JAMA. 2022 Sep 27;328(12):1258-1259. doi: 10.1001/jama.2022.13600.
NO ABSTRACT
PMID:36166034 | DOI:10.1001/jama.2022.13600
Clin Transl Sci. 2022 Sep 27. doi: 10.1111/cts.13362. Online ahead of print.
ABSTRACT
Clinical pharmacology is an integral discipline supporting the development, regulatory evaluation, and clinical use of drugs for the treatment of both common and rare diseases. Here, we evaluated the recommendations and information available from select clinical pharmacology studies in the therapeutic product labeling of new molecular entities (NMEs) approved from 2017 to 2019 for both common and rare diseases. A total of 151 NMEs, including 72 orphan and 79 non-orphan drugs, were analyzed for recommendations and information available related to food-drug interaction, drug-drug interaction, renal impairment, hepatic impairment, QT assessment, and human radiolabeled mass balance studies using data collected from the original labeling and other regulatory documents. The analysis showed no statistically significant difference in the recommendations between orphan and non-orphan drugs except for renal impairment related recommendations in section 8 of the labeling. Although not significant, fewer hepatic impairment labeling recommendations were available for orphan drugs when compared with non-orphan drugs. At the time of initial approval, 79 postmarketing requirements (PMRs) and postmarketing commitments (PMCs) for 33 orphan drugs and 39 PMRs and PMCs for 19 non-orphan drugs were established; with most difference observed for drug-drug interaction, hepatic impairment, and QT assessment. Overall, although there was a trend for more labeling recommendations and fewer postmarketing studies and clinical trials for non-orphan drugs, there appeared to be no substantial differences in how these select clinical pharmacology studies are leveraged during the development and approval of orphan and non-orphan drugs.
PMID:36165094 | DOI:10.1111/cts.13362
N Z Vet J. 2022 Sep 27:1-12. doi: 10.1080/00480169.2022.2129854. Online ahead of print.
ABSTRACT
AIMS: To describe basic husbandry (veterinary care, substrate and bedding, toys, frequency of cleaning) provided to guinea pigs (Cavia porcellus) by a sample of owners in New Zealand.
METHODS: Respondents were invited to complete a survey disseminated through the social media channels of animal interest and advocacy groups (3 September 2020 to 3 November 2020). Respondents who agreed to participate were asked a range of questions regarding provision of husbandry to their oldest pet guinea pig. Descriptive statistics are reported here relating to husbandry, length of ownership, provision of substrate, bedding and toys, frequency of cleaning and veterinary care.
RESULTS: A total of 503 responses were received, of which 329 complete responses were analysed. Of these respondents, 208/329 (63.2%) had owned guinea pigs for more than 2 years. Most owners provided a cage with a wooden base as substrate (144/321, 44.9%), bedding (308/329; 93.6%) and toys (169/329; 51.1%). Half (176/329; 53.5%) of respondents reported taking their guinea pig to a veterinarian. Just over half of owners surveyed cleaned water (165/329; 50.1%) and food (181/329; 55.0%) bowls daily, and a third picked up droppings (109/329; 33.1%) daily.
CONCLUSIONS AND CLINICAL RELEVANCE: While owners provided an array of toys, and a range of bedding and substrate types to their guinea pigs, cages were cleaned out less frequently than recommended, and it was common for guinea pig cages to be cleaned out less frequently than recommended. Future research is required to provide robust and evidence-based links between husbandry and the welfare of pet guinea pigs.
PMID:36165091 | DOI:10.1080/00480169.2022.2129854
Eur J Gastroenterol Hepatol. 2022 Sep 20. doi: 10.1097/MxhEG.0000000000002449. Online ahead of print.
ABSTRACT
OBJECTIVES: Postoperative endothelial damage potentially results in increased vascular leakage, tissue edema and subsequent complications. The preventive effect of glucocorticoids on endothelial damage after surgery is sparsely described, including the relation between endothelial damage and the postoperative inflammatory response. Thus, we aimed to assess the preventive effect of high-dose glucocorticoids on postoperative endothelial damage, and the association between endothelial damage and inflammation after surgery.
METHODS: This was a predefined substudy of a randomized double-blinded clinical trial of methylprednisolone 10 mg/kg (high dose) vs. dexamethasone 8 mg (low dose) in patients undergoing liver resection at Rigshospitalet, Copenhagen. In total 25 patients undergoing major liver resection (11 in the high-dose group and 14 in the low-dose group) were included. The primary outcome was changed in five endothelial biomarkers and the secondary outcome was changes in inflammation [C-reactive protein (CRP)] for the first three postoperative days.
RESULTS: No statistically significant difference was found for any endothelial biomarkers postoperatively between the two groups (P > 0.15, for all). High-dose glucocorticoids significantly reduced CRP on day 3 compared to low-dose glucocorticoids [median difference on a postoperative day 3, 59.6 g/L, (84.2; 27.1), P < 0.002]. No significant correlation between endothelial damage and CRP levels was seen.
CONCLUSIONS: No significant effect of high- vs. low-dose glucocorticoids on development in endothelial biomarkers after major liver resection was observed. High-dose glucocorticoids reduce the inflammatory response though without correlation to endothelial damage. Future studies should assess the clinical impact of increased endothelial biomarkers for clinical perioperative outcomes.
PMID:36165063 | DOI:10.1097/MxhEG.0000000000002449
Eur J Gastroenterol Hepatol. 2022 Sep 12. doi: 10.1097/MEG.0000000000002451. Online ahead of print.
ABSTRACT
BACKGROUND: At present, little is known about the risk factors of early postoperative death in patients with hepatocellular carcinoma (HCC).
METHODS: We collected the data of patients who were diagnosed with primary liver cancer between 2010 and 2015 in the Surveillance, Epidemiology, and End Results database and further allocated them to the training set and validation set. Univariate and multivariate logistic regression analysis was used to determine the independent influencing factors of early postoperative death of HCC patients. Random forest and Least absolute shrinkage and selection operator regression analysis were used to screen out vital variables for the construction of the nomogram. It was evaluated by receiver operating characteristic curve, calibration curve and decision curve analysis.
RESULTS: A total of 4154 patients were selected in this process, including 2647 patients with postoperative early death (outcome1) and 1507 patients with liver cancer-specific postoperative early death (outcome2). Surgery method, age category, marital status and tumor grade were the risk factors for early postoperative death. As for the liver cancer-specific early postoperative death, AJCC, surgery method, chemotherapy and tumor grade were independent prognostic factors. Early death and liver cancer-specific early death nomograms have an area under curves of 0.643 and 0.679 in the training set, respectively, and 0.617 and 0.688 in the validation set. The calibration curve and decision curve analysis shows that the nomograms have good performance.
CONCLUSION: This model provides an intuitive and practical tool for future studies based on large-scale cohorts by exploring the risk factors of early death in patients with HCCs undergoing surgery.
PMID:36165060 | DOI:10.1097/MEG.0000000000002451
Eur J Gastroenterol Hepatol. 2022 Aug 25. doi: 10.1097/MEG.0000000000002432. Online ahead of print.
ABSTRACT
BACKGROUND AND OBJECTIVES: Wilson’s disease (WD) is an inherited disorder with perturbations in copper metabolism and can cause multiorgan damage. This study aims to explore cardiac findings mainly based on electrocardiography (ECG) in WD patients.
METHODS: We retrospectively enrolled adult patients who were diagnosed with WD between January 2011 and December 2020. Demographic and clinical data were collected and reevaluated.
RESULTS: A total of 126 patients were included. There were 71 men and 55 women. The mean age was 27.2 years. Ninety-nine had hepatic presentation as the initial symptom and 27 had neuropsychiatric presentation as the initial symptom. Thirty-seven patients (29.4%) had cardiac manifestations. Of these patients, nine presented apparent cardiac symptoms (three with discontinuous chest tightness, three with dizziness, two with palpitation and one with atypical chest pain) and 28 had asymptomatic electrocardiography (ECG) abnormalities. Among the nine patients, four had second- or third-degree atrioventricular block, three had ST-segment change and two had ventricular tachycardia. ECG abnormalities in the 28 patients included increase in the width of the QRS complex in 8, atrial premature beats in 8, T-wave inversion in 5, P-wave inversion in 2, sinus bradycardia in 2, ST-segment change in 2, and coexistence of sinus bradycardia and T-wave inversion in 1. No statistical difference (P = 0.32) existed in the occurrence of ECG abnormalities between patients with hepatic presentation (27/99) and those with neuropsychiatric presentation (10/27).
CONCLUSION: Cardiac involvement is not rare in adult WD patients. We suggest that cardiac evaluation should be routinely performed in the population.
PMID:36165059 | DOI:10.1097/MEG.0000000000002432
Curr Opin Gastroenterol. 2022 Sep 21. doi: 10.1097/MOG.0000000000000875. Online ahead of print.
ABSTRACT
PURPOSE OF REVIEW: Several recent studies have corroborated a strong association between diet and gastric cancer risk; investigators have also identified dietary factors that protect against gastric cancer. This review summarizes the literature on this topic and guides future research directions.
RECENT FINDINGS: High-salt intake disrupts the gastric mucosal defense barrier, promoting Helicobacter pylori colonization and penetration of other carcinogenic compounds. Processed foods, processed meats, red meat, alcohol, foods with high dietary fat, and dietary cholesterol increase the risk of gastric carcinogenesis. On the other hand, increased consumption of fruits, vegetables, whole grains, nuts, and a low-salt diet may offer a protective effect.
SUMMARY: Despite decreases in gastric cancer incidence because of increased identification and treatment of H. pylori, gastric cancer remains one of the most common cancers worldwide with a high mortality rate. This disturbing statistic highlights the importance of reducing and eliminating other risk factors for gastric cancer. There is a strong body of evidence that alcohol, processed foods, high salt intake, high fat intake, and foods with animal products (meats, eggs, and dairy) increase the risk of gastric cancer. A diet that is high in whole grains, fruits, vegetables, nuts and is low in salt may reduce the risk of gastric cancer.
PMID:36165035 | DOI:10.1097/MOG.0000000000000875
Arch Suicide Res. 2022 Sep 27:1-10. doi: 10.1080/13811118.2022.2127386. Online ahead of print.
ABSTRACT
OBJECTIVE: Suicide bereavement is a significant public health concern. Using nationally representative survey data, we quantify sexual orientation differences in frequency of suicide exposure and suicide exposure-related emotional distress among US adults.
METHODS: We used cross-sectional data from the 2016 General Social Survey (GSS) and included sexual minority (i.e., lesbian, gay, bisexual; (n = 74, 5.3%) and heterosexual (n = 1,207, 94.7%) adults. The GSS asked several questions related to suicide exposure including number of lifetime suicide exposures, emotional distress related to suicide exposure, time elapsed since suicide exposure, and relationship(s) and perceived closeness to the person(s) who died. We use descriptive statistics to describe differences in suicide exposure characteristics across sexual orientation. Among those who were exposed to at least one suicide (n = 698, 51.1%), a weighted multivariable logistic regression model examined the association between sexual orientation and suicide exposure-related emotional distress adjusting for confounders.
RESULTS: Sexual minorities reported a similar number of lifetime suicide exposures and were not significantly different from heterosexuals on other suicide exposure characteristics. However, sexual minority, compared to heterosexual, respondents experienced 3.14 greater odds of severe emotional distress related to suicide exposure (95% CI = 1.42-6.94, p = .005).
CONCLUSION: Perhaps due to stigmatizing mourning experiences, sexual minority adults are particularly vulnerable to severe suicide exposure-related emotional distress. Future research to understand the scope of sexual minority-specific bereavement support services and public policies (e.g., bereavement leave) as well as intervention development to support sexual minority adults’ coping in the wake of suicide exposure is warranted. HIGHLIGHTSApproximately half of sexual minority US adults report a lifetime suicide exposureSexual minority adults experience more severe suicide exposure-related emotional distressPostvention care should be tailored to meet the needs of sexual minority adults.
PMID:36165026 | DOI:10.1080/13811118.2022.2127386
Psychol Med. 2022 Sep 27:1-13. doi: 10.1017/S0033291722002628. Online ahead of print.
ABSTRACT
BACKGROUND: Treatment non-response and recurrence are the main sources of disease burden in major depressive disorder (MDD). However, little is known about its neurobiological mechanism concerning the brain network changes accompanying pharmacotherapy. The present study investigated the changes in the intrinsic brain networks during 6-month antidepressant treatment phase associated with the treatment response and recurrence in MDD.
METHODS: Resting-state functional magnetic resonance imaging was acquired from untreated patients with MDD and healthy controls at baseline. The patients’ depressive symptoms were monitored by using the Hamilton Rating Scale for Depression (HAMD). After 6 months of antidepressant treatment, patients were re-scanned and followed up every 6 months over 2 years. Traditional statistical analysis as well as machine learning approaches were conducted to investigate the longitudinal changes in macro-scale resting-state functional network connectivity (rsFNC) strength and micro-scale resting-state functional connectivity (rsFC) associated with long-term treatment outcome in MDD.
RESULTS: Repeated measures of the general linear model demonstrated a significant difference in the default mode network (DMN) rsFNC change before and after the 6-month antidepressant treatment between remitters and non-remitters. The difference in the rsFNC change over the 6-month antidepressant treatment between recurring and stable MDD was also specific to DMN. Machine learning analysis results revealed that only the DMN rsFC change successfully distinguished non-remitters from the remitters at 6 months and recurring from stable MDD during the 2-year follow-up.
CONCLUSION: Our findings demonstrated that the intrinsic DMN connectivity could be a unique and important target for treatment and recurrence prevention in MDD.
PMID:36164996 | DOI:10.1017/S0033291722002628
Eur J Prosthodont Restor Dent. 2022 Sep 16. doi: 10.1922/EJPRD_2429Karabay14. Online ahead of print.
ABSTRACT
OBJECTIVES: To evaluate the clinical performance of universal adhesives with self-etch mode regarding their functional monomer and HEMA contents.
METHODS: The study involved 27 patients (108 restorations) aged between 34 and 69 (mean age: 53.8). Each restoration contained one of four different universal adhesives applied in self-etch mode: G-Premio Bond (HEMA-free, MDP and 4-MET containing), Xeno Select (HEMA and MDP-free), Tetric-n-Bond Universal (HEMA and MDP-containing) and Clearfil Universal Bond Quick (HEMA, MDP and amide monomers containing). The restorations were evaluated according to the FDI criteria at baseline, 6, and 12 months. The data were statistically analyzed using Friedman’s and Kruskal-Wallis tests for significance in each pair (p⟨0.05).
RESULTS: After 12 months, one restoration was lost in each of the G-Premio Bond and Clearfil Bond Quick groups. The success rate was 96.3% for both adhesives and 100% for Xeno Select and Tetric-n-Bond adhesives. There was no statistically significant difference between the four dentin adhesive groups among all the evaluation periods regarding any evaluation criteria. However, four universal adhesives showed clinically acceptable marginal discoloration and marginal deterioration in a few restorations.
CONCLUSION: Monomer contents of universal adhesives with self-etch mode had no significant effect on the success of restorations.
PMID:36164992 | DOI:10.1922/EJPRD_2429Karabay14