Alternative Causes Research Articles

A retrospective study of autoimmune cerebellar ataxia over a 20-year period in a single institution.

It is important to differentiate autoimmune cerebellar ataxia (ACA) from neurodegenerative CA, but this is sometimes difficult. We performed a retrospective study in a single institution in Japan over a 20-year period to reveal the clinical features of ACA. Patients with CA as the primary neurological symptom were enrolled from those admitted to the Department of Neurology, Hokkaido University Hospital between April 2002 and March 2022. ACA was diagnosed retrospectively according to the following criteria: (1) CA being the predominant symptom; (2) identification of cancer within 2years of onset; (3) improvement in cerebellar symptoms following immunotherapy; and (4) ruling out alternative causes of CA. Patients fulfilling criteria (1), (2), and (4) were classified as paraneoplastic cerebellar degeneration (PCD), while those fulfilling (1), (3), and (4) were classified as non-PCD and enrolled as patients with ACA. Neurodegenerative diseases, e.g., multiple system atrophy (MSA), were confirmed retrospectively based on generally used diagnostic criteria and enrolled. Furthermore, the ACA diagnostic criteria proposed by Dalmau and Graus were applied retrospectively to the ACA patients to examine the validity of the diagnoses. Among the 243 patients with CA, 13 were enrolled as ACA; five were PCD and eight were non-PCD. Eight of these cases met the proposed diagnostic criteria by Dalmau and Graus. MSA was the most prevalent disease among CA patients, with 93 cases. The incidence of cerebellar atrophy was significantly lower in ACA (3/13) than in MSA (92/92). Cerebrospinal fluid (CSF) pleocytosis was significantly more frequent in ACA than in MSA (4/13 vs. 2/55, respectively). However, there was no significant difference in the presence of oligoclonal bands, increased protein in CSF, and laterality differences in ataxia. ACA was present in ~ 5% of Japanese CA patients. The absence of cerebellar atrophy, despite the presence of CA, strongly supports ACA over MSA. While CSF pleocytosis was observed more often in ACA, the positivity rate was only ~ 30%. Since ACA is treatable, further studies are needed to identify additional clinical features and accurate diagnostic biomarkers.

Case Report: Unexplained Mild Hypophosphatemia and Very High Serum FGF23 Concentrations.

Fibroblast growth factor (FGF)23 is one of the major regulators of phosphate homeostasis. Hypophosphatemia can lead to muscle weakness, fatigue, and osteomalacia. In the setting of hypophosphatemia, serum FGF23 can be measured to differentiate between FGF23-mediated and non-FGF23-mediated renal phosphate wasting. C-terminal FGF23 (cFGF23) assays detect both cFGF23 and intact FGF23 (iFGF23). Circulating FGF23 is regulated by 1.25-dihydroxy-vitamin D, parathyroid hormone (PTH), serum phosphate, and serum calcium but also by, for example, iron status, inflammation, erythropoietin, and hypoxia-inducible-factor-1-α. We present the case of a 48-year-old woman with unexplained mild hypophosphatemia, very high cFGF23, and normal iFGF23. The patient proved to have an iron deficiency. Iron deficiency alters the iFGF23-to-cFGF23 ratio. After initiation of iron treatment, cFGF23 strongly decreased. This case report illustrates the limitation of cFGF23 assays and urges clinicians to be aware that cFGF23 concentrations do not necessarily reflect iFGF23 concentrations and that alternative causes for its elevation should be considered (eg, iron deficiency). © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Sex-specific differences in myocardial injury incidence after COVID-19 mRNA-1273 booster vaccination.

To explore the incidence and potential mechanisms of oligosymptomatic myocardial injury following COVID-19 mRNA booster vaccination. Hospital employees scheduled to undergo mRNA-1273 booster vaccination were assessed for mRNA-1273 vaccination-associated myocardial injury, defined as acute dynamic increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration above the sex-specific upper limit of normal on day 3 (48-96 h) after vaccination without evidence of an alternative cause. To explore possible mechanisms, antibodies against interleukin-1 receptor antagonist (IL-1RA), the SARS-CoV-2-nucleoprotein (NP) and -spike (S1) proteins and an array of 14 inflammatory cytokines were quantified. Among 777 participants (median age 37 years, 69.5% women), 40 participants (5.1%; 95% confidence interval [CI] 3.7-7.0%) had elevated hs-cTnT concentration on day 3 and mRNA-1273 vaccine-associated myocardial injury was adjudicated in 22 participants (2.8% [95% CI 1.7-4.3%]). Twenty cases occurred in women (3.7% [95% CI 2.3-5.7%]), two in men (0.8% [95% CI 0.1-3.0%]). Hs-cTnT elevations were mild and only temporary. No patient had electrocardiographic changes, and none developed major adverse cardiac events within 30 days (0% [95% CI 0-0.4%]). In the overall booster cohort, hs-cTnT concentrations (day 3; median 5, interquartile range [IQR] 4-6 ng/L) were significantly higher compared to matched controls (n = 777, median 3 [IQR 3-5] ng/L, p < 0.001). Cases had comparable systemic reactogenicity, concentrations of anti-IL-1RA, anti-NP, anti-S1, and markers quantifying systemic inflammation, but lower concentrations of interferon (IFN)-λ1 (IL-29) and granulocyte-macrophage colony-stimulating factor (GM-CSF) versus persons without vaccine-associated myocardial injury. mRNA-1273 vaccine-associated myocardial injury was more common than previously thought, being mild and transient, and more frequent in women versus men. The possible protective role of IFN-λ1 (IL-29) and GM-CSF warrant further studies.

Update on the Diagnosis and Management of Acute Colonic Pseudo-obstruction (ACPO).

Acute Colonic Pseudo-obstruction (ACPO) is a cause of large intestinal dilation and obstruction without any physical transition point. It remains difficult to diagnose and treat. We review the recent updates on diagnosis and management of ACPO. Recent guidelines have posited that conservative management can be tried in most cases of ACPO, but that early decompression and surgery should be considered. Use of neostigmine is still a viable option but there is also promising data on pyridostigmine as well as prucalopride. Resolution of ACPO should be followed by daily use of polyethylene glycol (PEG) to help prevent recurrence. ACPO warrants early and accurate diagnosis with exclusion of alternate causes of large bowel dilation. Conservative management can be attempted for 48-72h in those with cecal diameters < 12cm and without signs of peritonitis and perforation. Early escalation of management should be attempted with neostigmine followed by endoscopy and/or surgery as needed, given that longer periods of dilation are associated with worse outcomes. There is promising new evidence for use of pyridostigmine and prucalopride, but further trials are needed prior to incorporating them into regular use. Finally, studies are lacking regarding prevention of ACPO after initial resolution.

Incidence, risk factors and outcomes of checkpoint inhibitor-induced liver injury: A 10-year real-world retrospective cohort study

Background & AimsCheckpoint inhibitors (CPI) account for increasing numbers of drug-induced liver injury (DILI) cases. We aimed to determine the incidence rate and risk factors associated with checkpoint inhibitor-induced liver injury (ChILI). MethodsPrescription event monitoring was performed on all melanoma and renal cancer patients who received CPI at a tertiary centre between 2011 and 2021. ChILI cases were identified using the definitions, grading, and causality assessment methods validated for DILI. We assessed risk factors associated with ChILI in CPI-naive patients using multivariable logistic regression model. Consecutive patients with suspected ChILI from two other tertiary centres were adjudicated and combined for case characterisation and outcomes of ChILI. ResultsOut of 432 patients who received CPI over 10 years, ChILI occurred in 38 (8.8%) with an overall incidence rate of 11.5 per 1,000 person-months (95% CI 8.2–15.8). Probability of ChILI was highest in combination therapy (32%) and no new events occurred beyond 135 days of treatment. Risk factor analysis showed that combination therapy, female sex, higher baseline alanine transferase level and lower baseline alkaline phosphatase level were independently associated with higher risk of ChILI. In total, 99 patients were adjudicated to have ChILI from three centres. Although Common Terminology Criteria for Adverse Events classified 20 patients (20.2%) to have ‘life-threatening’ grade 4 hepatitis, ChILI severity was graded as mild in 45 (45.5%) and moderate in the remaining 54 (54.5%) cases. ConclusionsThe real-world risk of ChILI is higher than previously reported. Among patients receiving dual CPI, this risk falls markedly after 4.5 months. As Common Terminology Criteria for Adverse Events overestimates its clinical severity, case-definition, evaluation and management of ChILI should be revised to harmonise care. Impact and implicationsUsing prescription event monitoring over a 10-year period, the incidence rate of checkpoint inhibitor induced liver injury (ChILI) based on established case definitions for drug-induced liver injury (DILI) is 11.5 per 1,000 person-months. Formal causality assessment identified an alternative cause in 19% of patients with suspected ChILI highlighting the importance of systematic evaluation by clinicians to minimise unnecessary immunosuppression. Intensity of monitoring in patients receiving combination therapy regime after 4.5 months of therapy can be reduced as the risk of new onset ChILI beyond this point is minimal. Current Common Terminology Criteria for Adverse Events (CTCAE) grading overestimates clinical severity of ChILI and hence contributes to avoidable hospitalisation.

Approaching Headaches—A Guide to Differential-Diagnostic Considerations and Causal Claims

Headaches can be nociplastic, neuropathic, and nociceptive. Pain related to the latter two categories occurs in the presence of nerve lesions and nociceptive stimuli; attributing pain to the last category requires a list of potential causes and arguments supporting the causal claim. Taking a history and examining patients serves to assess diagnostic criteria and screen for disorders whose diagnosis requires additional examinations. Screening information occurs in two types: one indicates that patients have a headache due to another condition; the other suggests they are at risk. Aspiring to make causal claims for a headache is reasonable because if underlying disorders appear independently and randomly, it is probable that there is only one cause. Thus, having found a cause often implies having found the cause. The prerequisites for causal claims are temporal sequencing, correlation, and elimination of alternate causes. Mechanistic, manipulative, and probabilistic evidence supports the second criterion. The importance of headaches lies in their frequent appearance as an early symptom of an incipient disorder (“sentinel symptom”). Hence, they provide the opportunity to diagnose early diseases with potentially deleterious consequences. Thus, it is sensible to assess each attack carefully and systematically.

A pragmatic clinical trial assessing the effect of a targeted notification and clinical support pathway on the diagnostic evaluation and treatment of individuals with left ventricular hypertrophy (NOTIFY-LVH)

Electronic health records contain vast amounts of cardiovascular data, including potential clues suggesting unrecognized conditions. One important example is the identification of left ventricular hypertrophy (LVH) on echocardiography. If the underlying causes are untreated, individuals are at increased risk of developing clinically significant pathology. As the most common cause of LVH, hypertension accounts for more cardiovascular deaths than any other modifiable risk factor. Contemporary healthcare systems have suboptimal mechanisms for detecting and effectively implementing hypertension treatment before downstream consequences develop. Thus, there is an urgent need to validate alternative intervention strategies for individuals with preexisting-but potentially unrecognized-LVH. Through a randomized pragmatic trial within a large integrated healthcare system, we will study the impact of a centralized clinical support pathway on the diagnosis and treatment of hypertension and other LVH-associated diseases in individuals with echocardiographic evidence of concentric LVH. Approximately 600 individuals who are not treated for hypertension and who do not have a known cardiomyopathy will be randomized. The intervention will be directed by population health coordinators who will notify longitudinal clinicians and offer to assist with the diagnostic evaluation of LVH. Our hypothesis is that an intervention that alerts clinicians to the presence of LVH will increase the detection and treatment of hypertension and the diagnosis of alternative causes of thickened myocardium. The primary outcome is the initiation of an antihypertensive medication. Secondary outcomes include new hypertension diagnoses and new cardiomyopathy diagnoses. The trial began in March 2023 and outcomes will be assessed 12 months from the start of follow-up. The NOTIFY-LVH trial will assess the efficacy of a centralized intervention to improve the detection and treatment of hypertension and LVH-associated diseases. Additionally, it will serve as a proof-of-concept for how to effectively utilize previously collected electronic health data to improve the recognition and management of a broad range of chronic cardiovascular conditions. NCT05713916.

Survey on antiphospholipid syndrome diagnosis and antithrombotic treatment in patients with ischemic stroke, other brain ischemic injury, or arterial thromboembolism in other sites: communication from ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

BackgroundThe optimal strategy for diagnosis and antithrombotic treatment of patients with antiphospholipid syndrome (APS)–associated acute ischemic stroke (AIS), transient ischemic attack (TIA), or other brain ischemic injury is poorly defined. ObjectivesThe survey goal was to capture variations in diagnosis and antithrombotic treatment of APS-associated ischemic stroke and related disorders to inform guidance and clinical trials to define optimal management. MethodsProfessional colleagues, including key opinion leaders, were invited to complete a REDCap survey questionnaire initiated by the International Society on Thrombosis and Haemostasis Scientific and Standardisation Committee Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. The survey data were tallied using simple descriptive statistics. ResultsThere was generally good agreement on several aspects, including which patients to test for antiphospholipid antibodies (aPL), use of a lifelong vitamin K antagonist for AIS or recurrent TIA, and formal cognitive assessment for suspected cognitive impairment. There was less agreement on other aspects, including aPL testing for brain ischemic injury other than AIS/TIA or if an alternative cause for AIS or TIA exists; choice of aPL tests, their timing, and age cutoff; the aPL phenotype to trigger antithrombotic treatment; management for patent foramen ovale; antithrombotic treatment for first TIA or white matter hyperintensities; head magnetic resonance imaging specifications; and low-molecular-weight heparin dosing/anti-Xa monitoring in pregnancy. The survey highlighted that approximately 25% practice at dedicated APS clinics and <50% have a multidisciplinary team structure for patients with APS. ConclusionMuch of the variation in practice reflects the lack of evidence-based recommendations. The survey results should inform the development of a more uniform multidisciplinary consensus approach to diagnosis and antithrombotic treatment.

D-dimer as a diagnostic and prognostic plasma biomarker in patients with a first episode of acute pericarditis

ObjectivesThe impact of plasma biomarkers on diagnosis and prognosis of patients with acute pericarditis (AP) has been poorly investigated. This study aims to assess the diagnostic and prognostic role of d-dimer (DD), an easily obtainable biomarker, in patients with AP. Patients and methodsThis is a prospective clinical study enrolling 265 consecutive patients hospitalized between September 2010 and May 2019 with a first episode of AP. At baseline, demographics, clinical features, laboratory and imaging findings were recorded. All patients were followed-up for a minimum of 18 months. Endpoints included cardiac tamponade, new-onset atrial fibrillation, pericardial drainage, recurrent/constrictive pericarditis and death. ResultsDD was measured in 165 out of 265 patients (62.3%, median levels 1456 ng/mL) Among them, 121 patients (73.3%) presented with elevated age-adjusted DD levels. Patients with elevated DD depicted a higher rate of pleural (69.4%, vs 38.6%, p<0.001) and pericardial effusions (89.3% vs 72.7%, p = 0.009). Elevated DD correlated with admission (rho=0.37) and peak (rho=0.36) C-reactive protein values. Patients with elevated DD depicted a trend towards a greater prevalence of pericardial tamponade vs those without (14.9% vs 4.5% respectively, p = 0.07). In the 43.8% of patients with elevated DD who underwent computed tomography pulmonary angiography (CTPA), no case of pulmonary embolism or aortic syndrome was unveiled. ConclusionDD elevation is detected in the majority of AP cases at presentation and may herald cardiac tamponade. In patients with chest pain not attributable to alternative causes, elevated DD denotes an inflammatory condition and should not prompt unnecessary investigations, such as CTPA.

Retinodural haemorrhage of infancy, abusive head trauma, shaken baby syndrome: The continuing quest for evidence.

The shaken baby syndrome was originally proposed in the 1970s without any formal scientific basis. Once data generated by scientific research was available, the hypothesis became controversial. There developed essentially two sides in the debate. One side claimed that the clinical triad of subdural haemorrhage, retinal haemorrhage, and encephalopathy, or its components, is evidence that an infant has been shaken. The other side stated this is not a scientifically valid proposal and that alternative causes, such as low falls and natural diseases, should be considered. The controversy continues, but the contours have shifted. During the last 15 years, research has shown that the triad is not sufficient to infer shaking or abuse and the shaking hypothesis does not meet the standards of evidence-based medicine. This raises the issue of whether it is fit for either clinical practice or for the courtroom; evidence presented to the courts must be unassailable. WHAT THIS PAPER ADDS: There is insufficient scientific evidence to assume that an infant with the triad of subdural haemorrhage (SDH), retinal haemorrhage, and encephalopathy must have been shaken. Biomechanical and animal studies have failed to support the hypothesis that shaking can cause SDH and retinal haemorrhage. Patterns of retinal haemorrhage cannot distinguish abuse. Retinal haemorrhages are commonly associated with extracerebral fluid collections (including SDH) but not with shaking. Infants can develop SDH, retinal haemorrhage, and encephalopathy from natural diseases and falls as low as 1 foot. The shaking hypothesis and the literature on which it depends do not meet the standards of evidence-based medicine.

Market Reaction to Modified Audit Opinions: A Systematic Literature Review in Both Developed and Developing Countries

The purpose of this paper is to review the empirical literature on value relevance of audit reports by providing current evidence on the market reaction to modified audit opinions (MAOs). This study is motivated by the argument that recent research has resolved the research designs problems raised by the pre-2010 studies that resulted in unmitigated and contradictory results. We adopt a systematic literature review based on the guidelines presented by Kitchenham et al. to review papers published between 2010 and 2020. The main findings of our review show sufficient evidence that MAOs are indeed useful to investors in making decisions in developed countries, which is evidenced by the fact that the MAOs have a negative effect on the share prices of companies. In contrast, evidence from studies conducted in developing countries shows null market reaction to MAOs, with the exception of the Chinese market, which shows a significant reaction. The methodological limitations and alternative causes behind the null market reaction to MAOs of studies conducted in developing countries are discussed in this paper.

Management of Patients With Patent Foramen Ovale and Stroke: A National Survey of Interventional Cardiologists and Vascular Neurologists.

Background Results from multiple clinical trials support patent foramen ovale closure after cryptogenic stroke in select patients, but it remains unclear how new data and updated professional society guidelines have impacted clinical practice. Here, we aimed to compare how stroke neurologists and interventional cardiologists approach patients with cryptogenic stroke with patent foramen ovale and how critical anatomic and clinical factors influence decision making. Methods and Results An electronic survey was administered to 1556 vascular neurologists and 1057 interventional cardiologists throughout the United States. The survey addressed factors such as patient age, preclosure workup, and postclosure antithrombotics. Clinical vignettes highlighted critical variables and used a 5-point Likert scale to assess the providers' level of support for closure. There were 491 survey responses received from 301 (of 1556) vascular neurologists and 190 (of 1057) interventional cardiologists, with an overall response rate of 19%. Vascular neurologists were more likely to recommend against closure on the basis of older age (P<0.001). Interventional cardiologists are more supportive of closure across a range of clinical vignettes, including a very carefully selected patient with cryptogenic stroke (P<0.001), a patient with a high-risk alternative stroke cause (P<0.001), and a range of cases highlighting clinical variables where data are lacking. The majority of interventionalists (88%) seek neurology consultation before pursuing patent foramen ovale closure. Conclusions lnterventional cardiologists are more likely than vascular neurologists to support patent foramen ovale closure across a range of situations. This emphasizes the importance of collaboration and shared decision making, but also reveals an opportunity for professional society educational outreach.

Multidisciplinary approach to inherited causes of dual sensory impairment.

This article presents a review of the main causes of inherited dual sensory impairment (DSI) with an emphasis on the multidisciplinary approach. A narrative review of English literature published before January 2023 was conducted using PubMed, Medline, and Scopus databases. The different causes of inherited DSI are discussed from a multidisciplinary perspective. There are a wide range of dual sensory impairment (DSI), commonly referred to as blindness and deafness. While Usher syndrome is the most frequent genetic cause, other genetic syndromes such as Alport syndrome or Stickler syndrome can also lead to DSI. Various retinal phenotypes, including pigmentary retinopathy as seen in Usher syndrome, vitreoretinopathy as in Stickler syndrome, and macular dystrophy as in Alport syndrome, along with type of hearing loss (sensorineural or conductive) and additional systemic symptoms can aid in diagnostic suspicion. A thorough ophthalmologic and otorhinolaryngologic examination can help guide diagnosis, which can then be confirmed with genetic studies, crucial for determining prognosis. Effective hearing rehabilitation measures, such as hearing implants, and visual rehabilitation measures, such as low vision optical devices, are crucial for maintaining social interaction and proper development in these patients. While Usher syndrome is the primary cause of inherited dual sensory impairment (DSI), other genetic syndromes can also lead to this condition. A proper diagnostic approach based on retinal phenotypes and types of hearing loss can aid in ruling out alternative causes. Multidisciplinary approaches can assist in reaching a definitive diagnosis, which has significant prognostic implications.

1363-P: Clinical Profile and Outcome of Diabetic Ketoacidosis in an Emergency Department Non-COVID ICU

The clinical profile of DKA in a 4-bedded ED ICU of a single tertiary care centre from 12 April 2022 to 4 January 2023 is presented. A total of 11 DKA events were managed, with a mean age of 45.5 ± 19.2 y with M: F ratio of 1:2.7. Type 1 in 36%, type 2 in 45% and 18% were unclassified. 55% had no comorbidities, and 45% had Hypertension, CAD, CKD, and hypothyroidism. Presented with nausea &amp; vomiting in 6 (55 %), shortness of breath in 5 (45%), dysuria in 4 (36 %), fever &amp; fatiguability in 3 (27%), abdominal pain, chest pain, loose stools in 2 (18%), cough, haematemesis and loss of consciousness in 1 (9%). Of the total patients, 36 % were only on OADs, 18 % on Insulin and OADs and 18 % on Insulin alone. Duration of diabetes ranged from 2 to 13 years, and 2 were first diagnosed. Reasons for DKA were Non-adherence to medication (18%), the first presentation of DM (18%), Infections (73%), CAD-ACS (18%) and Pancreatitis (9%). One patient was on Dapagliflozin 10 mg daily with blood glucose 240 mg/dL at presentation. Lab parameters are shown in Table 1. Course in ICU: All patients received the standard treatment of DKA. 27 % had AKI and 27% had Acute on CKD. ICU mortality was 36 % with definite alternative causes identified for death. Conclusions: Infections are the most important cause of precipitating events for DKA. Co-morbidities and Complications decide the outcome and early recognition and standard treatment and ICU care are important in critically ill. Disclosure C.R: None. B.N.Jami: None. A.Suresh: None. A.J.Mangaly: None.

Transjugular intrahepatic portosystemic shunt-induced hemolysis in a non-cirrhotic patient: a case report

BackgroundIn the 1990s, transjugular intrahepatic portosystemic shunts (TIPS) were performed using bare metal stents, and stent-induced hemolysis was a complication noted in 10% of patients. This was due to the mechanical stress created by turbulent flow from the uncovered interstices. Polytetrafluoroethylene (PTFE) stents came into regular use in the early 2000s becoming the standard equipment for TIPS placements, which are predominately covered. Due to this, stent-induced hemolysis has become a rare phenomenon.Case presentationWe describe a case of TIPS-induced hemolysis in a 53-years-old Caucasian female patient without cirrhosis. The patient had a history of heterozygous factor 5 Leiden mutation and abnormal lupus anticoagulant profile with development of a portal vein thrombus. She had undergone previous TIPS placement complicated by a TIPS thrombosis 3 years after initial placement requiring venoplasty and extension of the stent. Within one month, the patient developed hemolytic anemia with extensive evaluation that did not yield an alternative cause. Due to temporal association and clinical symptoms, the hemolytic anemia was attributed to the recent TIPS revision.ConclusionThis particular case of TIPS-induced hemolysis in a patient who does not have cirrhosis has not been previously described in the literature. Our case highlights that TIPS-induced hemolysis should be considered in anyone who could have potential underlying red blood cell dysfunction, not just those with cirrhosis. Further, the case demonstrates an important point that mild hemolysis (i.e., not requiring blood transfusion) can likely be managed conservatively, without stent removal.

Use of a Ketogenic Diet in the Successful Management of a Dog With Refractory Epilepsy

Epilepsy is one of the most common neurological conditions seen in dogs. Idiopathic or primary epilepsy is diagnosed whenever an alternate structural, inflammatory, or metabolic cause cannot be confirmed. About 30% of dogs with idiopathic epilepsy will become refractory to standard treatments and still sustain a considerable incidence of seizures. Dietary changes have been investigated as aids in the treatment of seizures; however, using a ketogenic diet as a means of metabolic therapy has been minimally investigated in dogs. This report describes the successful use of a ketogenic diet in the management of epilepsy in a dog.

Developing an Artificial Intelligence-Guided Signal Detection in the Food and Drug Administration Adverse Event Reporting System (FAERS): A Proof-of-Concept Study Using Galcanezumab and Simulated Data.

Time- and resource-demanding activities related to processing individual case safety reports (ICSRs) include manual procedures to evaluate individual causality with the final goal of dismissing false-positive safety signals. Eminent experts and a representative from pharmaceutical industries and regulatory agencies have highlighted the need to automatize time- and resource-demanding procedures in signal detection and validation. However, to date there is a sparse availability of automatized tools for such purposes. ICSRs recorded in spontaneous reporting databases have been and continue to be the cornerstone and the most important data source in signal detection. Despite the richness of this data source, the incessantly increased amount of ICSRs recorded in spontaneous reporting databases has generated problems in signal detection and validation due to the increase in resources and time needed to process cases. This study aimed to develop a new artificial intelligence (AI)-based framework to automate resource- and time-consuming steps of signal detection and signal validation, such as (1) the selection of control groups in disproportionality analyses and (2) the identification of co-reported drugs serving as alternative causes, to look to dismiss false-positive disproportionality signals and therefore reduce the burden of case-by-case validation. The Summary of Product Characteristics (SmPC) and the Anatomical Therapeutic Chemical (ATC) classification system were used to automatically identify control groups within and outside the chemical subgroup of the proof-of-concept drug under investigation, galcanezumab. Machine learning, specifically conditional inference trees, has been used to identify alternative causes in disproportionality signals. By using conditional inference trees, the framework was able to dismiss 20.00% of erenumab, 14.29% of topiramate, and 13.33% of amitriptyline disproportionality signals on the basis of purely alternative causes identified in cases. Furthermore, of the disproportionality signals that could not be dismissed purely on the basis of the alternative causes identified, we estimated a 15.32%, 25.39%, and 26.41% reduction in the number of galcanezumab cases to undergo manual validation in comparison with erenumab, topiramate, and amitriptyline, respectively. AI could significantly ease some of the most time-consuming and labor-intensive steps of signal detection and validation. The AI-based approach showed promising results, however, future work is needed to validate the framework.

Cause typicality and the continued influence effect.

A large body of research has focused on whether and how readers update their knowledge of events when an initial piece of causal information is corrected. These studies have indicated that corrections can reduce, but do not eliminate, readers' reliance on the initial cause when drawing inferences or making decisions about the events (i.e., the continued influence effect). Additional studies suggest that supplementing a correction with an alternative cause can further reduce reliance on discredited initial causes. In three experiments, we interrogated the importance of cause typicality for the generalizable utility of these correction strategies by manipulating the typicality of initial and alternative causes. We found evidence that participants showed greater reliance on a typical than an atypical initial cause both before and after correction, but no consistent evidence that this typicality impacted the effectiveness of the correction. Furthermore, the typicality of the alternative causes used to supplement a correction did not seem to matter with respect to updating. These results highlight the importance that characteristics of an initial cause can have for event encodings and corrections, identifying critical boundary conditions for understanding the effects of corrections on knowledge revision and the continued influence effect. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Being Negative for SARS-COV-2 after four Weeks of Coughing Requires Considerations of Alternative Causes.

Being Negative for SARS-COV-2 after four Weeks of Coughing Requires Considerations of Alternative Causes.

Prevalence and Risk Factors of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study at a Tertiary Care Center

Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is an emerging concern among patients with Type 2 Diabetes Mellitus (DM). This study was designed to evaluate the prevalence of NAFLD in Type 2 DM patients and to identify associated factors that may contribute to its occurrence. Methodology: Conducted in a tertiary care center's general medicine department from May 2020 to June 2021, this cross-sectional study enrolled 400 type-II diabetic patients, aged 35 years and above. Comprehensive interviews were performed to determine disease duration and medication usage and to exclude alternative causes of NAFLD. Physical examinations, including measurements of BMI and waist-hip circumference, along with abdominal ultrasonography, were utilized to detect and grade fatty liver. Results: The sample consisted of 217 females (59.8%) and 146 males (40.2%), with 67.2% having a diabetes diagnosis for over 10 years. NAFLD was identified in 69.1% of patients, more frequently in females (69%). A significant relationship was established between NAFLD occurrence and the duration of DM, BMI, and waist-hip ratio (p &lt; 0.05). Conclusion: NAFLD was found in a striking majority of the diabetic population studied, approximately 70%, with a higher prevalence in females. Factors significantly linked to NAFLD incidence included the duration of diabetes and elevated measures of obesity and waist circumference. These findings underscore the need for heightened awareness and targeted interventions for this patient population. Keywords: Non-Alcoholic Fatty Liver Disease (NAFLD), Type-II Diabetes Mellitus (DM), prevalence, risk factors.