Nevin Manimala

J Pediatr Gastroenterol Nutr. 2023 Jul 1;77(1):121-125. doi: 10.1097/MPG.0000000000003791. Epub 2023 Apr 19.

ABSTRACT

Chronic hepatitis B viral (HBV) infection is associated with significant morbidity and mortality with endemic areas carrying most of the global burden of HBV disease. Current HBV screening rates in the United States are suboptimal. We aimed to improve HBV screening rates at regional family health centers serving high-risk refugee populations by 20% over 2 years. We used quality improvement (QI) methodology and implemented interventions providing electronic medical record (EMR)-enabled HBV screening tools within known clinical workflows. EMR tools captured country-of-origin data to identify persons from HBV-endemic regions with provision of a laboratory order set to ensure performance of appropriate HBV screening tests. The project was initiated prior to the COVID pandemic but continued during the pandemic with imposed social isolation measures. We nevertheless demonstrated 4 statistical process control chart shifts and achieved our QI smart aim. Further, we demonstrated a high HBV detection rate (8.2%-12.8%) among persons identified for screening.

PMID:37326849 | DOI:10.1097/MPG.0000000000003791

Transl Stroke Res. 2023 Jun 16. doi: 10.1007/s12975-023-01164-2. Online ahead of print.

ABSTRACT

Repulsive guidance molecule A (RGMa) is an inhibitor of neuronal growth and survival which is upregulated in the damaged central nervous system following acute spinal cord injury (SCI), traumatic brain injury, acute ischemic stroke (AIS), and other neuropathological conditions. Neutralization of RGMa is neuroprotective and promotes neuroplasticity in several preclinical models of neurodegeneration and injury including multiple sclerosis, AIS, and SCI. Given the limitations of current treatments for AIS due to narrow time windows to intervention (TTI), and restrictive patient selection criteria, there is significant unmet need for therapeutic agents that enable tissue survival and repair following acute ischemic damage for a broader population of stroke patients. In this preclinical study, we evaluated whether elezanumab, a human anti-RGMa monoclonal antibody, could improve neuromotor function and modulate neuroinflammatory cell activation following AIS with delayed intervention times up to 24 h using a rabbit embolic permanent middle cerebral artery occlusion model (pMCAO). In two replicate 28-day pMCAO studies, weekly intravenous infusions of elezanumab, over a range of doses and TTIs of 6 and 24 h after stroke, significantly improved neuromotor function in both pMCAO studies when first administered 6 h after stroke. All elezanumab treatment groups, including the 24 h TTI group, had significantly less neuroinflammation as assessed by microglial and astrocyte activation. The novel mechanism of action and potential for expanding TTI in human AIS make elezanumab distinct from current acute reperfusion therapies, and support evaluation in clinical trials of acute CNS damage to determine optimal dose and TTI in humans. A: Ramified/resting astrocytes and microglia in a normal, uninjured rabbit brain. B: Rabbit pMCAO brain illustrating lesion on right side of brain (red), surrounded by penumbra (pink) during acute phase post stroke, with minimal injury to left brain hemisphere. Penumbra characterized by activated astrocytes and microglia (region in crosshair within circle), with upregulation of free and bound RGMa. C: Elezanumab binds to both free and bound RGMa, preventing full activation of astrocytes and microglia. D: Elezanumab is efficacious in rabbit pMCAO with a 4 × larger TTI window vs. tPA (6 vs. 1.5 h, respectively). In human AIS, tPA is approved for a TTI of 3-4.5 h. Elezanumab is currently being evaluated in a clinical Ph2 study of AIS to determine the optimal dose and TTI (NCT04309474).

PMID:37326791 | DOI:10.1007/s12975-023-01164-2

Clin Pharmacol Ther. 2023 Jun 16. doi: 10.1002/cpt.2975. Online ahead of print.

ABSTRACT

Dipeptidyl peptidase-4 inhibitors (DPP-4i) interact with sulfonylureas to increase their risk of hypoglycemia. Our population-based study assessed whether intra-class pharmacologic heterogeneity among sulfonylureas (long- versus short-acting) and DPP-4i (peptidomimetic versus non-peptidomimetic) modifies this interaction. We conducted a cohort study using the UK’s Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data. We assembled a cohort of patients initiating sulfonylureas (2007-2020). Using a time-varying exposure definition, we assessed the risk of severe hypoglycemia (hospitalization with or death due to hypoglycemia) associated with 1) concomitant use of long-acting sulfonylureas (glimepiride, glibenclamide) with DPP-4i compared to concomitant use of short-acting sulfonylureas (gliclazide, glipizide) with DPP-4i; and 2) concomitant use of sulfonylureas with peptidomimetic DPP-4i (saxagliptin, vildagliptin) compared to concomitant use of sulfonylureas with non-peptidomimetic DPP-4i (sitagliptin, linagliptin, alogliptin). Time-dependent Cox models estimated confounder-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Our cohort included 196,138 sulfonylurea initiators. During a median follow-up of 6 years, 8,576 events of severe hypoglycemia occurred. Compared to concomitant use of short-acting sulfonylureas with DPP-4i, concomitant use of long-acting sulfonylureas with DPP-4i was not associated with the risk of severe hypoglycemia (adjusted HR, 0.87; 95% CI, 0.65-1.16). Compared to concomitant use of sulfonylureas with non-peptidomimetic DPP-4i, concomitant use of sulfonylureas with peptidomimetic DPP-4i was also not associated with the risk of severe hypoglycemia (HR, 0.96; 95% CI, 0.76-1.22). Intra-class pharmacologic heterogeneity did not modify the association between concomitant use of sulfonylureas (short- vs long-acting) and DPP-4i (peptidomimetic vs non-peptidomimetic) and the risk of severe hypoglycemia.

PMID:37326010 | DOI:10.1002/cpt.2975

J Periodontol. 2023 Jun 16. doi: 10.1002/JPER.23-0236. Online ahead of print.

ABSTRACT

BACKGROUND: Periodontal diseases can negatively impact the oral health related quality of life (OHRQoL) of pregnant women. This study investigates the association between maternal oral inflammatory load (OIL), sociodemographic characteristics, and the OHRQoL in postpartum women.

METHODS: In this cross-sectional study, breastfeeding mothers were recruited from St. Michael’s hospital, Toronto within 2-4 weeks postpartum. Mothers were categorized into “Normal/low” and “High” OIL groups based on the absolute counts of oral polymorphonuclear neutrophils (oPMNs). The Oral Health Impact Profile-14 questionnaire was used to assess the impact of the maternal OIL on the OHRQoL. Multiple linear regression analyses were performed to examine the association between maternal sociodemographic factors including age, marital status, education level, employment status, parity, and their OHRQoL.

RESULTS: Forty-seven mothers were included in this study. Mothers with high OIL reported higher impact on their OHRQoL (30%) than mothers with normal/low OIL (21%), but these differences were not statistically different. There was a negative relationship between the mother’s education level and the extent of impact of OHRQoL on the “physical pain” dimension (P<0.05), and between the mothers’ age and employment status and the “physical disability” dimension (P<0.05). A positive correlation was noted between multi-parity and the extent of impact of OHRQoL on the “physical disability” dimension (P = 0.009), and between the marital status and the “psychological disability” dimension (P<0.05).

CONCLUSION: This study highlighted the significant impact of sociodemographic characteristics on the OHRQoL of mothers, showcasing the importance of considering these factors when implementing targeted preventive dental care programs for mothers. This article is protected by copyright. All rights reserved.

PMID:37326008 | DOI:10.1002/JPER.23-0236

Physiother Res Int. 2023 Jun 16:e2028. doi: 10.1002/pri.2028. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Restricted dorsiflexion range of motion (DFROM) could impact dynamic balance in sports. This study aimed to investigate the relationship between dorsiflexion range of motion and the Y-Balance Test (YBT) in elite futsal players.

METHODS: Sixty-one asymptomatic male futsal players (mean age 26.57 (5.64) years, a mean body mass index of 25.40 (2.69) kg/m² ) were included. DFROM was measured by the weight-bearing lunge test (WBLT). DFROM data were obtained using smartphone-based motion capture. The Pearson correlation coefficient verified the correlation between the variables.

RESULTS: Dominant and nondominant leg ankle DFROM was significantly correlated with the anterior component of YBT (r = 0.27 and 0.51, respectively). The posteromedial component and the composite score of the YBT were also significantly correlated with nondominant leg ankle DFROM (r = 0.31 and 0.34, respectively)]. The other measures were not statistically significant. DFROM explained between 7% and 24% of the variation of the distances reached in the YBT.

CONCLUSION: Dorsiflexion range of motion measured by weight bearing lunge test is positively correlated with dynamic balance in futsal players.

PMID:37325995 | DOI:10.1002/pri.2028

Int J Technol Assess Health Care. 2023 Jun 16;39(1):e35. doi: 10.1017/S026646232300034X.

ABSTRACT

OBJECTIVE: To assess the clinical effectiveness of fluticasone furoate nasal spray (FFNS) versus placebo on nasal symptoms and safety in children with perennial allergic rhinitis (AR).

METHODS: A comprehensive review was conducted with data obtained from Medline and Embase databases up to April 2023. The population of interest was patients aged 2-12 years with perennial AR. The selection was limited to randomized controlled trials (RCTs), comparing FFNS with placebo. Outcomes of interest included the reflective total nasal symptoms scores (rTNSS) and safety. To assess the minimal clinically important difference for rTNSS, the Cohen’s guideline was used. If the pooled standardized mean difference (SMD) and the lower limit of the 95 percent confidence interval (CI) exceeded the threshold of -0.20, effects were considered clinically significant.

RESULTS: Three RCTs (959 pediatric patients) were selected. One study evaluated the short-term use of FFNS, another evaluated the long-term use of FFNS, and another evaluated both the short-term and long-term use of FFNS. FFNS produced a statistically significant reduction over placebo in rTNSS (SMD -0.18; 95 percent CI -0.35 to -0.01, p = 0.03) in long-term treatment studies, but not in short-term treatment studies. However, since the mean reduction did not reach the minimum clinically important difference (SMD -0.20), these results were considered clinically not relevant. Safety outcomes with FFNS were similar to placebo.

CONCLUSIONS: The currently available evidence suggests that FFNS, 110 μg once daily, compared to placebo, does not produce a meaningful clinical effect on nasal symptom in children with perennial AR.

PMID:37325979 | DOI:10.1017/S026646232300034X

Monaldi Arch Chest Dis. 2023 Jun 15. doi: 10.4081/monaldi.2023.2640. Online ahead of print.

ABSTRACT

Reflux asthma is an entity characterised by typical symptoms and in some cases is ‘silent’ and is more dangerous when associated with obesity and sleep apnoea syndrome. Its prevalence in the general population is high, as demonstrated by numerous studies listed below, and it is particularly a problem in the paediatric population; where, despite treatment by medical specialists, asthma symptoms are poorly controlled with a high risk of acute exacerbations. The aim of this clinical study is to show how the addition of a particular type of alginate (Deflux plus sachets) containing hyaluronic acid and melatonin at low doses administered over a prolonged period of six months, causes a reduction in vagal reflex stimulation of the oesophagus and pulmonary microaspiration reflexes by regulating lower oesophageal sphincter (LES) motility in asthmatic patients; improving the ACT score (asthma control test score). In the reported statistical analysis, ROC curves were performed for sensitivity and specificity for the analysed parameters, including the ACT score with statistically significant data p<0.0001. We conclude that the combination of conventional therapy for reflux asthma associated with alginates may improve the risk of acute asthma exacerbation and dynamic lung volumes.

PMID:37325973 | DOI:10.4081/monaldi.2023.2640

Vet Radiol Ultrasound. 2023 Jun 16. doi: 10.1111/vru.13265. Online ahead of print.

ABSTRACT

The size of an animal’s pelvis can have a substantial impact on the ease or difficulty of giving birth, which can vary depending on the breed. Radiography is a medical imaging technique that is commonly utilized in clinical cases to assess pelvic dimensions. The present retrospective, observational study was designed to evaluate pelvimetric differences in radiographic images of British Shorthair (BS) cats with dystocia and eutocia. Pelvimetric values (linear distance, angle, area, height/width) for ventrodorsal and laterolateral radiographic images were recorded in 15 BS cats with dystocia and 15 BS cats with eutocia. Statistical analysis of the obtained measurement values was performed. When the pelvimetric data were examined overall, it was seen that mean values, except the PL (pelvis length) measurement, were higher in cats with eutocia than in cats with dystocia. Vertical diameter, conjugate vera, coxal tuberosities, transversal diameter, acetabula, pelvic inclination, ischiatic arch, pelvis inlet area (PIA), and pelvic outlet area (POA) values were significantly higher in cats with eutocia than in cats with dystocia (P < 0.05). Mean PIA and POA measurement values in cats with dystocia were 22.89 ± 2.38 cm² and 19.59 ± 1.90 cm² , respectively; in cats with eutocia, the mean was calculated as 27.16 ± 2.76 cm² and 23.18 ± 1.88 cm² , respectively. In conclusion, the present study revealed that pelvimetric values, except the PL measurement, were higher in cats with eutocia than in cats with dystocia. Findings can be used to assist veterinarians in future clinical decision-making for pregnant BS cats.

PMID:37325948 | DOI:10.1111/vru.13265

Cancer Med. 2023 Jun 16. doi: 10.1002/cam4.6264. Online ahead of print.

ABSTRACT

BACKGROUND: Esophageal squamous cell cancer (ESCC) accounts for approximately 90% of esophageal cancer cases in China. There are no standard regimens for second or third-line chemotherapy of metastatic squamous esophageal cancer. The objective of this study was to investigate the security and effectiveness of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of ESCC.

METHODS: One hundred and twenty-eight patients with metastatic ESCC confirmed by histopathology were enrolled into this study. These patients had failure of the first-line chemotherapy combination of fluorouracil or platinum or paclitaxel and had not undergone chemotherapy with irinotecan or raltitrexed previously. Patients were randomly divided into irinotecan combined with raltitrexed group (experiment group) and irinotecan monotherapy group (control group). Overall survival (OS) and progression-free survival (PFS) were the primary endpoint.

RESULTS: In the control group, the median PFS (mPFS) and median OS (mOS) of patients were 3.37 and 5.3 months. In the experiment group, mPFS and mOS were 3.91 and 7.0 months. There was statistical significance of PFS and OS between two groups (PFS P = 0.002, OS P = 0.01). In subgroup analysis, in the second-line treatment, the mPFS of control and experiment group, was 3.90 and 4.60 months, mOS was 6.95 and 8.5 months, which was statistically significant differences between the two groups. (PFS P = 0.001, OS P = 0.005), In the third-line and beyond treatment, mPFS of control and experiment group was 2.80 and 3.19 months, mOS were 4.5 and 4.8 months. But there was no significant difference of PFS or OS between the two groups (PFS P = 0.19, OS P = 0.31). There was no statistical significance of toxicity side effects between two groups.

CONCLUSIONS: The PFS and OS of irinotecan plus raltitrexed may be better than that of irinotecan monotherapy, especially in second line treatment, which should be confirmed with a phase III study including much more patients.

PMID:37325938 | DOI:10.1002/cam4.6264

Stroke. 2023 Jun 16. doi: 10.1161/STROKEAHA.122.042290. Online ahead of print.

ABSTRACT

BACKGROUND: Subarachnoid hemorrhage (SAH) is characterized by acute and delayed reductions of cerebral blood flow (CBF) caused, among others, by spasms of cerebral arteries and arterioles. Recently, the inactivation of perivascular macrophages (PVM) has been demonstrated to improve neurological outcomes after experimental SAH, but the underlying mechanisms of protection remain unclear. The aim of our exploratory study was, therefore, to investigate the role of PVM in the formation of acute microvasospasms after experimental SAH.

METHODS: PVMs were depleted in 8- to 10-week-old male C57BL/6 mice (n=8/group) by intracerebroventricular application of clodronate-loaded liposomes and compared with mice with vehicle liposome injections. Seven days later, SAH was induced by filament perforation under continuous monitoring of CBF and intracranial pressure. Results were compared with sham-operated animals and animals who underwent SAH induction but no liposome injection (n=4/group each). Six hours after SAH induction or sham surgery, numbers of microvasospasms per volume of interest and % of affected pial and penetrating arterioles were examined in 9 standardized regions of interest per animal by in vivo 2-photon microscopy. Depletion of PVMs was proven by quantification of PVMs/mm³ identified by immunohistochemical staining for CD206 and Collagen IV. Statistical significance was tested with t tests for parametric data and Mann-Whitney U test for nonparametric data.

RESULTS: PVMs were located around pial and intraparenchymal arterioles and were effectively depleted by clodronate from 671±28 to 46±14 PVMs/mm³ (P<0.001). After SAH, microvasospasms was observed in pial arteries and penetrating and precapillary arterioles and were accompanied by an increase to 1405±142 PVMs/mm³. PVM depletion significantly reduced the number of microvasospasms from 9 IQR 5 to 3 IQR 3 (P<0.001).

CONCLUSIONS: Our results suggest that PVMs contribute to the formation of microvasospasms after experimental SAH.

PMID:37325921 | DOI:10.1161/STROKEAHA.122.042290