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Prevalence and classification of congenital thoracic vertebral body abnormalities in neurologically normal brachycephalic ‘screw-tail’ dog breeds in referral practice in Australia

Aust Vet J. 2024 Jul 20. doi: 10.1111/avj.13361. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the prevalence, type, site and breed predisposition of thoracic congenital vertebral malformations (CVM) in neurologically normal brachycephalic ‘screw-tail’ dog breeds.

STUDY DESIGN: Retrospective case series.

ANIMALS: Neurologically normal French Bulldogs (n = 63), British Bulldogs (n = 42), Boston Terriers (n = 4) and Pugs (n = 86) presenting for brachycephalic obstructive airway syndrome treatment.

METHODS: Either a plain computer tomography scan of the thorax or lateral and dorso-ventral digital radiographs of the thoracic vertebral column of each dog were assessed for any vertebral malformations and classed according to the Modified McMaster vertebral abnormality classification scheme proposed by Guiterrez et al. RESULTS: The prevalence of dogs with one or more abnormal vertebrae was 96.82% in French Bulldogs, 90.47% in British Bulldogs, and 76.74% in Pugs. Pugs had significantly lower instances of CVMs than French Bulldogs. The four Boston Terriers all had vertebral malformations, but the results were not considered to be statistically significant due to their small sample size. In French Bulldogs and British Bulldogs, ventral hypoplasia (Type 3) occurred at greater rates than all other types, followed by ventral and median hypoplasia (Types 7) and symmetrical hypoplasia (Type 8). In Pugs, symmetrical hypoplasia (Type 8) was the most common and then ventral hypoplasia (Type 3). The most affected vertebrae were T6-T9 in Pugs and T5-T10 in French Bulldogs and British Bulldogs.

CONCLUSIONS: The majority of neurologically normal brachycephalic ‘screw-tail’ dogs assessed in this paper possessed one or more congenital thoracic vertebral malformations. Dogs with vertebral malformations were found to be more likely to have more than one affected vertebra. Sex had no effect on the prevalence of CVM.

CLINICAL RELEVANCE: A substantial number of neurologically normal brachycephalic ‘screw-tail’ dogs suffer from congenital vertebral malformations. Thus, the need for selective breeding programmes to eliminate this hereditary condition is crucial.

PMID:39032038 | DOI:10.1111/avj.13361

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Performance evaluation of predictive models for detecting MMR gene mutations associated with Lynch syndrome in cancer patients in a Chinese cohort in Taiwan

Int J Cancer. 2024 Jul 20. doi: 10.1002/ijc.35106. Online ahead of print.

ABSTRACT

Identifying Lynch syndrome significantly impacts cancer risk management, treatment, and prognosis. Validation of mutation risk predictive models for mismatch repair (MMR) genes is crucial for guiding genetic counseling and testing, particularly in the understudied Asian population. We evaluated the performance of four MMR mutation risk predictive models in a Chinese cohort of 604 patients with colorectal cancer (CRC), endometrial cancer (EC), or ovarian cancer (OC) in Taiwan. All patients underwent germline genetic testing and 36 (6.0%) carried a mutation in the MMR genes (MLH1, MSH2, MSH6, and PMS2). All models demonstrated good performance, with area under the receiver operating characteristic curves comparable to Western cohorts: PREMM5 0.80 (95% confidence interval [CI], 0.73-0.88), MMRPro 0.88 (95% CI, 0.82-0.94), MMRPredict 0.82 (95% CI, 0.74-0.90), and Myriad 0.76 (95% CI, 0.67-0.84). Notably, MMRPro exhibited exceptional performance across all subgroups regardless of family history (FH+ 0.88, FH- 0.83), cancer type (CRC 0.84, EC 0.85, OC 1.00), or sex (male 0.83, female 0.90). PREMM5 and MMRPredict had good accuracy in the FH+ subgroup (0.85 and 0.82, respectively) and in CRC patients (0.76 and 0.82, respectively). Using the ratio of observed and predicted mutation rates, MMRPro and PREMM5 had good overall fit, while MMRPredict and Myriad overestimated mutation rates. Risk threshold settings in different models led to different positive predictive values. We suggest a lower threshold (5%) for recommending genetic testing when using MMRPro, and a higher threshold (20%) when using PREMM5 and MMRPredict. Our findings have important implications for personalized mutation risk assessment and counseling on genetic testing.

PMID:39032036 | DOI:10.1002/ijc.35106

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Response and outcome of patients with melanoma skin metastases and immune checkpoint inhibition

Int J Cancer. 2024 Jul 20. doi: 10.1002/ijc.35103. Online ahead of print.

ABSTRACT

It is known, that different metastatic organ systems respond differently to immune checkpoint inhibitors (ICIs). In this study, we aimed to investigate the extent to which skin/subcutaneous metastases respond to ICI or targeted therapies (TTs) and whether the response rate differs from that of distant metastases in the same patient. Patients with melanoma diagnosed between January 2021 and September 2023 with at least one skin/subcutaneous metastasis who had received therapy with ICI or TT in an advanced setting were included in the analysis. Best overall response (BOR) was classified according to the revised response evaluation criteria in solid tumors (RECIST). The BOR of skin metastases and visceral metastases to ICI and TT was compared using the chi-square test. Skin metastases treated with ICI a first-line setting showed an overall response rate (ORR) of 44.1%. In contrast, visceral metastases had a higher ORR of 51.1%. However, the difference was not statistically significant (p = .77). Regarding TT, the ORR for skin metastases was 57.1%, compared to 38.5% for visceral metastases (p = .59). Interestingly, the ORR for skin/subcutaneous metastases was notably lower with ICI compared to visceral metastases, in contrast to patients who underwent TT. Skin metastases showed a poorer response to ICI than visceral metastases. Therefore, careful monitoring is recommended to detect non-response early in patients with skin metastases as skin metastases may have a worse response than TT. A larger cohort is needed for a comprehensive analysis and confirmation of our results.

PMID:39032035 | DOI:10.1002/ijc.35103

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Clinical Significance of IgG4 Serum Concentration in Graves’ Disease

Arch Immunol Ther Exp (Warsz). 2024 Jul 20;72(1). doi: 10.2478/aite-2024-0015. eCollection 2024 Jan 1.

ABSTRACT

Elevated immunoglobulin G4 (IgG4) serum antibodies are an important feature of IgG4-related disease. However, IgG4 antibodies can play a role in autoimmune thyroid disorders. In this study, we aimed to evaluate the impact of serum IgG4 levels on clinical features of Graves’ disease (GD). We recruited 60 patients with GD (48 patients without thyroid eye disease, 12 patients with moderate-to-severe Graves’ orbitopathy [GO], and 25 healthy control subjects). The prevalence of high IgG4 serum concentration was 4.2% among GD patients without GO and 33.33% in patients with moderate-to-severe GO. The group with GO had significantly higher median IgG4 levels (87.9 mg/dL) than the control group (41.2 mg/dL, P = 0.034) and the GD without GO group (30.75 mg/dL, P < 0.001). Patients with thyroid nodules had lower IgG4 levels than patients without thyroid nodules, but the difference was not statistically significant (35.7 [24.8; 41.53] mg/dL vs. 43 [30.1; 92.7] mg/dL, P = 0.064). IgG4 as a diagnostic tool for moderate-to-severe GO had the following parameters: area under the curve (AUC): 0.851 (P < 0.001), at the cut-off value of 49 mg/dL, negative predictive value: 100%, positive predictive value: 48%, sensitivity: 100%, specificity: 73%. There were no significant differences between the high and normal IgG4 groups in thyroid hormones, antithyroid antibodies, and ultrasound features. Serum IgG4 levels are associated with some of the clinical features of GD and can help in the diagnostic process of the disease. More research is needed to better understand the pathophysiology of IgG4 involvement in GD.

PMID:39032009 | DOI:10.2478/aite-2024-0015

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A clinical application for arterial coupling and histomorphometric comparison of internal mammary and thoracodorsal arteries for safe use

Microsurgery. 2024 Sep;44(6):e31214. doi: 10.1002/micr.31214.

ABSTRACT

BACKGROUND: In breast reconstruction, arterial coupling has been reported to be more favorable in the thoracodorsal artery (TDA) than the internal mammary artery (IMA). This technique may help overcome anastomosis in a small, deep space. Understanding the arteries’ mechanical properties is crucial for breast reconstruction’s safety and success.

METHODS: Abdominal-based free flap breast reconstructions performed by a single surgeon between 2020 and 2022 were retrospectively analyzed. The patients were classified by microanastomosis technique (handsewn and coupler device) to compare the rate of vascular revision. Histomorphometric analysis of arterial coupling in TDA and IMA was performed in 10 fresh cadavers for comparing wall thickness and composition, including densities of elastic fiber, smooth muscle, and collagen.

RESULTS: A total of 309 patients (339 reconstructed breasts) were included. There were 29 patients in the TDA handsewn group (A), 38 patients in the TDA coupler group (B), and 242 patients in the IMA handsewn group (C). The rates of arterial revision in groups A, B, and C were 0.00% (95%CI: 0.00%-11.03%), 2.5% (95%CI: 0.44%-12.88%), and 1.49% (95%CI: 0.58%-3.77%), respectively, with no statistically significant differences (p-value = .694). Histologically, the thickness of the tunica media and adventitia between IMA and TDA showed no significant difference. The density of elastic fiber was significantly higher in IMA (16.70%) than in TDA (0.79%) (p-value <.001).

CONCLUSION: The histologic characteristics of TDA are more favorable for arterial coupling than those of IMA. Arterial coupling is a safe option in situations where TDA anastomosis must be performed through a narrow and deep incision.

PMID:39031998 | DOI:10.1002/micr.31214

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EVALPAX: Evaluation of a pharmacist-driven protocol for nirmatrelvir/ritonavir prescribing in a community hospital system

Am J Health Syst Pharm. 2024 Jul 20:zxae211. doi: 10.1093/ajhp/zxae211. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: The purpose of this study was to evaluate pharmacist prescribing of nirmatrelvir/ritonavir to ensure this method of increasing access to treatment is safe and effective.

METHODS: This multicenter, retrospective observational study included patients receiving a prescription for nirmatrelvir/ritonavir by a physician, nurse practitioner (NP), physician assistant (PA), or pharmacist at an Indiana University (IU) Health West Central Region site over a 3-month period. Patients were divided into two groups: those who received nirmatrelvir/ritonavir prescribed by a pharmacist (the pharmacist prescribed group) and those who received nirmatrelvir/ritonavir prescribed by other providers (the physician/NP/PA prescribed group). Electronic health record (EHR) reviews were performed to assess the appropriateness of prescriptions based on the presence of risk factors and symptoms, day of symptom onset, and dosing. The primary endpoint was the overall appropriateness of nirmatrelvir/ritonavir prescriptions in the two study groups based on emergency use authorization inclusion and exclusion requirements. Secondary endpoints included appropriateness of nirmatrelvir/ritonavir dosing and medically attended visits or mortality within 30 days. Statistical analysis of the endpoints occurred post hoc utilizing the Fisher’s exact test.

RESULTS: A total of 259 patients were included in the pharmacist prescribed group and 265 patients in the physician/NP/PA prescribed group. Overall appropriate nirmatrelvir/ritonavir prescribing occurred in 258 patients (99.6%) and 232 patients (87.5%) in the pharmacist and physician/NP/PA prescribed groups, respectively (P < 0.0001). Nirmatrelvir/ritonavir dosing was appropriate in 256 patients (98.8%) and 240 patients (90.6%) in the pharmacist and physician/NP/PA prescribed groups, respectively (P < 0.0001). The 30-day rates of medically attended visits were similar between groups. No patients died within 30 days of treatment in either group.

CONCLUSION: Pharmacist prescribing of nirmatrelvir/ritonavir may result in a higher likelihood of prescriptions meeting overall appropriateness criteria. Pharmacists represent an important healthcare professional resource to improve nirmatrelvir/ritonavir prescribing and utilization.

PMID:39030731 | DOI:10.1093/ajhp/zxae211

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Further Psychometric Evaluation of the Eight-Item Hospice Philosophy Scale: Results From a National Sample of Interdisciplinary Hospice Clinicians

J Appl Gerontol. 2024 Jul 20:7334648241265183. doi: 10.1177/07334648241265183. Online ahead of print.

ABSTRACT

This study examined the psychometric properties of the eight-item Hospice Philosophy Scale (HPS-8) through confirmatory factor analysis; differential item functioning by age, gender, race, and professional discipline; and internal consistency reliability. We administered the HPS-8 to a national convenience sample of 471 interdisciplinary hospice clinicians. Confirmatory factor analysis results supported a one-factor model with an error correlation between two similarly worded items, χ2(19) = 48.38, p < .001 (RMSEA = .06, SRMR = .03, CFI = .98, TLI = .97). “Multiple indicators, multiple causes” model results indicated differential item functioning by age, race, and/or professional discipline on five items. However, subsequent uncorrected and differential item functioning-corrected models detected no statistically significant HPS-8 mean differences by grouping variables. Composite reliability results (CR = .82) demonstrated acceptable internal consistency reliability. Our results support the HPS-8 as a valid and reliable measure of attitudes toward the hospice philosophy of care in hospice clinicians.

PMID:39030730 | DOI:10.1177/07334648241265183

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Prevalence and predictors of problematic tinnitus

Int J Audiol. 2024 Jul 20:1-7. doi: 10.1080/14992027.2024.2378804. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the prevalence and characteristics of problematic tinnitus in a representative United States (US) sample.

DESIGN: Cross-sectional study of the NHANES database from 2011-2012 and 2015-2016.

STUDY SAMPLE: 8029 records were included for analysis.

RESULTS: The prevalence of any tinnitus was 16.32%. Only 1.38% reported tinnitus as a big problem or worse. Univariate analysis revealed a statistically significant relationship between tinnitus constancy and duration with severity, where more constant perception and longer duration was related to increased severity (p < 0.0001). Multivariable models showed a clear relationship of increased odds ratio (OR) of problematic tinnitus with constancy of tinnitus but not duration. Furthermore, multivariable models showed higher Body Mass Index (OR= 1.013, 95% CI: 0.99-1.03), sleep trouble (OR = 2.016, 95% CI: 1.52-2.66) and comorbidities (OR = 1.43, 95%CI: 1.06-1.94) were all associated with increased problematic tinnitus, but not non-problematic tinnitus.

CONCLUSIONS: Our study demonstrated that the prevalence of problematic tinnitus is much lower than the prevalence of any tinnitus. There was also a relationship between BMI, sleep trouble, other comorbidities and increased odds of problematic tinnitus. Tinnitus severity was significantly related to constancy of perception but had a less clear relationship to duration.

PMID:39030727 | DOI:10.1080/14992027.2024.2378804

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The role of prescription opioid and cannabis supply policies on opioid overdose deaths

Am J Epidemiol. 2024 Jul 18:kwae210. doi: 10.1093/aje/kwae210. Online ahead of print.

ABSTRACT

Mandatory prescription drug monitoring programs and cannabis legalization have been hypothesized to reduce overdose deaths. We examined associations between prescription monitoring programs with access mandates (“must-query PDMPs”), legalization of medical and recreational cannabis supply, and opioid overdose deaths in United States counties in 2013-2020. Using data on overdose deaths from the National Vital Statistics System, we fit Bayesian spatiotemporal models to estimate risk differences and 95% credible intervals (CrI) in county-level opioid overdose deaths associated with enactment of these state policies. Must-query PDMPs were independently associated with on average 0.8 (95% CrI: 0.5, 1.0) additional opioid-involved overdose deaths per 100,000 person-years. Legal cannabis supply was not independently associated with opioid overdose deaths in this time period. Must-query PDMPs enacted in the presence of legal (medical or recreational) cannabis supply were associated with 0.7 (95% CrI: 0.4, 0.9) more opioid-involved deaths, relative to must-query PDMPs without any legal cannabis supply. In a time when overdoses are driven mostly by non-prescribed opioids, stricter opioid prescribing policies and more expansive cannabis legalization were not associated with reduced overdose death rates.

PMID:39030721 | DOI:10.1093/aje/kwae210

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Global and regional mortality statistics of nipah virus from 1994 to 2023: a comprehensive systematic review and meta-analysis

Pathog Glob Health. 2024 Jul 20:1-10. doi: 10.1080/20477724.2024.2380131. Online ahead of print.

ABSTRACT

The mortality rate of Nipah virus (NiV) can vary in different regions, and its pattern across timelines has yet to be assessed. The primary objective is to perform a comparative analysis of mortality rates across different timelines and countries. Articles reporting NiV mortality from inception to November 2023 were analyzed in PubMed, Ovid Embase, Scopus, and Web of Science databases. A meta-analysis utilizing random-effects models determined the mortality rate secondary to NiV complications. The initial search strategy yielded 1213 records, of which 36 articles met the inclusion criteria, comprising 2736 NiV patients. The Global mortality rate of the Nipah virus in the 2014-2023 decade was 80.1% (CI: 68.7-88.1%), indicating a significant 24% increase compared to the preceding decade (2004-2013) with a mortality rate of 54.1% (CI: 35.5-71.6%). Among the countries analyzed for overall mortality from 1994-2023, India experienced the highest mortality rate at 82.7% (CI: 74.6-88.6%), followed by Bangladesh at 62.1% (CI: 45.6-76.2%), Philippines at 52.9% (CI: 30-74.5%), Malaysia at 28.9% (CI: 21.4-37.9%), and Singapore at 21% (CI: 8-45%). Subgroup analysis revealed that India consistently had the highest mortality rate for the past two decades (91.7% and 89.3%). The primary complication leading to mortality was encephalitis, accounting for 95% of cases. This systematic review and meta-analysis revealed a noteworthy surge in NiV mortality rates, particularly in the current decade (2014-2023). The escalation, with India reporting a concerning level of mortality of 89.3-91.7% in the past decades, signifies a pressing public health challenge.

PMID:39030703 | DOI:10.1080/20477724.2024.2380131