A comprehensive evaluation of online inhaler use techniques for obstructive airway disease.

BACKGROUND: Pulmonary inhaler therapy is a core treatment modality for >600 million individuals affected by obstructive airways disease globally. Poor inhaler technique is associated with reduced disease control and increased health care utilization; however, many patients rely on the internet as a technical resource. This study assesses the content and quality of online resources describing inhaler techniques. METHODS: A Google search was conducted in April 2023 capturing the top 5 search results for 12 common inhaler devices. Websites were compared to product monographs for preparation/first use, inhalational technique, and post-usage/device care. They were also assessed using accepted quality metrics (GQS, DISCERN, JAMA Benchmark scores) and clinically relevant aspects based on the literature and consensus statements. RESULTS: Websites regularly excluded critical steps important for proper inhaler technique. They performed best on information related directly to inhalation technique (average median score 78%), whereas steps related to preparation/first use (58%) or post-usage/device care (50%) were less frequently addressed. Median GQS, DISCERN, and JAMA Benchmark scores were 3 [IQR 3-4], 3 [IQR 2-4], and 1 [IQR 1-3], respectively. Clinically relevant factors were only addressed in about one-fifth of websites with no websites addressing smoking cessation, environmental considerations, or risk factors for poor technique. CONCLUSIONS: This study highlights gaps in online resources describing inhaler technique, particularly related to preparation/first use and post-usage/device care steps. Clinically relevant factors were rarely addressed across websites. Improvements in these areas could lead to enhanced inhaler technique and clinical outcomes.

Safety and Outcomes of the Off-Label Treatment of Intracranial Aneurysms with Pipeline Embolization Device: A Systematic Review and Meta-analysis.

BACKGROUND: Off-label use of pipeline embolization devices (PEDs) has been increasingly used for endovascular treatment of intracranial aneurysms. Numerous articles have highlighted the safety and effectiveness of PED placement from independent centers for both on- and off-label indications. There remains a paucity of information that considers overall safety and efficacy of off-label PED placement across the existing literature. Our objective is to systematically review the safety and occlusion outcomes of PED off-label use in intracranial aneurysm embolization. METHODS: A systematic search of PubMed and Embase was performed to identify studies on off-label use of PED. The selected studies provided relevant information, including study characteristics, patient demographics, clinical outcomes, peri-procedural complications, and long-term outcomes, which were subjected to meta-analysis. RESULTS: Twelve studies met the inclusion and exclusion criteria. There were 747 patients and 791 aneurysms included for analysis. Among the patient, 69.2% were female, with an age range of 16 to 80 years. The overall incidence rates for ischemic and hemorrhagic complications were 7% (95% CI: 4%-10%) and 2% (95% CI: 0%-4%), respectively. The mortality rate was 1% (95% CI: 0%-4%). The occlusion rates of aneurysm at initial follow up and 1 year follow-up were 82% (95% CI: 72%-91%) and 81% (95%CI: 75%-86%), respectively. Meta-regression analysis indicated no correlation between occlusion rate and factors such as age, sex, aneurysm size, location, morphology, rupture, or history of treatment. CONCLUSIONS: Despite variations in results observed in single-center studies, this meta-analysis provides evidence supporting the safety and efficacy of PED off-label use.

Adjuvant carboplatin and paclitaxel with "sandwich" method radiotherapy for stage III or IV endometrial cancer: long-term follow-up at a single-institution.

OBJECTIVE: To evaluate disease-free survival (DFS) and overall survival (OS) associated with adjuvant carboplatin and paclitaxel chemotherapy interposed with radiation for advanced endometrial cancer. METHODS: This is a cohort study of adult women with stage III or IV endometrial cancer treated at a single institution, between April 2002 and October 2017. Tumor and treatment characteristics were recorded. Treatment consisted of 4 cycles of intravenous paclitaxel and carboplatin every 3 weeks, followed by external beam radiotherapy to the pelvis (45-50 Gy), and another 2 cycles of chemotherapy. One cohort of patients were prospectively enrolled from 2002 through 2006 and an additional cohort from 2007 to 2017, which was retrospectively analyzed. Primary endpoints for this study were DFS and OS rates which were calculated using Cox regression models. RESULTS: Eighty-two patients with a median age of 66.5 years (range, 35-83 years) were included. Median follow-up was 46 months (range, 9-196 months). Most patients had stage IIIC disease (62.2%) and serous carcinoma histology (46.3%). Median OS was 146 months and median DFS was 71 months. A 5-year OS and DFS were 64.9% and 55.7%, respectively. Age >60 years subgroup was at a significantly higher risk of DFS event or death. Histological subtype, location of positive nodes, and cancer stage (IIIa vs. higher stage) did not correlate to a higher risk of recurrence or death. CONCLUSION: Long term follow-up and a larger population confirm that the chemoradiotherapy sandwich method yields favorable outcomes in patients with high-risk endometrial cancer.

A Rare Association of Mixed Autoimmune Hemolytic Anemia with Gastric Carcinoma.

This case report outlines a 70-year-old female patient who presented with a concurrent mixed autoimmune hemolytic anemia (AIHA) and a gastric adenocarcinoma. Her treatment course of these two diseases is summarized, which included supportive care, neoadjuvant chemotherapy for her gastric adenocarcinoma, steroids, rituximab, and surgical resection of the tumor. This approach ultimately led to the stabilization of her AIHA and primary cure for her solid malignancy. We briefly review both AIHA and gastric adenocarcinoma as clinical entities, propose working causes of hemolytic anemia including gastric adenocarcinoma, and outline a successful treatment pathway for these two concurrent conditions.

Effect of cerebrospinal fluid drainage on clinical outcomes following aneurysmal subarachnoid hemorrhage.

OBJECTIVES: We study the relationship between external ventricular drainage (EVD) of cerebrospinal fluid output and functional outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A retrospective chart review of patients presenting to a single center with aSAH was performed. The primary outcome was good functional outcomes assessed by a composite of the modified Rankin scale (mRS 0-2) at last follow-up. Secondary outcomes were clinical and radiographic vasospasm. For data analysis, multivariable generalized estimating equations adjusting for potential confounders were used. RESULTS: A total of 119 patients were included; 91 (75.6%) presented with a modified Fisher grade 4 and 76 (63.9%) had hydrocephalus. The median EVD duration was 13 days. On average, most EVDs were set at 15 cmH2O (50, 42%). Follow-up was available in 109 patients; median time was 10.7 months; 69 (63.3%) had good outcomes. Multivariable analysis showed that EVDs set at 10 cmH2O had increased odds of good outcomes for every ml increase in the EVD output (OR = 1.02; 95% CI 1.01-1.03; p = 0.001). Post estimation analyses show that EVDs at 10 cmH2O with output close to 200 ml predicted a 50% probability of good outcomes. CONCLUSIONS: Increased EVD outputs were associated with favorable outcomes at the last follow-up.

Experimental Cannabinoid 2 Receptor Activation by Phyto-Derived and Synthetic Cannabinoid Ligands in LPS-Induced Interstitial Cystitis in Mice.

Interstitial cystitis (IC) is a chronic bladder disorder with unclear etiology. The endocannabinoid system has been identified as a key regulator of immune function, with experimental evidence for the involvement of cannabinoid receptors in bladder inflammation. This study used intravital microscopy (IVM) and behavioral testing in lipopolysaccharide-induced IC, to investigate the anti-inflammatory analgesic effects of a natural dietary sesquiterpenoid, beta-caryophyllene (BCP), which is present in cannabis among other plants, and has reported agonist actions at the cannabinoid 2 receptor (CB2R). BCP's anti-inflammatory actions were compared to the synthetic CB2R-selective cannabinoid, HU308, and to an FDA-approved clinical treatment (dimethyl sulfoxide: DMSO). IVM data revealed that intravesical instillation of BCP and/or HU308 significantly reduces the number of adhering leukocytes in submucosal bladder venules and improves bladder capillary perfusion. The effects of BCP were found to be comparable to that of the selective CB2R synthetic cannabinoid, HU308, and superior to intravesical DMSO treatment. Oral treatment with BCP was also able to reduce bladder inflammation and significantly reduced mechanical allodynia in experimental IC. Based on our findings, we believe that CB2R activation may represent a viable therapeutic target for IC, and that drugs that activate CB2R, such as the generally regarded as safe (GRAS) dietary sesquiterpenoid, BCP, may serve as an adjunct and/or alternative treatment option for alleviating symptoms of inflammation and pain in the management of IC.

Monoacylglycerol lipase inhibition as potential treatment for interstitial cystitis.

Interstitial cystitis is a chronic inflammatory condition of the urinary bladder with an unclear etiology. Currently, there are no widely accepted long-term treatment options available for patients with IC, with the European Association of Urology (EAU, 2017 guidelines), American Urology Association (AUA, 2014 guidelines), and the Royal College of Obstetricians and Gynaecologists (RCOG, 2016 guidelines) all suggesting various different conservative, pharmacological, intravesical, and surgical interventions. The endocannabinoid system represents a potential target for IC treatment and management. Activation of cannabinoid receptor 2 (CBR2) with various agonists has previously been shown to reduce leukocyte differentiation and migration, in addition to inhibiting the release of pro-inflammatory cytokines at the site of inflammation. These receptors have been identified in the detrusor and sensory nerves of the urothelium in various mammalian species, including humans. We hypothesize that by inhibiting the enzymes responsible for the catabolism of endogenous cannabinoids locally, bladder concentrations of CBR2 agonists will increase, particularly 2-arachidonyl glycerol, resulting in a diminished inflammatory response.

Validation of a Predictive Scoring System for Ventriculoperitoneal Shunt Insertion After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Hydrocephalus is a frequently encountered complication in the context of aneurysmal subarachnoid hemorrhage (aSAH). Here, we performed an external validation of the recently proposed postsubarachnoid shunt scoring (PS3) system, which aims to stratify patients presenting with aSAH based on their relative risk of requiring ventriculoperitoneal (VP) shunt insertion. METHODS: A retrospective review of all patients presenting with aSAH to our institution between July 2007 and December 2016, who underwent computed tomography imaging at the time of hospital admission, was performed. RESULTS: A total of 242 patients (66.1% women) with aSAH were included in the analysis with a mean age of 55.6 years. Sixty-four (26.4%) patients had a Hunt and Hess grade of 4 or 5 on admission. An external ventricular drain (EVD) was placed in 130 (53.7%) patients during the hospital admission. EVD placement was found to correlate with an increased rate of VP shunt placement (P < 0.001), and a trend toward an association between a high Hunt and Hess grade and VP shunt placement was observed (P = 0.05). The area under the receiver operating characteristic curve for the PS3 system was found to be 0.845. The system reliably predicted shunt-dependent chronic hydrocephalus in our patient cohort (odds ratio, 3.36; 95% confidence interval, 2.31-4.89; P < 0.001). CONCLUSIONS: Data from this study validated the previously proposed PS3 system, which was found to more accurately predict shunt-dependent chronic hydrocephalus in patients with aSAH compared with other such systems in the neurosurgical literature, such as the chronic hydrocephalus ensuing from SAH score, Barrow Neurological Institute, and shunt dependency in aSAH systems.