depression or with a depression lasting over six months, completed a causal attributions inventory. Demographic and clinical data from the survey, and causal attribution scores were used as independent variables in association with getting a diagnosis of depression from the general practitioner, or being in treatment by a mental health care provider for more than 3 sessions. Causal attributions related to intrapsychic fears were significantly associated with getting a diagnosis of depression and successful referral. Causal attributions related to childhood were also positively associated with successful referral. In association models derived from all the demographic and clinical data available in the survey, causal attributions substantially contributed to the explained variance, 55% and 39% respectively. The findings suggest causal attributions have a statistically significant impact on time to diagnosis and the chance of successful referral. Using the Causal Attribution Inventory with high-risk patients in primary care might enhance the chance of detection and successful referral of depressed patients. Schellevis, F. G., Westert, G. P., & De Bakker, D. H. (2005). The actual role of general practice in the dutch health-care system. Results of the second dutch national survey of general practice. Medizinische Klinik (Munich), 100(10), 656–661. [Copyright &y& Elsevier]

Chronic kidney disease (CKD) is a major health problem. Recent emphasis has been to prevent the progression of CKD. We used chart audits to see if CKD was an under-recognized condition in a general medicine resident clinic. Data focused on recognition of CKD, 3 or 4, evaluation of metabolic bone disease, and anemia. A multifaceted educational initiative was developed and occurred between 2005 and 2010. Three retrospective chart audits were performed, in 2005 prior to the education and again in 2007 and 2010. In 2005, less than one-fifth of patients were identified as CKD, 3 or 4. Evaluation of bone disease and anemia is similar. Initial results were reviewed with the residents and handouts for metabolic bone monitoring were developed. Wall charts of the handouts were also posted. In 2007, CKD recognition increased slightly, but more patients had bone disease and anemia evaluations. After 2007, the only educational intervention was a CKD lecture given yearly. In 2010, the audit saw decreased recognition of CKD and a decline in metabolic bone monitoring. Although complete blood count (CBC) monitoring decreased, iron studies increased to 50%% of patients. We conclude that despite educational initiatives and re-enforcement efforts with the internal medicine residents and attending staff, major issues related to CKD are not being recognized or addressed. With an increasing CKD population, attempts must be made to improve recognition and management. Novel strategies need to be developed. [ABSTRACT FROM AUTHOR]

Abstract: Among pre-invasive breast diseases, the lesion of flat epithelial atypia has a level of risk that remains unclear. The clinical significance of these lesions and how to behave during their diagnostic biopsy (monitoring vs. surgery) are still uncertain, because few studies (including monitoring) are available and because of the polymorphic spectrum of lesions and their many denominations across the studies in the literature. This article aims to update our knowledge and provide elements for the management of these lesions diagnosed on breast biopsy. [Copyright &y& Elsevier]

OBJECTIVES To evaluate possible over- and under-diagnosis of prostate cancer in a screened vs a referral population in the same range of prostate-specific antigen (PSA). PATIENTS AND METHODS In all, 1445 patients undergoing radical prostatectomy and with a PSA level of <10 ng/mL were evaluated; 237 were from outside Tyrol (Austria) and represented the unscreened group, and 1208 were Tyrolean screening volunteers. Over-diagnosis was defined as a pathological stage of pT2a and a Gleason score of <7 with no positive surgical margins. Under-diagnosis was defined as a pathological stage of ≥pT3a or positive surgical margins. The chi-square test was used to assess the differences, with P < 0.05 considered to indicate statistical significance. RESULTS There were no significant differences in patient age or PSA levels between the study groups. There was over-diagnosis in the screening and referral groups in 17.4% and 8.9%, respectively, and under-diagnosis in 18.6% and 42.2%, respectively. CONCLUSION This study suggests that patients with prostate cancer participating in a screening programme are less likely to be under-diagnosed or have extracapsular disease than their counterparts in a referral population, even in the same PSA range, after radical prostatectomy. Furthermore, there was more under-diagnosis in the referral group than over-diagnosis in the screened group. [ABSTRACT FROM AUTHOR]

Abstract Background Under-diagnosis and under-treatment of childhood asthma were investigated in France using data collected during the 6 Cities Study, the French contribution to the International Study of Asthma and Allergies in Childhood. Methods 7,781 schoolchildren aged between 9 and 10 years underwent a medical visit including skin prick tests to common allergens and exercise test for Exercise-Induced Asthma (EIA) and their parents filled in a standardized questionnaire on asthma, management, treatment and potential risk factors. Results 903 children reported asthma (11.6%), 377 without a doctor’s diagnosis. Of the 526 participants with a diagnosis of asthma confirmed by a doctor (58.2%), 353 were treated and 76 were not treated during the year preceding the investigation despite their diagnosis. The information on the treatment was missing for the rest of individuals diagnosed with asthma (n = 97). Having a treatment was significantly associated with severe asthma and with the presence of other respiratory and allergic stigmata (atopic eczema, rhinitis, positive skin allergy tests, and EIA). In addition, having a treatment did not correspond to a good control of the disease. Similarly, children with asthma-like symptoms but without doctor-diagnosed asthma had asthma less well controlled than children with diagnosed asthma. They were also more exposed to passive smoking and traffic but had fewer pets. In contrast, diagnosed children reported more frequently a small weight at birth and a preterm birth. Conclusions In France, childhood asthma is still under-diagnosed and under-treated and environmental factors play a role in these phenomena.

The article offers information on a study related to the patients of Human T cell Lymphotropic Virus type 1 (HTLV-1). Topics discussed include study of T cell Non-Hodgkin lymphomas of patients from Netherlands; under-diagnosis of Adult T cell leukaemia/lymphoma; and the study related to the patients born in high HTLV-1 endemic countries such as Surinam, Netherlands and Ghana.

Recently, the "Choosing Wisely" initiative has gained traction and high-value care has garnered attention. However, the actual situation of high-value care is different between developed and developing countries. To elucidate this, we highlight the differences between the high-value care provided by healthcare systems in Japan and Myanmar, as representations of developed and developing countries, respectively. Despite the total numbers of magnetic resonance imaging (MRI) equipment in Japan being 400 times higher than in Myanmar, and gross domestic product per capita being 32 times higher in Japan, the individual costs (out of pocket expenditures) per MRI scan are the same (USD 60). However, the total cost per MRI scan is different, implying that differing healthcare costs indicate the existence of over- and under-diagnosis problems among different countries. This study suggests that detailed patient histories and physical examinations are important for selecting relevant diagnostic imaging and reducing unnecessary imaging., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Watari et al.)