Severity Score Research Articles

Efficacy of xanomeline and trospium chloride in schizophrenia: pooled results from three 5-week, randomized, double-blind, placebo-controlled, EMERGENT trials

In the 5-week, randomized, double-blind, placebo-controlled EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) trials, xanomeline and trospium chloride (formerly known as KarXT) significantly improved symptoms of schizophrenia and was generally well tolerated. We pooled data from the EMERGENT trials to further characterize the efficacy of xanomeline/trospium and provide sufficient statistical power to analyze responses in participant subgroups. In pooled analyses, xanomeline/trospium significantly improved Positive and Negative Syndrome Scale (PANSS) total score at week 5 versus placebo (least squares mean difference, –9.9; 95% confidence interval, –12.4, –7.3; p < 0.0001; Cohen’s d effect size, 0.65). PANSS subscale and Clinical Global Impression–Severity scores also improved significantly with xanomeline/trospium versus placebo. Subgroup analyses consistently favored xanomeline/trospium over placebo regardless of differences in participant age, sex, race, body mass index, and baseline PANSS total score. These results add to existing evidence demonstrating robust and reliable improvements in symptoms with xanomeline/trospium across a broad spectrum of people with schizophrenia.

Outpatient inhaled corticosteroid use in bronchopulmonary dysplasia.

In the outpatient setting, inhaled corticosteroids (ICS) are frequently given to children with bronchopulmonary dysplasia (BPD) for treatment of respiratory and asthma-associated symptoms. In this study we sought to determine if correlations existed between ICS use and ICS initiation and patient characteristics and outpatient respiratory outcomes. This study included children with the diagnosis of BPD (n = 661) who were seen in outpatient pulmonary clinics at the Children's Hospital of Philadelphia between 2016 and 2021. Chart review was used to determine patient demographics, use and timing of ICS initiation, asthma diagnosis, and acute care usage following initial hospital discharge. At the first pulmonary visit, 9.2% of children had been prescribed an ICS at NICU discharge, 13.9% had been prescribed an ICS after NICU discharge but before their first pulmonary appointment, and 6.9% were prescribed an ICS at the completion of initial pulmonary visit. Children started on an ICS as outpatientshad a higher likelihood of ER visits (adjusted odds ratio: 2.68 ± 0.7), hospitalizations (4.81 ± 1.16), and a diagnosis of asthma (3.58 ± 0.84), compared to children never on an ICS. Of those diagnosed with asthma, children prescribed an ICS in the outpatient setting received the diagnosis at an earlier age. No associations between NICU BPD severity scores and ICS use were found. This study identifies an outpatient BPD phenotype associated with ICS use and ICS initiation independent of NICU severity score. Additionally, outpatient ICS initiation correlates with a subsequent diagnosis of asthma and acute care usage in children with BPD.

Interferon-gamma driven elevation of CXCL9: a new sepsis endotype independently associated with mortality

Endotype classification becomes the cornerstone of understanding sepsis pathogenesis. Macrophage activation-like syndrome (MALS) and immunoparalysis are the best recognized major endotypes, so far. Interferon-gamma (IFNγ) action on tissue macrophages stimulates the release of the cytotoxic chemokine CXCL9. It was investigated if this mechanism may be an independent sepsis endotype. In this cohort study, 14 patient cohorts from Greece, Germany and Italy were studied. The cohorts were 2:1 randomly split into discovery and validation sets. Sepsis was defined by the Sepsis-3 definitions and blood was sampled the first 24h from meeting the Sepsis-3 definitions. Concentrations of IFNγ, CXCL9, IP-10 (IFNγ induced protein-10), soluble CD163 and ferritin were measured. The endotype of IFNγ-driven sepsis (IDS) was defined in the discovery set as the combination of a) blood IFNγ above a specified cut-off associated with the minimal risk for immunoparalysis (defined as ≥8000 HLA-DR receptors on CD45/CD14-monoytes); and b) increase of CXCL9. Results were compared to the validation set. 5503 patients were studied; 3670 in the discovery set and 1833 in the validation set. IDS was defined as IFNγ more than 3pg/ml and CXCL9 more than 2200pg/ml. The frequency of IDS in the discovery set was 19.9% (732 patients; 95% confidence intervals-CIs 18.7-21.3%) and in the validation set 20.0% (366 patients; 95% CIs 18.2-21.9%). Soluble CD163, a marker of macrophage activation, was greater in IDS and IDS had features distinct from MALS. The mortality in IDS patients was 43.0% (315 patients; 95% CIs 39.5-46.6%) in the discovery set and 40.4% in the validation set (148 patients; 95% CIs 35.5-45.5%) (p=0.44 compared to patients of the discovery set). IDS was an independent risk factor for death in the presence of other endotypes, severity scores and organ dysfunctions of the multivariate model [hazard ratio 1.71 (95% CIs 1.45-2.01) in the discovery set and 1.70 (95% CIs 1.34-2.16) in the validation set]. Decreases of IFNγ and CXCL9 blood levels within the first 72h were associated with better outcome. IDS is a new sepsis endotype independently associated with unfavorable outcome. Hellenic Institute for the Study of Sepsis; Horizon 2020 project ImmunoSep; Swedish Orphan BioVitrum AB (publ) and German Federal Ministry of Education and Research.

Risk factors associated with overactive bladder severity in patients with type 2 diabetes.

The prevalence of overactive bladder (OAB) is known to be higher in patients with type 2 diabetes (T2DM) however there are not many studies about specific risk factors contributing to its progression among diabetes mellitus (DM) patients, so this study aimed to investigate the risk factors specific to DM that influence the progression of OAB in Syrian population. This cross-sectional study was carried out at five endocrinology centers situated in four Syrian provinces: Damascus, Aleppo, Homs, Hama, and Latakia. The study comprised patients who were diagnosed with both T2DM and OAB and had visited these centers from March 2020 and February 2024. The Arabic version of the OAB Symptom Score (OABSS) scale was used to categorize the participants based on the severity score into two groups: the mild OAB group and the moderate-severe OAB group. A logistic analysis was conducted to assess the risk factors associated with the progression of OAB among patients with diabetes. Among the 186 patients diagnosed with both DM and OAB, significant distinctions were found between the two groups concerning the severity of OAB, age, duration of diabetes, symptomatic diabetic peripheral neuropathy (DPN), and ankle reflex (p < 0.05). Furthermore, a multivariate analysis revealed that age (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.68-1.58), duration of diabetes (OR 2.14, 95% CI 1.75-3.74), and symptomatic DPN (OR 2.47, 95% CI 1.17-3.54) independently acted as risk factors for the advancement of OAB. The progression of OAB in Syrian patients with diabetes is closely associated with the severity of DM. Factors such as age, duration of diabetes, and symptomatic DPN are independent predictors of the severity of OAB. Patients who experience symptomatic DPN are at an increased risk of developing OAB.

Treatment Outcomes of Four-Implant-Retained Maxillary Palateless Overdenture: A 5-Year Observational Study.

Palateless overdentures (PLODs) provide advantages of improved taste perception and retention over conventional dentures. We aimed to evaluate 5-year outcomes of four implant maxillary PLODs. In this prospective observational study, edentulous participants were enrolled. A new conventional maxillary denture was prepared followed by implant placement and insertion of four implant retained maxillary PLOD. Oral health quality of life was assessed using the 49-item Oral Health Impact Profile (OHIP-49) at multiple intervals over 5 years along with biological and mechanical outcomes. Nine patients were evaluated at year 5. The mean age was 68 years, and six of the nine patients were males. The cumulative survival rate of implants was 100% while the implant success rate was 86%. Nylon retentive replacement was the most common encountered complication noted approximately four times per patient over 5 years. From a mean OHIP-49 severity score of 71.2 at baseline, severity scores decreased to 23.9 (p < 0.001) at year 1, denoting a clinically meaningful and statistically significant improvement in oral health quality of life. The lowered OHIP-49 severity scores remained stable throughout 5 years of follow-up. Four implant supported maxillary overdenture appears to have good patient perceived, biological and mechanical outcomes over 5 years. Fully powered studies are needed to replicate these findings.

MRPL41, as a target for acupuncture, promotes neuron apoptosis in models of ischemic stroke via activating p53 pathway

Neuronal death is the key cause of ischemic stroke. Acupuncture (Acu) is a recognized method for the treatment and amelioration of cerebral ischemia. However, the molecular mechanism of Acu for treating ischemic stroke has not yet been detailedly elucidated. Based our microarray analysis results, mitochondrial ribosomal protein L41 (MRPL41), which is related to apoptosis, was identified as the target of Acu. MRPL41 expression was increased in middle cerebral artery occlusion/reperfusion (MCAO/R) model and reduced after Acu treatment. Following, MCAO/R model and oxygen and glucose deprivation/reoxygenation (OGD/R) model were established to explore the effect of MRPL41. Knockdown of MRPL41 increased cell viability and ani-apoptotic protein (Bcl-2) expression, and reduced apoptosis intensity and pro-apoptotic protein (Bax and Cleaved caspase-3) of OGD/R neurons. In vivo, MRPL41 silencing decreased neurological severity score, shrank infarct area, reduced encephaledema and neuron apoptosis. In addition, reduction of MRPL41 caused loss of p53. Our data uncover that Acu targets MRPL41, following with inhibiting neuron apoptosis via p53 pathway, thereby ameliorating ischemic stroke.

Risk Factors for ARDS in Hospitalized Burn Patients: An Analysis of the National Trauma Data Bank.

Acute Respiratory Distress Syndrome (ARDS) is a common complication among mechanically ventilated adult burn patients; however, the risk factors associated with its development are not well understood. Conflicting evidence also exists regarding ARDS as an independent predictor of poor hospital outcomes. The purpose of this study is to identify risk factors for ARDS in mechanically ventilated adult burn patients and characterize the impact of ARDS on hospital course. The National Trauma Data Bank (NTDB) was queried for patients >=18 years with International Classification of Diseases (ICD) codes corresponding to burn injury from 2007-2016. Hospitalized patients with at least 48 hours of mechanical ventilation were included. Multivariate logistic regression were used to identify risk factors for ARDS. Propensity score-matched analysis at a 1:3 ratio was used to determine the impact of ARDS on hospital course. This sample included 13928 patients, of which 1437 (10.3%) developed ARDS. Hypotension in the Emergency Department, alcohol use disorder, total body surface area (TBSA), Injury Severity Score (ISS), and inhalation injury were independently associated with ARDS. In the propensity score-matched cohort, ARDS patients had a significantly longer median (interquartile range) length of stay (31 [15-54] vs. 22 [9-43], p<0.001). In-hospital mortality was also significantly higher in the ARDS cohort (203 [35%] vs. 325 [24%], p<0.001). These findings highlight the impact of patient and injury characteristics on developing ARDS and support the consideration of ARDS when estimating mortality risk in burn patients.

Daidzein ameliorates experimental traumatic brain injury-induced neurological symptoms by suppressing oxidative stress and apoptosis.

Traumatic brain injury (TBI) causes deficits in neurological function, induces pathological changes, and increases oxidative stress. The current investigation aimed to determine Daidzein's neuroprotective potential in experimental TBI. Initially, the HT-22 cell line exposed to H2O2 underwent in vitro examination, and the results showed that Daidzein had a neuroprotective effect evident from enhanced cell viability and decreased NO generation. Using three different Daidzein doses-1 mg/kg, 5 mg/kg, and 10 mg/kg-in the in vivo experiment, the potential of Daidzein was evaluated against TBI. The neurological severity score (NSS), kondziela's screen test, and elevated plus maze showed improvements after treatment with Daidzein manifested by decreased score, enhanced motor coordination, and anti-anxiety effects. Additionally, Daidzein improved mechanical allodynia and restored the breakdown of the blood-brain barrier. The FTIR spectral analysis showed restoration of the biochemical compositional changes. Furthermore, H & E and Toluidine blue staining revealed an improvement in the histopathological alterations. The RT-qPCR revealed an increase in mRNA expression level of Nrf2, HO-1, and Bcl-2 and the downregulation of Keap-1, Bax and Cleaved caspase-3 expressions. Thus, exhibiting its antioxidant and antiapoptotic potential. The RT-qPCR also manifested a decrease in mRNA expression of GFAP and Iba-1. Further immunohistochemistry results indicated Daidzein's antioxidant and antiapoptotic properties by upregulating Nrf2 and downregulating cleaved caspase-3. Daidzein also lowered the apoptosis index and improved neuronal survival evidenced by flow cytometric analysis. In addition to this, Daidzein notably increased the antioxidant enzyme levels and decreased the oxidative stress markers. The current study's findings point to the neuroprotective potential of the phytoestrogen Daidzein as it lessened neurological abnormalities, decreased oxidative stress, and lowered proapoptotic protein expression.

Beyond the Surgery: The Impact of Coping Strategies on Persistent Pain After Rotator Cuff Repair

Background: Rotator cuff repair is widely recognized as one of the most painful orthopedic surgeries, yet postoperative pain management in these patients is often underexplored. This study aimed to explore the relationship between pain outcomes and functional recovery six months after arthroscopic rotator cuff repair (ARCR), with a focus on the role of different pain coping mechanisms as mediators. Methods: This study included 83 patients that underwent rotator cuff repair. Pain levels were assessed using the Brief Pain Inventory (BPI-SF), while shoulder function was evaluated using the Oxford Shoulder Score (OSS). Coping strategies, including self-statements, ignoring pain, distraction, and praying, were examined in relation to pain severity and interference and were assessed with the Coping Strategies Questionnaire-Revised (CSQ-R). Simple and parallel mediation analyses were performed using the PROCESS macro to assess the mediating effects of coping mechanisms on the relationship between pain intensity, pain interference, and postoperative OSS. Results: Post-surgery, patients showed a significant improvement in OSS (from 29 ± 9 to 42 ± 6). At six months, 24% of patients reported chronic postsurgical pain (CPSP), defined as a pain severity score of 3 or higher. Correlation analyses revealed that OSS was negatively associated with pain catastrophizing (r = −0.35, p &lt; 0.01) and praying (r = −0.28, p &lt; 0.01). OSS was significantly negatively associated with pain severity (r = −0.54; p &lt; 0.01) and pain interference (r = −0.51, p &lt; 0.01). Mediation analysis demonstrated that coping self-statements significantly mediated the relationship between pain interference and shoulder function (a*b = 0.5266 (BootSE = 0.2691, 95% CI [0.1010, 1.1470]), emphasizing the important role of cognitive strategies in supporting recovery outcomes. Conclusions: Patients engaging in adaptive coping strategies, particularly coping self-statements, reported better functional outcomes. The findings underscore the importance of targeted interventions focusing on effective pain coping mechanisms to improve recovery post-ARCR.

Trauma Program Value Assessment at an Academic Health Network System Over 12 Years.

Trauma is a leading cause of global death, with 200000 deaths and over 3 million non-fatal injuries/year in the United States. We aim to assess trauma care value for patients who underwent urgent laparotomies (LAP) and thoracotomies (THO) in our Health Network System. Clinical variables (v = 84) from trauma patients (>18 yo) were retrieved retrospectively (Jan-2010 to July-2016) and prospectively (Aug-2016 to Sept-2021) from a Health System warehouse under IRB-approved protocols. Patients were divided according to their Injury Severity Score (ISS) into mild/moderate cases (ISS <15) and severe cases (ISS >15). Value was assessed using quality and cost domains. Quality surrogates included graded postoperative complications (PCs), length of stay (LOS), 30-day readmission (RA), patient satisfaction (PS), and textbook (TB) cases. Total charges (TCs) and reimbursement index (RI) were included as surrogates for cost. Value domains were displayed in scorecards comparing Observed (O) with Expected (E) (using the ACS risk calculator) outcomes. Uni-/multivariate analyses were performed using SPSS. 41,927 trauma evaluations were performed, leading to 16044 admissions, with 528 (3.2%) patients requiring urgent surgical procedures (LAP = 413 and THO = 115). Although the M:F ratio (7:3) was similar in LAP vs THO groups, age and BMI were significantly different (41.8 ± 19.1 vs 51.8 ± 19.9 years, 28.6 ± 9.9 vs 27.4 ± 7Kg/m2, respectively, P < .05). Blunt trauma was involved in 68.8/77.3% of the LAP/THO procedures, respectively (P < .05). Multivariate analyses showed ISS, age, ASA class, and medical center as factors significantly predicting PC (P < .05). Postoperative complication grades from the LAP/THO groups showed above-average outcomes; nonetheless, LOS was higher than the national averages. The Trauma Program holds high value in our Health Network System. Protocols for decreasing LOS are being implemented.

Ipsilateral Femoral Neck and Shaft Fractures: Complex Injuries With High Rates of Femoral Shaft Nonunion.

To investigate nonunion rates and risk factors in patients with ipsilateral femoral neck and shaft fractures. Retrospective review. Two Level I trauma centers. Two hundred seven patients treated for ipsilateral femoral neck (AO/OTA 31-B) and shaft (AO/OTA 32A-C) fractures from 2013 to 2022. Patients with less than 6 months of follow-up were excluded. The primary outcome of this study was femoral shaft nonunion. Risk factors for nonunion were evaluated, including smoking, open fracture, delay to full weight-bearing, blood transfusions, and AO/OTA classification. Two hundred twenty-seven patients were initially identified, but only 154 patients had sufficient follow-up and were included in final analysis. The mean age was 38.9 years (SD = 15.3), and injury severity score was 19.5 (9.7). One hundred ten patients (71%) were male and 69 (45%) required intensive care unit care. Thirty-eight patients (25%) experienced an open fracture, and 44 fractures (29%) were AO/OTA Type C. Thirty patients (20%) underwent initial external fixation, and 88 patients (57%) received a perioperative transfusion. Thirty-four patients (22%) developed a femoral shaft nonunion, and 5 (3%) experienced a surgical site infection. Nonunion was associated with perioperative blood transfusion, AO/OTA Type C fracture, postoperative non-weight-bearing, and delay to full weight-bearing ≥12 weeks. Multivariable regression identified perioperative blood transfusion ≥3 (risk ratio [RR] = 1.91; CI, 1.12-2.72; P = 0.02) and AO/OTA Type C fracture (RR = 2.45; CI, 1.50-3.34; P = 0.001) as independent risk factors. Ipsilateral femoral neck and shaft fractures remain difficult injuries to treat. Much attention is given to diagnosis and treatment of the femoral neck component. These results suggest that successful treatment of the femoral shaft component presents its own challenges with high nonunion rates. Prognostic Level III.

No benefit from the addition of low-dose ketamine infusion to standard evidence-based care of patients with multiple rib fractures.

Multiple rib fractures from blunt thoracic trauma cause significant morbidity. Optimal current management includes multimodal analgesia, pulmonary hygiene, and early mobilization. Low-dose ketamine infusion (LDKI) has been proposed as an adjunctive analgesic in this setting. A prior study reported decreased pain scores with LDKI in patients with multiple rib fractures. We hypothesized that LDKI would decrease morphine milligram equivalents (MMEs) in patients with multiple rib fractures. A prospective randomized placebo-controlled trial was performed in adult (18 years or older) patients with three or more rib fractures. A prestudy power analysis calculated an 80% chance of identifying a 15% decrease in MMEs with 50 subjects. The study was approved by the institutional review board and informed consent obtained in all subjects. Demographic (age, sex) and injury specific information (Injury Severity Score, number of rib fractures) were obtained. Subjects were randomized 1:1 to receive continuous LDKI (0.1 mg/kg/h) or placebo infusion (0.9% NaCl) for ≤48 hours. All patients received a standard evidence-based multidisciplinary protocol for rib fractures management. Primary outcome measure was MME use or pulmonary complications. Statistical comparison of LDKI versus placebo was performed using the Mann-Whitney U test. All 50 enrolled subjects (placebo, 25; LDKI, 25) received study drug infusion. The two groups were well matched for age, Injury Severity Score, and number of rib fractures. We observed no differences in the Day 1 (p = 0.961), Day 2 (p = 0.373), or total MMEs (p = 0.946) between groups. Similar total MME use was observed when subjects who received ≥40 hours of study drug and were compared (p = 0.924). Use of LDKI did not alter subsequent need for opiate analgesics postinfusion, hospital length of stay, pulmonary complications, or need for readmission. The addition of LDKI to an established multimodal, evidence-based protocol for management of multiple rib fractures did not decrease opiate usage or impact pulmonary complications. Therapeutic/Care Managaement; Level I.

Metabolic Syndrome Severity Score in Subjects with and without Poly Cystic Ovarian Syndrome

Objective: To compare polycystic ovarian syndrome and their defining criteria with metabolic syndrome severity score among females with and without polycystic ovarian syndrome. Study Design: Comparative cross-sectional study. Place and Duration of Study: Naval Hospital Islamabad, from Jan 2018 to Dec 2021. Methodology: We evaluated 293 female subjects for Poly Cystic Ovarian Syndrome after several exclusions who presented with an initial complaint of disturbances in menstrual cycles. These subjects underwent clinical examination including blood pressure and anthropometric indices and measurements of modified Ferriman Gallway score. Biochemical measurements included fasting plasma glucose, HDL cholesterol, triglycerides and insulin measurement. These parameters were measured for various components included in defining the Poly Cystic Ovarian Syndrome as per Rotterdam criteria and Metabolic Syndrome Severity Score equation to compare metabolic syndrome severity and insulin resistance among subjects with Poly Cystic Ovarian Syndrome and without Poly Cystic Ovarian Syndrome. Results: Mean age among participants were 29.46±6.74 years. Disturbances in menstrual cycle reporting oligo/anovulation was reported by (181/293) 61.8% in comparison to (112/293) 38.2%. Hirsutism (modified Ferriman Gallway score&gt;8) was present in (142/293) 48.5%. Radiological findings pointing towards Poly Cystic Ovarian Syndrome diagnosis were found in (72/293) 24.6%. Metabolic Syndrome Severity Score showed higher correlation with age, and insulin resistance in contrast to hirsutism and free androgen indices. Hirsutism was higher among oligo/anovulation females than participants without menstrual complaints (14.17+8.99 vs. 11.16+7.88, p=0.004). Similarly, bioc Conclusion: Metabolic Syndrome Severity Score equation does not associate with Poly Cystic Ovarian Syndrome criteria as defined by Rotterdam. Insulin resi

Agreement for posttraumatic stress symptoms among unaccompanied young refugees and professional caregivers

ABSTRACT Background: Prevalence rates for posttraumatic stress symptoms (PTSS) in unaccompanied young refugees (UYRs) are high. Research with biological parents indicates low agreement rates between self and caregiver reports for PTSS, although caregivers play an important role as gatekeepers to ensure appropriate treatment. Objective: This study examines youth and caregiver agreement on the endorsement of different trauma types, the PTSS severity score and symptom clusters, as well as the potential association between youth factors (age, comorbidity, and duration in facility) and disagreement. Method: The sample consisted of N = 610 UYRs, aged M = 16.75 (SD = 1.33, range: 12–20) years. Of these, 91.0% were male, and 43.4% were from Afghanistan, currently residing in German children and youth welfare facilities. Results: Agreement rates across trauma types were poor (accidental trauma: Cohen’s k = .13; community violence: Cohen’s k = .07; domestic violence: Cohen’s k = .19; sexual abuse: Cohen’s k = .38). Agreement rates for the PTSS severity score (ICC = .22) and symptom clusters were poor (re-experiencing: ICC = .27; avoidance: ICC = .02; negative alterations in cognitions and mood ICC = .12; hyperarousal: ICC = .25), with youth reporting significantly higher scores. Regression models showed that having comorbid symptoms and a shorter duration in the facility were associated with higher disagreement at the PTSS severity score (Adjusted ­R 2 = .21) and across symptom clusters (re-experiencing: Adjusted ­R 2 = .13; avoidance: Adjusted ­R 2 = .07; negative alterations in cognitions and mood: Adjusted ­R 2 = .16; hyperarousal: Adjusted­ R 2 = .16). Age was not significantly associated with disagreement rates. Conclusion: It is important to enhance the awareness and comprehension of caregivers regarding recognition of mental illnesses and their symptoms as well as assessing mental health among UYRs.

Galangin Regulates Astrocyte Phenotypes to Ameliorate Cerebral Ischemia-reperfusion Injury by Inhibiting the RhoA/ROCK/LIMK Pathway.

This study aimed to explore whether Galangin (Gal) could improve cerebral Ischemia- reperfusion (I/R) injury by regulating astrocytes, and clarify its potential molecular mechanism. An I/R injury model of rats was established using the Middle Cerebral Artery Occlusion/Reperfusion (MCAO/R) method, followed by the administration of Gal (25, 50, 100 mg/kg) via gavage for 14 consecutive days. Besides, astrocytes were isolated from the rats to construct an Oxygen-Glucose Deprivation/Re-oxygenation (OGD/R) cell model, with treatments of Gal or the Ras homolog gene family member A (RhoA)/Rho-associated Coiled-coil containing protein Kinase (ROCK) inhibitor Y-27632. Subsequently, the severity of nerve injury was assessed using the modified Neurological Severity Score (mNSS) test; behavioral disorders in I/R rats were observed through the open field and ladder-climbing tests. Pathological damages and neuron survival in the peri-infarct zone were examined by hematoxylin and eosin staining and NeuN staining, respectively. Additionally, immunofluorescence staining was employed to determine astrocyte polarization and TUNEL staining was carried out to measure the level of cell apoptosis; also, western blot was performed to detect the expression of proteins related to the RhoA/ROCK/LIM domain Kinase (LIMK) pathway. Gal significantly ameliorated the neurological and motor dysfunctions caused by I/R in rats, reduced pathological damage in the peri-infarct zone, and promoted neuronal survival. Additionally, Gal increased the number of A2 astrocytes, while it decreased the number of A1 astrocytes. In vitro experiments revealed that the effect of Gal was consistent with that of Y-27632. Additionally, Gal significantly enhanced the survival of OGD/R cells, increased the number of A2 astrocytes, and inhibited the expression of proteins associated with the RhoA/ROCK pathway. Gal could reduce the level of apoptosis, promote the polarization of A2 astrocytes, and improve cerebral I/R injury, and its mechanism may be related to the inhibition of the RhoA/ROCK pathway.

Differences in Prevalence and Psychosocial Characteristics of Irritable Bowel Syndrome According to Rome III and Rome IV Criteria in Medical and Nursing Students.

In Korea, changes in the prevalence of irritable bowel syndrome (IBS) after the Rome IV update have not been extensively studied. The aim of this study is to compare the prevalence and psychosocial risk factors of IBS according to Rome III and Rome IV criteria in medical and nursing students. From August 13, 2021 to October 22, 2021, participants were enrolled and surveyed online. The survey includes general and specific questions for disease diagnosis and regarding participants' social and psychological characteristics using the 36-item short form survey, the Brief Encounter Psychosocial Instrument-Korean version, and the Hospital Anxiety and Depression Scale. In total, 338 medical students and 102 nursing students completed the survey. IBS was diagnosed in 78 students (17.7%) using Rome III criteria and in 51 students (11.6%) using Rome IV criteria. Significant differences in physical functioning score and severity score were observed between patients diagnosed using Rome IV criteria and patients diagnosed using Rome III criteria. Multiple logistic regression revealed that severity score (adjusted odds ratio = 1.01; 95% confidence interval: 1.00-1.21; P = 0.022) is the only predictor of IBS that differentiates Rome IV criteria from Rome III criteria. Even after updating the Rome IV diagnostic criteria, the prevalence of IBS in medical and nursing students in Korea remained high. Patients who met the Rome IV criteria had more severe symptoms and lower quality of life than patients who met the Rome III criteria.

Robust extraction of pneumonia-associated clinical states from electronic health records

Mining of electronic health records (EHR) promises to automate the identification of comprehensive disease phenotypes. However, the realization of this promise is hindered by the unavailability of generalizable ground-truth information, data incompleteness and heterogeneity, and the lack of generalization to multiple cohorts. We present here a data-driven approach to identify clinical states that we implement for 585 critical care patients with suspected pneumonia recruited by the SCRIPT study, which we compare to and integrate with 9,918 pneumonia patients from the MIMIC-IV dataset. We extract and curate from their structured EHRs a primary set of clinical features (53 and 59 features for SCRIPT and MIMIC-IV, respectively), including disease severity scores, vital signs, and so on, at various degrees of completeness. We aggregate irregular time series into daily frequency, resulting in 12,495 and 94,684 patient-day pairs for SCRIPT and MIMIC, respectively. We define a "common-sense" ground truth that we then use in a semisupervised pipeline to optimize choices for data preprocessing, and reduce the feature space to four principal components. We describe and validate an ensemble-based clustering method that enables us to robustly identify five clinical states, and use a Gaussian mixture model to quantify uncertainty in cluster assignment. Demonstrating the clinical relevance of the identified states, we find that three states are strongly associated with disease outcomes (dying vs. recovering), while the other two reflect disease etiology. The outcome associated clinical states provide significantly increased discrimination of mortality rates over standard approaches.

A Pilot Study of the Effectiveness of a Short Course of Rifaximin 2200 mg/day on Abdominal Symptoms and its Effects on Quality of Life in Patients with Moderate to Severe Diarrhea-Predominant Irritable Bowel Syndrome.

Rifaximin is used to treat diarrhea-predominant irritable bowel syndrome (IBS-D). However, determining the most effective regimen remains a challenge. This study aimed to evaluate the effectiveness and safety of a 10-day high-dose course of rifaximin (2200 mg/day) and its effects on both abdominal symptoms and quality of life (QOL) in patients with IBS-D. Adult patients with moderate to severe IBS-D (Rome IV) and fecal urgency and bloating were prescribed rifaximin 1100 mg twice daily for 10 days. Demographic information, the IBS Symptom Severity Index (IBS-SSI) score (using a 7-point Likert scale), and Bristol Stool Scale (BSS) score were recorded at baseline, day 10, and 4 weeks after treatment cessation. IBS Symptom Severity Score (IBS-SSS) and IBS-QOL scores were recorded at baseline and day 10. Any drug adverse effects were recorded. In total, 39 patients completed the study. Average scores for all abdominal symptoms and BSS showed significant improvement at day 10 and 4 weeks after treatment cessation (all p < 0.001). A significant improvement was seen in IBS-SSS and overall IBS-QOL score at day 10 (p < 0.001), with the highest improvement (31%) in interference with activity. Moreover, composite improvement rates were 38.64% for all abdominal symptoms, together with BSS < 5, bi-composite (66.67% for abdominal pain + bloating; 61.54% for abdominal pain + urgency), and 56.41% for tri-composite (abdominal pain + bloating + urgency) symptoms. Notably, no serious adverse effects were reported, and the adherence rate was 94.9%. Abdominal symptoms and overall QOL, especially in social and work dimensions, significantly improved in patients with moderate to severe IBS-D following a regimen of rifaximin 2200 mg/day, which was well tolerated.

Prevalence and Level of Depression, Anxiety and Stress Among Frontliners Using the Depression, Anxiety and Stress Scale (DASS)-21 in a Tertiary Hospital in Manila, Philippines During the COVID-19 Pandemic: a Cross-Sectional Study

Background: COVID-19 was declared as a pandemic by the World Health Organization (WHO) in March 2020. It has affected millions globally and remains as a public health concern until today. Objectives: The study aims to identify the prevalence of depression, anxiety and stress among UST hospital frontliners during the COVID-19 pandemic using the Depression, Anxiety and Stress Scale (DASS)-21 scale. Methods: A cross-sectional study was conducted among 272 frontliners in a tertiary hospital in Manila, Philippines using the DASS-21 scale. Results: Based on data gathered from the responses of participants using the DASS-21 scale, the prevalence of depression, anxiety and stress among the frontliners were 28.68%, 35.66% and 14.71%, respectively. Being single, living alone, higher degree of educational attainment (postgraduate), trainees (residents and fellows) and those having pulmonary comorbidities were associated with increasing level of depression and stress. Respondents who had less work experience (less than 5 years) had significant depression; being single presented with higher anxiety; and those who had a previous COVID-19 infection had higher degree of stress. Conclusion: Several demographic and occupational characteristics, in accordance to the COVID-19 pandemic, yielded significant results regarding the presence of depression, anxiety and stress. The study recommends closer follow-up of participants which recorded high severity scores in the DASS-21 scale as well as regular psychological briefing and counseling to assess if there are other contributory factors to such responses. Ultimately, this may enlighten us on how to provide holistic care to our own hospital staff. Keywords: COVID-19, Depression, Anxiety, Stress, DASS-21 scale

Current Self-reported Pain Before and After Cure of Hepatitis C Among Persons Who Actively Inject Drugs.

Questions remain on the relationship between pain and hepatitis C virus cure among persons who inject drugs (PWID). This study aimed to explore whether achieving hepatitis C virus cure reduced pain severity. Prespecified secondary analysis utilized data from a pragmatic clinical trial of care delivery models that enrolled PWIDs between 2016 and 2018 and treated with sofosbuvir/velpatasvir. Current pain severity (0-100) was assessed before and after treatment and 5-point Likert pain scales were used to determine moderate or greater current pain at baseline; the duration and etiology of current pain were not assessed. We used generalized mixed-effects linear models to test whether achieving sustained virologic response (SVR), that is, cure, was associated with lower numeric pain scores (primary outcome) posttreatment, adjusting for potential confounders (age, sex, intervention assignment, time/visit, and baseline pain severity category) and to examine changes in pain over time. Adjusted means estimated from a fitted model for pain severity at each visit were compared between participants who did and did not achieve SVR, both for the sample overall and for the subsample of participants who reported moderate or greater pain at baseline. Of the 501 participants who were randomized, treated with DAAs and had SVR data, moderate or greater pain was reported at baseline in 174 (34.7%) of participants. Numeric pain severity did not significantly differ by SVR status at any study visit except for the week 48 visit from baseline, when the estimated pain score was significantly higher for those who failed treatment (38.0 vs 26.3, P = 0.033). Among the subsample with baseline moderate or greater pain, pain severity scores were significantly lower in subsequent visits compared to the baseline visit, with the exception of week 48 among participants who did not achieve SVR. Among PWID, achieving SVR did not improve pain severity. However, participants who failed treatment had significantly greater pain at the visit immediately following visit for SVR, which may relate to adverse psychological effects of treatment failure. Among those with baseline moderate or greater pain, pain scores declined post treatment, suggesting that treatment itself (irrespective of SVR) may be associated with improved pain.