Definition Of Disease Research Articles

Approach for defining human adenovirus infection and disease for central review adjudication in clinical studies.

Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR. Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease.

European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4)

IntroductionThe OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). MethodsGuidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. ResultsModerate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended. DiscussionThese multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.

Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas: A RANO review.

The utility of liquid biopsies is well documented in several extracranial and intracranial (brain/leptomeningeal metastases, gliomas) tumors. The RANO (Response Assessment in Neuro-Oncology) group has set up a multidisciplinary Task Force to critically review the role of blood and cerebrospinal fluid (CSF)-liquid biopsy in CNS lymphomas, with a main focus on primary central nervous system lymphomas (PCNSL). Several clinical applications are suggested: diagnosis of PCNSL in critical settings (elderly or frail patients, deep locations, and steroid responsiveness), definition of minimal residual disease, early indication of tumor response or relapse following treatments, and prediction of outcome. Thus far, no clinically validated circulating biomarkers for managing both primary and secondary CNS lymphomas exist. There is need of standardization of biofluid collection, choice of analytes, and type of technique to perform the molecular analysis. The various assays should be evaluated through well-organized central testing within clinical trials.

MAFLD as part of systemic metabolic dysregulation.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. In recent years, a new terminology and definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. Compared to the NAFLD definition, MAFLD better emphasizes the pathogenic role of metabolic dysfunction in the development and progression of this highly prevalent condition. Metabolic disorders, including overweight/obesity, type 2 diabetes mellitus (T2DM), atherogenic dyslipidemia and hypertension, are often associated with systemic organ dysfunctions, thereby suggesting that multiple organ damage can occur in MAFLD. Substantial epidemiological evidence indicates that MAFLD is not only associated with an increased risk of liver-related complications, but also increases the risk of developing several extra-hepatic diseases, including new-onset T2DM, adverse cardiovascular and renal outcomes, and some common endocrine diseases. We have summarized the current literature on the adverse effect of MAFLD on the development of multiple extrahepatic (cardiometabolic and endocrine) complications and examined the role of different metabolic pathways and organ systems in the progression of MAFLD, thus providing new insights into the role of MAFLD as a multisystem metabolic disorder. Our narrative review aimed to provide insights into potential mechanisms underlying the known associations between MAFLD and extrahepatic diseases, as part of MAFLD as a multisystem disease, in order to help focus areas for future drug development targeting not only liver disease but also the risk of extrahepatic complications.

Latest Trend and Perspective of Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) as a Novel Nomenclature

Recently, the medical term for nonalcoholic fatty liver disease (NAFLD) has been changed to a novel nomenclature: metabolic dysfunction-associated steatotic liver disease (MASLD). The latest report shows analyses of the National Health and Nutrition Examination Survey (NHANES III) using the fibrosis-4 index (FIB-4) and enhanced liver fibrosis (ELF). Among 6429 NAFLD cases, 99% met MASLD criteria. In another study with 4286 cases, 99% of steatosis cases met the MASLD definition, and 95.4% met the metabolic dysfunction-associated fatty liver disease (MAFLD) definition. Several biomarkers show a relationship with MASLD/MAFLD, such as BMI, T2D, HOMA-IR, central obesity, waist circumference, and CKD.

Genetics and Genomics of Pulmonary Fibrosis: Charting the Molecular Landscape and Shaping Precision Medicine.

Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (ILDs), emphasizing the contribution of heritable factors. This state-of-the-art review synthesizes evidence on significant genetic contributors to pulmonary fibrosis (PF), including rare genetic variants and common SNPs. The MUC5B promoter variant is unusual, a common SNP that markedly elevates the risk of early and established PF. We address the utility of genetic variation in enhancing understanding of disease pathogenesis and clinical phenotypes, improving disease definitions, and informing prognosis and treatment response. Critical research gaps are highlighted, particularly the underrepresentation of non-European ancestries in PF genetic studies and the exploration of PF phenotypes beyond usual interstitial pneumonia/IPF. We discuss the role of telomere length, often critically short in PF, and its link to progression and mortality, underscoring the genetic complexity involving telomere biology genes (TERT, TERC) and others like SFTPC and MUC5B. In addition, we address the potential of gene-by-environment interactions to modulate disease manifestation, advocating for precision medicine in PF. Insights from gene expression profiling studies and multiomic analyses highlight the promise for understanding disease pathogenesis and offer new approaches to clinical care, therapeutic drug development, and biomarker discovery. Finally, we discuss the ethical, legal, and social implications of genomic research and therapies in PF, stressing the need for sound practices and informed clinical genetic discussions. Looking forward, we advocate for comprehensive genetic testing panels and polygenic risk scores to improve the management of PF and related ILDs across diverse populations.

How Lifetime Evolution of Parkinson's Disease Could Shape Clinical Trial Design: A Shared Patient-Clinician Viewpoint.

Parkinson's disease (PD) has a long, heterogeneous, pre-diagnostic phase, during which pathology insidiously accumulates. Increasing evidence suggests that environmental and lifestyle factors in early life contribute to disease risk and progression. Thanks to the extensive study of this pre-diagnostic phase, the first prevention trials of PD are being designed. However, the highly heterogenous evolution of the disease across the life course is not yet sufficiently taken into account. This could hamper clinical trial success in the advent of biological disease definitions. In an interdisciplinary patient-clinician study group, we discussed how an approach that incorporates the lifetime evolution of PD may benefit the design of disease-modifying trials by impacting population, target and outcome selection. We argue that the timepoint of exposure to risk and protective factors plays a critical role in PD subtypes, influencing population selection. In addition, recent developments in differential disease mechanisms, aided by biological disease definitions, could impact optimal treatment targets. Finally, multimodal biomarker panels using this lifetime approach will likely be most sensitive as progression markers for more personalized trials. We believe that the lifetime evolution of PD should be considered in the design of clinical trials, and that such initiatives could benefit from more patient-clinician partnerships.

An Updated Review of Management of Resectable Stage III NSCLC in the Era of Neoadjuvant Immunotherapy.

Immune-checkpoint inhibitors (ICIs) have an established role in the treatment of locally advanced and metastatic non-small cell lung cancer (NSCLC). ICIs have now entered the paradigm of early-stage NSCLC. The recent evidence shows that the addition of ICI to neoadjuvant chemotherapy improves the pathological complete response (pCR) rate and survival rate in early-stage resectable NSCLC and is now a standard of care option in this setting. In this regard, stage III NSCLC merits special consideration, as it is heterogenous and requires a multidisciplinary approach to management. As the neoadjuvant approach is being adopted widely, new challenges have emerged and the boundaries for resectability are being re-examined. Consequently, it is ever more important to carefully individualize the treatment strategy for each patient with resectable stage III NSCLC. In this review, we discuss the recent literature in this field with particular focus on evolving definitions of resectability, T4 disease, N2 disease (single and multi-station), and nodal downstaging. We also highlight the controversy around adjuvant treatment in this setting and discuss the selection of patients for adjuvant treatment, options of salvage, and next line treatment in cases of progression on/after neoadjuvant treatment or after R2 resection. We will conclude with a brief discussion of predictive biomarkers, predictive models, ongoing studies, and directions for future research in this space.

Exploring health and disease concepts in healthcare practice: an empirical philosophy of medicine study

In line with recent proposals for experimental philosophy and philosophy of science in practice, we propose that the philosophy of medicine could benefit from incorporating empirical research, just as bioethics has. In this paper, we therefore take first steps towards the development of an empirical philosophy of medicine, that includes investigating practical and moral dimensions. This qualitative study gives insight into the views and experiences of a group of various medical professionals and patient representatives regarding the conceptualization of health and disease concepts in practice and the possible problems that surround them. This includes clinical, epistemological, and ethical issues. We have conducted qualitative interviews with a broad range of participants (n = 17), working in various health-related disciplines, fields and organizations. From the interviews, we highlight several different practical functions of definitions of health and disease. Furthermore, we discuss 5 types of problematic situations that emerged from the interviews and analyze the underlying conceptual issues. By providing theoretical frameworks and conceptual tools, and by suggesting conceptual changes or adaptations, philosophers might be able to help solve some of these problems. This empirical-philosophical study contributes to a more pragmatic way of understanding the relevance of conceptualizing health and disease by connecting the participants’ views and experiences to the theoretical debate. Going back and forth between theory and practice will likely result in a more complex but hopefully also better and more fruitful understanding of health and disease concepts.

Prevalence of dementia among people experiencing homelessness in Ontario, Canada: a population-based comparative analysis

Cognitive decline in people experiencing homelessness is an increasingly recognised issue. We compared the prevalence of dementia among people experiencing homelessness to housed individuals in the general population and those living in low-income neighbourhoods. We conducted a population-based, cross-sectional, comparative analysis using linked health-care administrative data from Ontario, Canada. We included individuals aged 45 years or older on Jan 1, 2019, who visited hospital-based ambulatory care (eg, emergency department), were hospitalised, or visited a community health centre in 2019; and identified people experiencing homelessness if they had one or more health-care records with an indication of homelessness or unstable housing. Prevalence of dementia was ascertained as of Dec 31, 2019, using a validated case definition for Alzheimer's disease and related dementia that was modified to include diagnoses made at a community health centre. Poisson models were used to generate estimates of prevalence. Estimates were compared with Ontarians that accessed any of the same health-care services over the same time, overall (general population group), and among those who were in the lowest quintile of area-based neighbourhood income (low-income group). 12 863 people experiencing homelessness, 475 544 people in the low-income comparator group, and 2 273 068 people in the general population comparator group were included in the study. Dementia prevalence was 68·7 per 1000 population among people experiencing homelessness, 62·6 per 1000 population in the low-income group, and 51·0 per 1000 population in the general population group. Descriptively, prevalence ratios between people experiencing homelessness and the comparator groups were highest within the ages of 55-64 years and 65-74 years in both sexes, ranging from 2·98 to 5·00. After adjusting for age, sex, geographical location of residence (urban vs rural), and health conditions associated with dementia, the prevalence ratio of dementia among people experiencing homelessness was 1·71 (95% CI 1·60-1·82) compared with the low-income group and 1·90 (1·79-2·03) compared with the general population group. People experiencing homelessness experience a high burden of dementia compared with housed populations in Ontario. Findings suggest that people experiencing homelessness might experience dementia at younger ages and could benefit from the development of proactive screening and housing interventions. The Public Health Agency of Canada.

Metabolic dysfunction-associated fatty liver disease: current therapeutic strategies.

The definition of "Metabolic Associated Fatty Liver Disease - MAFLD" has replaced the previous definition of Nonalcoholic Fatty Liver Disease (NAFLD), because cardiometabolic criteria have been added for the prevention of cardiological risk in these patients. This definition leads to an in-depth study of the bidirectional relationships between hepatic steatosis, Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD) and/or their complications. Lifestyle modification, which includes correct nutrition combined with regular physical activity, represents the therapeutic cornerstone of MAFLD. When therapy is required, there is not clear accord on how to proceed in an optimal way with nutraceutical or pharmacological therapy. Numerous studies have attempted to identify nutraceuticals with a significant benefit on metabolic alterations and which contribute to the improvement of hepatic steatosis. Several evidences are supporting the use of silymarin, berberine, curcumin, Nigella sativa, Ascophyllum nodosum, and Fucus vesiculosus, vitamin E, coenzyme Q10 and Omega-3. However, more evidence regarding the long-term efficacy and safety of these compounds are required. There is numerous evidence that highlights the use of therapies such as incretins or the use of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors or other similar therapies which, by assisting existing therapies for pathologies such as diabetes, hypertension, insulin resistance, have given a breakthrough in prevention and the reduction of cardiometabolic risk. This review gave an overview of the current therapeutic strategies that are expected to aid in the treatment and prevention of MAFLD.

Assessing knowledge about hypertension and identifying predictors of inadequate knowledge in Saudi Arabia: A cross-sectional study.

Globally, hypertension is among the leading causes of premature mortality. It is a noncommunicable disease characterized by a persistent state of raised blood pressure that increases the risk of cardiovascular diseases and medical conditions affecting the brain and kidneys. There is a paucity of thorough hypertension knowledge assessment among hypertensive patients in the Jazan region of Saudi Arabia. Thus, this study aimed to assess overall and specific knowledge about hypertension and to identify predictors of inadequate knowledge. A cross-sectional study was conducted in the Jazan region of Saudi Arabia between February and April 2023. Data were collected using an online, self-administered questionnaire divided into two sections. In the first section, the characteristics of the participants were collected. In the second section, the Hypertension Knowledge-Level Scale was used to measure overall and specific knowledge areas (subdimensions). The overall and subdimensional means were tested using Mann-Whitney U and Kruskal-Wallis H tests. Furthermore, the binary logistic regression was conducted to determine inadequate knowledge predictors. In all 253 hypertensive patients were eligible for participation; almost 70% of whom were male. The mean age of the participants was 45 years (±14.7), and their mean overall knowledge score was 17.60 (±5.09), which was equivalent to 67.7% of the maximum score. In addition, 40.7% of participants had an adequate level of hypertension knowledge. The complications subdimension level of knowledge was borderline optimal. At the same time, an adequate knowledge level was detected only in the lifestyle subdimension. Most patients showed inadequate levels of knowledge related to hypertension management. Diet, medical treatment, disease definition, drug compliance, and complications were subsequently the least knowledgeable subdimensions among the study population. Therefore, these subdimensions should be prioritized when planning hypertension educational interventions and during follow-up sessions, especially for patients of younger age groups and those with lower educational levels.

Primary hyperparathyroidism: predictors of sporadic multi-gland disease.

In this review, we discuss the definition, prevalence, and etiology of sporadic multiglandular disease (MGD), with an emphasis on its preoperative and intraoperative predictors. Primary hyperparathyroidism (PHPT) is the third-most common endocrine disorder, and multiglandular parathyroid disease (MGD) is a cause of PHPT. Hereditary MGD can be definitively diagnosed with detailed family history and genetic testing, whereas sporadic MGD presents a greater challenge in clinical practice, and parathyroidectomy for MGD is associated with a higher risk of surgical failure than single gland disease (SGD). Therefore, it is crucial to be able to predict the presence of sporadic MGD in a timely manner, either preoperatively or intraoperatively. Various predictive methods cannot accurately identify all cases of sporadic MGD, but they can greatly optimize the management of MGD diagnosis and treatment and optimize the cure rate. Future research will urge us to investigate more integrative predictive models as well as increase our understanding of MGD pathogenesis.

Prevention of cisplatin-induced hearing loss in children: achievements and challenges for evidence-based implementation of sodium Thiosulfate.

Ototoxicity is a devastating direct, irreversible side effect of platinum use in children with cancer, with its consequent effect on speech, language and social development, quality of life and adult productivity. Cisplatin, an essential chemotherapeutic agent for the treatment of solid tumors in children, is a DNA cross-linking agent. Which causes hearing loss in 50-70% of cisplatin treated children. Fortunately, to prevent hearing loss, sodium thiosulfate (STS), which binds to cisplatin, and reduces the superoxides in both tumor and outer hair cells of the cochlea has now been discovered to be an effective and safe otoprotectant if administered correctly. The aim of this perspective paper is to explore the key safety issues and challenges important for pediatric oncologists and pharmacists when considering the clinical use of STS as an otoprotectant for children and adolescents receiving cisplatin. These include: the choice of the formulation; the timing, both that of the STS in relation to cisplatin as well as the timing of the cisplatin infusion itself; the dosing; the challenge left by the definition of localized versus disseminated disease and the difference in indication for STS, between cisplatin treated patients and those receiving another platinum chemotherapeutic agent, carboplatin.

Prevalence and Factors Associated with Surgical Site Infection in Post Caesarean Mothers

Post-cesarean surgical site infection after cesarean delivery is a surgical problem that significantly contributes to maternal morbidity and mortality. In Uganda, admissions due to surgical site infection following cesarean section have been constant activities of health care facilities, but again, there are limited facts on the factors associated with it, making preventive measures less effective. Therefore, this study aimed to assess the risk factors for post-cesarean section surgical site infection at Fort Portal regional referral hospital, Uganda. A cross-sectional study with a retrospective record review was conducted. The data were analyzed using Statistical Package for Social Science Software (SPSS) version 26. Post-cesarean section surgical site infection was measured based on the disease classification and definition of the term by the Center for Disease Control and Prevention. After checking for the presence and degree of association of factors with outcomes, variables were computed through logistic regression analysis. Factors with a P value <= 0.2 in the bi-variable logistic regression analysis were included in the multivariable logistic regression analysis, and those variables with a P value of <0.05 in the multivariable analysis were considered statistically significant. From the medical records of women who underwent cesarean sections, 77 (12.4%) of them developed surgical site infections. Rural residence [(AOR = 2.30, 95%CI: (1.29, 4.09)], duration of labor greater than 24 hours [(AOR = 3.48, 95%CI: (1.49, 8.09)], rupture of membrane>12 hours [(AOR = 4.61, 95%CI: (2.34, 9.09)], hypertension [(AOR = 3.14, 95%CI: (1.29, 7.59)], and preoperative hemocrit <= 30% [(AAOR = 3.22, 95%CI: (1.25, 8.31)] were factors significantly associated with post-cesarean section surgical site infections. The magnitude of post-cesarean section surgical site infection was a significant problem in Fort Portal regional referral hospital. Minimizing prolonged labor, minimizing early rupture of membranes, properly managing patients with comorbidities like hypertension, strengthening prophylaxis and treatment for anemia during antenatal care, and raising awareness among rural residents can reduce the problem. Zonal policy makers should place emphasis on reducing its burden as well as the provision of qualified health care personnel by the government for better prevention and treatment. Keywords: Cesarean delivery, Post-cesarean, Surgical site infection, Bacteria infection

Persons and their Brains: Life, Death, and Lessened Humanity

Abstract The authors of the articles in this issue of The Journal of Medicine and Philosophy address a wide variety of topics, from definitions of disease to bioenhancement. Each author, however, draws out the importance of careful use of language. Over the years, philosophers of medicine and bioethicists have debated questions such as what qualifies something as a disease, whether disease language is evaluative, whether the term “person” encompasses more than just human beings, and what language ought to be used to best convey complex information to patients. Among a great deal of disagreement on these topics, one thing emerges distinctly: that clarity and careful attention to language is paramount in medicine. The articles in this issue contribute to that conversation, presenting complex arguments and illustrative examples of why it is so important to use clear and well-defined terms in medicine, and of the reality-altering power that our language carries.

Assessing the appropriateness and completeness of ChatGPT-4's AI-generated responses for queries related to diabetic retinopathy.

To evaluate the appropriateness of responses generated by an online chat-based artificial intelligence (AI) model for diabetic retinopathy (DR) related questions. Cross-sectional study. A set of 20 questions framed from the patient's perspective addressing DR-related queries, such as the definition of disease, symptoms, prevention methods, treatment options, diagnostic methods, visual impact, and complications, were formulated for input into ChatGPT-4. Peer-reviewed, literature-based answers were collected from popular search engines for the selected questions and three retinal experts reviewed the responses. An inter-human agreement was analyzed for consensus expert responses and also between experts. The answers generated by the AI model were compared with those provided by the experts. The experts rated the response generated by ChatGPT-4 on a scale of 0-5 for appropriateness and completeness. The answers provided by ChatGPT-4 were appropriate and complete for most of the DR-related questions. The response to questions on the adverse effects of laser photocoagulation therapy and compliance to treatment was not perfectly complete. The average rating given by the three retina expert evaluators was 4.84 for appropriateness and 4.38 for completeness of answers provided by the AI model. This corresponds to an overall 96.8% agreement among the experts for appropriateness and 87.6% for completeness regarding AI-generated answers. ChatGPT-4 exhibits a high level of accuracy in generating appropriate responses for a range of questions in DR. However, there is a need to improvise the model to generate complete answers for certain DR-related topics.

A mobile application for postoperative education of caregivers of children with congenital hypospadias: Requirement analysis.

Hypospadias, a congenital anomaly, can have long-term effects on sexual, urinary, and reproductive functions, making proper postoperative care essential for desirable outcomes, which could be facilitated through a mobile application for diseases with long-term complications. The aim of this study was to investigate the data and functional requirements or minimum data set of a postoperative education mobile application for caregivers of children with hypospadias. A literature review of papers published until April 2023 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was conducted to determine the data and functional requirements of a mobile application that provides postoperative education to caregivers of children with congenital hypospadias. Based on the results, a questionnaire was prepared, and its content validity and reliability were evaluated by CVI and CVR. Additionally, data was examined by 30 residents, specialists, and subspecialists in pediatric surgery using the Delphi approach. The study identified 28 data elements in three main categories: demographic data, clinical data, and application function. Functional requirements of the mobile application were suggested for use in designing the application. Also, the most critical data elements included the definition of disease, the importance of treatment, surgical preparation, bandage, hygiene, symptoms and infection, bleeding, and emergency condition. The study will pave the way for developing postoperative educational applications for caregivers of children with congenital hypospadias. M-Health app developers and clinician specialists can utilize these findings to design practical applications that assist caregivers in managing the care of hypospadias patients.

Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

Universal Fetal Echocardiography for Pregestational Diabetes Mellitus: A Cost-Effectiveness Analysis.

To evaluate the cost effectiveness of universal fetal echocardiogram for patients with pregestational diabetes mellitus by first-trimester hemoglobin A 1c (Hb A 1c ) level. We developed a cost-effectiveness model comparing two strategies of screening for critical fetal congenital heart disease among patients with diabetes: universal fetal echocardiogram and fetal echocardiogram only after abnormal findings on detailed anatomy ultrasonogram. We excluded ventricular septal defect, atrial septal defects, and bicuspid aortic valve from the definition of critical fetal congenital heart disease. Probabilities and costs were derived from the literature. We used individual models to evaluate different scenarios: first-trimester Hb A 1c lower than 6.5%, Hb A 1c 6.5-9.0%, and Hb A 1c higher than 9.0%. Primary outcomes included fetal death, neonatal death, and false-positive and false-negative results. A cost-effectiveness threshold was set at $100,000 per quality-adjusted life-year. Univariable sensitivity analyses were performed to investigate the drivers of the model. Universal fetal echocardiogram is not cost effective except for when first-trimester Hb A 1c level is higher than 9.0% (incremental cost-effectiveness ratio $638,100, $223,693, and $67,697 for Hb A 1c lower than 6.5%, 6.5-9.0%, and higher than 9.0%, respectively). The models are sensitive to changes in the probability of congenital heart disease at a given Hb A 1c level, as well as the cost of neonatal transfer to a higher level of care. Universal fetal echocardiogram became both cost saving and more effective when the probability of congenital heart disease reached 14.48% (15.4 times the baseline risk). In the Monte Carlo simulation, universal fetal echocardiogram is cost effective in 22.7%, 48.6%, and 62.3% of scenarios for each of the three models, respectively. For pregnant patients with first-trimester Hb A 1c levels lower than 6.5%, universal fetal echocardiogram was not cost effective, whereas, for those with first-trimester Hb A 1c levels higher than 9.0%, universal fetal echocardiogram was cost effective. For those with intermediate Hb A 1c levels, universal fetal echocardiogram was cost effective in about 50% of cases; therefore, clinical judgment based on individual patient values, willingness to pay to detect congenital heart disease, and resource availability needs to be considered.