Comparing visual inspection methods for parenteral products in hospital pharmacy: between reliability, cost, and operator formation considerations.

INTRODUCTION: The COVID-19 pandemic has led to unforeseen and novel manifestations, as illustrated by the management of drug shortages through the development of hospital production of sterile pharmaceutical preparations (P2S). Visual inspection of P2S is a release control whose methods are described in monographs of the European Pharmacopoeia (2.9.20) and the United States Pharmacopeia (1790). However, these non-automated visual methods require training and proficiency testing of personnel. The main objective of this work was to compare the reliability and speed of analysis of two visual methods and an automated method for detecting visible particles by image analysis in P2S. Furthermore, these methods were used to evaluate sources of particulate contamination during pre-production processes (washing, disinfection, depyrogenation) and production (filling, capping). MATERIALS AND METHODS: Three pharmacy technicians examined 41 clear glass vials of type I, 10 and/or 50 mL through manual visual inspection (MVI), semi-automated (SAVI), and automated (AVI) inspection. The vials were distributed as follows: (i) 16 vials of water for injection containing either glass particles (224 µm or 600 µm), stopper fragments, or textile fibres; (ii) five sterile injectable specialties; (iii) 20 vials of water for injection prepared under different pre-production conditions. RESULTS AND DISCUSSION: MVI and SAVI detected 100% of visible particles compared with 28% for AVI, which showed a deficiency in detecting textile fibres. All three methods correctly analysed P2S that did not contain visible particles. The three methods detected particles in vials maintained under International Organization for Standardization (ISO) 9 pre-production conditions. However, detections by (i) MVI and SAVI, and by (ii) AVI of particles contained in vials maintained under ISO 8 pre-production conditions were deemed satisfactory and unsatisfactory, respectively. CONCLUSION: The importance of visual inspection of P2S requires rapid, sensitive, and reliable detection methods. In this context, MVI and SAVI have proven to be more effective than AVI for a more competitive financial, training, and implementation investment.

Socioeconomic burden and quality of life in meningioma patients.

PURPOSE: Long-term impairment of quality of life (QoL) occurs in a subset of meningioma patients, even after curative surgical resection. We sought to explore socioeconomic burden of meningioma surgery and associations with post-operative QoL to identify patients at risk for inferior outcome. METHODS: All patients with histological diagnosis of an intracranial meningioma treated at a single institution 2000-2013 were screened for inclusion in this cross-sectional survey study. Surveys comprised tools to assess socioeconomic status including social deprivation, QoL and symptom burden. Multivariate binary regression models controlling for established prognostic factors were applied to explore associations of socioeconomics with QoL 1 year after surgery. RESULTS: Completed surveys were returned by 249 patients. The median age at diagnosis was 56 years (SD ± 12), 185 patients (74%) were female and 219 (88%) had World Health Organization grade I meningiomas. One year after surgery, there was a 20% decrease in the number of patients working (p < 0.001), 22% of full-time working patients transitioned to part-time work (p < 0.001) and more patients depended on professional care (14% versus 4%, p < 0.001). Patients reported improved QoL, including improved global health (effect: 21%, 95% confidence interval [1] 15-26%), headaches (effect: 19%, CI 13-24%) and seizures (effect: 12%, CI 8-17%). On multivariable analyses, QoL after meningioma surgery was associated with preoperative employment status (odds ratio [OR] 0.41, 95% CI 0.17-0.98) and subjective work ability (OR 0.37, 95% CI 0.15-0.92). CONCLUSION: In a subset of meningioma patients, there is marked socioeconomic burden, which may be associated with inferior patient-reported outcome.

Soothing Effect of Pogostemon cablin Extract (Patchouli), via Cannabinoid Receptor 2 Modulation in Human Skin.

Skin functions as a neuro-immuno-endocrine tissue with well-defined neuronal networks and functions. The endocannabinoid system has been proven to be an important, homeostatic regulator for homeostatic and inflammatory events. The system comprises endogenous or exogenous ligands and receptors (CB1 and CB2). In the present study, we evaluated the soothing properties of a Pogostemon cablin (patchouli) extract. Agonist AM1241 and antagonist AM630 were used for CB2 receptor activation/inhibition. Expression of CB2 receptor and ß-endorphin was monitored by immunohistochemistry. Skin inflammation was induced with ultraviolet B (UVB) or lipopolysaccharide (LPS), and the following markers were used to highlight the anti-inflammatory properties of the extract: transient receptor potential vanilloid 1 (TRPV1), interleukin receptors 1 (IL1R1), and the interleukin 6 signal transducer (IL6ST). Our results demonstrated the implication of the CB2 receptor in the skin inflammation process. The expression of CB2 receptor and ß-endorphin was increased 48 hours after application of the extract. Furthermore, patchouli extract application helped to reduce IL1R1, IL6ST, and TRPV1 expression, in skin exposed to UVB or LPS. In conclusion, the application of the patchouli extract helps maintain skin integrity and reduce skin discomfort via modulation of CB2 receptor stimulation and the subsequent ß-endorphin release.

Post-operative cardiovascular complications and time to recurrence in meningioma patients treated with versus without pre-operative embolization: a retrospective cohort study of 741 patients.

PURPOSE: Preoperative embolization of radiographically suspected meningiomas is often performed to facilitate tumor resection. Its effects on the subsequent disease course of meningioma patients have not been studied in detail and randomized trials are lacking. The purpose of this study was to explore associations of preoperative meningioma embolization with postoperative outcome. PATIENTS AND METHODS: Patients undergoing resection of an intracranial meningioma at the University Hospital Zurich 2000-2013 (N = 741) were reviewed for the inclusion of pre-operative embolization in the management strategy. Annotations included demographics, radiographic, surgical, histological and hematological parameters, cardiovascular risk factors, pre- and postoperative neurological function and gene methylation-based classification. Binary regression and Cox proportional hazards models were applied to determine factors associated with outcome. RESULTS: Pre-operative embolization was performed in 337 patients (42%). Cardiovascular events after surgery comprised mostly deep vein thrombosis (N = 39) and pulmonary embolisms (N = 64). On multivariate analyses of post-operative cardiovascular adverse events controlling for established risk factors, there were associations with embolization (OR 2.38, 95% CI 1.37-4.00), and with female gender (OR 2.18, 95% CI 1.17-4.08). Recurrence-free survival (RFS) of embolized patients was less favorable among patients with WHO grade II or grade III meningiomas (median RFS: 4.3 vs. 7.0 years, P = 0.029) or in patients with intermediate or malignant gene methylation subtype meningiomas (median RFS: 2.0 vs. 8.2 years, P = 0.005). CONCLUSION: Pre-operative meningioma embolization may cause adverse outcomes. Randomized trials to determine benefit-risk ratios are warranted to clarify the role of pre-operative embolization for the treatment of meningioma patients.

Predicting outcome of epilepsy after meningioma resection.

BACKGROUND: Surgical excision is the standard treatment for intracranial meningiomas. Epilepsy is a major cause of morbidity in meningioma patients, but postoperative control of epilepsy is not achieved in a substantial fraction of patients. The purpose of this study was to define risk factors for postoperative epilepsy. METHODS: Patients treated for histologically confirmed intracranial meningioma at the University Hospital Zurich between 2000 and 2013 were retrospectively analyzed. Demographic, clinical, imaging, and electroencephalographic data were assessed. A binary regression model was applied to identify risk factors for postoperative epilepsy. RESULTS: Of the 779 patients analyzed, epileptic seizures occurred in 244 (31.3%) patients before surgery and in 204 (26.6%) patients after surgery. Of the 244 patients with preoperative epilepsy, 144 (59.0%) became seizure-free after surgery; of the 535 patients without preoperative seizures, 104 (19.4%) suffered from epilepsy after surgery. Risk factors for postoperative epilepsy were preoperative epilepsy (odds ratio [OR]: 3.46 [95% confidence interval {CI}: 2.32-5.16]), major surgical complications including CNS infections (OR: 5.89 [95% CI: 1.53-22.61]), hydrocephalus (OR: 3.27 [95% CI: 1.35-7.95]), recraniotomy (OR: 2.91 [95% CI: 1.25-6.78]), and symptomatic intracranial hemorrhage (OR: 2.60 [95% CI: 1.17-5.76]) as well as epileptiform EEG potentials (OR: 2.52 [95% CI: 1.36-4.67]), younger age (OR: 1.74 [(95% CI: 1.18-2.58]), and tumor progression (OR: 1.92 [95% CI: 1.16-3.18]). Postoperative improvement or recovery from preoperative neurologic deficits was associated with improved seizure control (OR: 0.46 [95% CI: 0.25-0.85], P = .013). CONCLUSION: We suggest prospective validation of a score ("STAMPE2") based on clinical findings, EEG, and brain-imaging measures to estimate postoperative seizure risk and guide anticonvulsant treatment in meningioma patients.