Effects of polyol and surfactant plasticisers on lyophilised rice starch wafers for buccal drug delivery.

Rice starch is a promising biopolymer for buccal formulations but typical oven drying may promote starch retrogradation that affects mechanical properties. Hence, lyophilisation was proposed here to improve starch product's stability. This study aims to investigate the effects of plasticisers (sorbitol and Tween® 80, T80) on the characteristics and drug release profiles of lyophilised rice starch wafers incorporated with propranolol hydrochloride. The wafers were prepared by lyophilising starch mixture (5%w/v) with plasticiser (0.2 and 0.3 g/g) and drug (10, 20, 30%w/w). Control wafers exhibited loose layers with rough wrinkled surface. Sorbitol resulted in a dense structure with higher puncture strength (PS) but lower water absorption capacity (WAC) while T80 loosened the flakes that reduced PS and increased WAC. Drug inclusion decreased PS and increased WAC of unplasticised wafers. T80-plasticised wafers with drug had a lower PS and higher WAC than sorbitol-plasticised wafers. Particularly, T80-plasticised wafers achieved outstandingly high PS and the lowest WAC at 30%w/w drug. Drug dissolution of wafers relied mainly on the drug crystallinity and WAC at 10 and 30%w/w drug. Plasticisers reduced and increased drug dissolution at 10 and 20%w/w drug, respectively. This study highlights the potential of lyophilisation in preparing rice starch wafers for buccal delivery.

Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample.

OBJECTIVES: We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea. METHODS: In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022. RESULTS: In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%. CONCLUSIONS: The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.

A Review of the Paravertebral Block: Benefits and Complications.

PURPOSE OF REVIEW: Paravertebral nerve blocks (PVB) have experienced a surge over the past 2 decades as improved access to ultrasound has increased ease of performance. The purpose of this review is to identify recent findings with regard to PVB's uses, including benefits, risks, and recommendations. RECENT FINDINGS: PVB is reported as an effective method of analgesia both in intraoperative and postoperative applications, with novel applications showing its potential to replace general anesthesia for certain procedures. The use of PVB as a method of analgesia postoperatively has shown lower opioid usage and faster PACU discharge, when compared to alternative approaches like the intercostal nerve block, erector spinae plane block, pectoralis II block, and patient-controlled analgesia. Thoracic epidural analgesia and a serratus anterior plane block are comparable to PVB and can be used as alternatives. The incidence of adverse events is consistently reported to be very low with few new risks being identified as the use of PVB expands. While there are worthwhile alternatives to PVB, it is an excellent option to consider, particularly for higher-risk patients. For patients undergoing thoracic or breast surgery, PVB can improve opioid usage and shorten the length of stay leading to an overall positive impact on patient recovery and satisfaction. More research is needed to further expand novel applications.

A Breast Cancer Survivor's Self-Controlled Case Report: Methylprednisolone Acetate Provided a Week Longer Analgesia Than Dexamethasone Sodium Phosphate via Thoracic Paravertebral Blockade.

Proper perioperative pain control with opioid-sparing techniques that extend into post-discharge arena is desirable yet hard to accomplish in breast cancer patients. We here reported a case where we took advantage of long-acting local anesthetics in conjunction with glucocorticoids of different hydrophilic/lipophilic properties and achieved prolonged analgesia for days after single administration thoracic paravertebral blockade. Further exploration into the potential effects of long-acting glucocorticoids in breast cancer patients through peripheral nerve blockage is warranted.

Retrospective analysis of patients with locally advanced or metastatic gastric cancer in Argentina.

AIM: To assess patient and disease characteristics, treatment patterns and associated costs in patients with locally advanced or metastatic gastric cancer in Argentina, in the public and private sectors. METHODS: A historic cohort of patients who had received first-line chemotherapy treatment (platinum analog and/or a fluoropyrimidine) and were followed-up for at least three months after the last administration of a first-line cytotoxic agent were eligible. Case-report forms were prepared based on medical records from four Argentinian hospitals. Estimates of treatment costs were also calculated using the unit costs of the participating hospitals. RESULTS: Of 101 patients, more than three quarters (79.2%) were male, 41.6% were diagnosed with metastatic stage IV disease (mean age, 57.7years), and 27.7 % had a smoking history. Before locally advanced or metastatic gastric cancer diagnosis, 42.4% of the patients had received total gastrectomy. Ninety-seven percent of the patients received a doublet or triplet therapy, of which epirubicin in combination with oxaliplatin and capecitabine was the most common treatment (38%), followed by capecitabine plus oxaliplatin (29%). Around 36% of the patients responded to first-line treatment (complete and partial response). Out of the 76.2% of the patients who followed a second-line treatment, 37.7% were still administered a platinum analog and/or fluoropyrimidine. During the reported follow-up period, 50% of the patients progressed, and 32.8% had stable disease. The best supportive care consisted mostly of outpatient visits after last-line therapy (16.8%), palliative radiotherapy (16.8%), and surgery (30.7%). We observed significant differences between public and private hospital costs. CONCLUSIONS: Understanding treatment patterns in patients with locally advanced or metastatic gastric cancer may help address unmet medical needs for better patient management and improvement of their clinical outcome in Argentina.

OBJETIVO: Describir las características clínicas, los patrones de tratamiento y los costos asociados en pacientes con cáncer gástrico localmente avanzado o metastásico en Argentina, en los sectores público y privado. MÉTODOS: Una cohorte histórica de pacientes que recibieron tratamiento de quimioterapia de primera línea (análogo de platino y/o una fluoropirimidina) y fueron seguidos durante al menos tres meses después de la última administración de un agente citotóxico de primera línea fueron elegibles. Se extrajeron los datos a través de un cuestionario estructurado a partir de los registros médicos de cuatro hospitales argentinos. Las estimaciones de los costos de tratamiento también se calcularon utilizando los costos unitarios de los hospitales participantes. RESULTADOS: Entre los 101 pacientes, más de tres cuartas partes (79,2%) eran hombres, 41,6% fueron diagnosticados con enfermedad metastásica en estadio IV, la edad media fue de 57,7 años y el 27,7% tenían antecedentes de tabaquismo. Antes del diagnóstico de cáncer gástrico metastásico, el 42,4% de los pacientes habían recibido gastrectomía total. El 97% de los pacientes recibió una terapia doble o triplete, de los cuales el tratamiento más frecuente fue la epirubicina en combinación con oxaliplatino y capecitabina (38%), seguida de capecitabina + oxaliplatino (29%). Alrededor del 36% de los pacientes respondieron al tratamiento de primera línea (respuesta completa y parcial). Del 76,2% de los pacientes que siguieron un tratamiento de segunda línea, al 37,7% todavía se les administró un análogo de platino y/o fluoropirimidina. Durante el período de seguimiento, el 50% de los pacientes progresó y el 32,8% tenía enfermedad estable. La terapia de apoyo consistió principalmente en visitas ambulatorias después de la última línea de quimioterapia (16,8%), radioterapia paliativa (16,8%) y cirugía (30,7%). Se observaron diferencias significativas entre los costos de los hospitales públicos y privado. CONCLUSIONES: Comprender los patrones de tratamiento en pacientes con cáncer gástrico localmente avanzado o metastásico puede ayudar a abordar las necesidades médicas no satisfechas para un mejor manejo del paciente y la mejora de sus resultados clínicos en Argentina.

Retrospective analysis of patients with advanced or metastatic gastric cancer in Colombia.

Aims: To assess patient and disease characteristics, treatment patterns, and associated costs in patients with advanced or metastatic gastric cancer (A/MGC) in Colombia, in both the public and private hospitals. Materials and methods: A total of 145 patients who had received first-line chemotherapy treatment (platinum analog and/or a fluoropyrimidine) and were followed for at least 3 months after the last administration of a first-line cytotoxic agent were eligible for inclusion. Case-report forms were elaborated based on the patients' medical records from three Colombian hospitals. Estimates of treatment costs were calculated using unit costs from the participating hospitals. Results: Of the 145 patients, more than half (64.83%) were male, 79.56% were diagnosed with metastatic stage IV disease (mean age = 58.14 years). Prior to MGC diagnosis, 31.71% of the patients being operated on received a total gastrectomy; 66.9% of the patients received a doublet therapy, of which 5-fluorouracil (5-FU) in combination with cisplatin was the standard treatment (14%), followed by combination with leucovorin (12%). Only around 10% of the patients responded to first-line treatment. Out of 41.38% of the patients who received a second-line treatment, 71.67% were still administered a platinum analog and/or fluoropyrimidine. During the follow-up period, 52% of the patients progressed and 20% achieved stable disease. Best supportive care mostly consisted of outpatient visits after last line-therapy (72.41%), palliative radiotherapy (18.6%), and surgery (37.2%). Limitations and conclusions: Gastric cancer is one of the main causes of cancer-related death in Colombia, as most of the patients are diagnosed at an advanced stage, when prognosis is poor. Treatment patterns are highly heterogeneous. Second-line treatments were mostly initiated with paclitaxel, capecitabine, irinotecan, or cisplatin.

Investigating detrusor muscle concentrations of oxybutynin after intravesical delivery in an ex vivo porcine model.

Intravesical oxybutynin is highly effective in the treatment of overactive bladder. Traditionally the mechanism of action was explained by antagonism of muscarinic receptors located in the detrusor, however evidence now suggests antimuscarinics may elicit their effect by modifying afferent pathways in the mucosal region. This study aimed to investigate the bladder wall distribution of oxybutynin in an ex vivo setting providing tissue - layer specific concentrations of drug achieved after intravesical delivery. Whole ex vivo porcine bladders were intravesically instilled with 0.167 mg mL(-1) oxybutynin solution. After 60 min, tissue samples were excised, serially sectioned parallel to the urothelial surface and extracted drug quantified. Drug distribution into the urothelium, lamina propria and detrusor was determined. Oxybutynin permeated into the bladder wall at a higher rate than other drugs previously investigated (apparent transurothelial Kp = 1.36 × 10(-5) cm s(-1) ). After 60 min intravesical instillation, concentrations achieved in the urothelium (298.69 µg g(-1) ) and lamina propria (43.65 µg g(-1) ) but not the detrusor (0.93 µg g(-1) ) were greater than reported IC50 values for oxybutynin. This work adds to the increasing body of evidence suggesting antimuscarinics elicit their effects via mechanisms other than direct inhibition of detrusor contraction.

Biweekly gemcitabine-paclitaxel, gemcitabine-carboplatin, or gemcitabine-cisplatin as first-line treatment in metastatic breast cancer after anthracycline failure: a phase II randomized selection trial.

BACKGROUND: The primary objective of this multicenter, open-label, randomized, parallel, phase II selection trial was to compare the objective tumor response to biweekly (every 2 weeks) gemcitabine/paclitaxel, gemcitabine/carboplatin, and gemcitabine/cisplatin as first-line treatment for metastatic breast cancer. PATIENTS AND METHODS: Eligible patients with stage IV disease who relapsed after anthracycline failure were randomly assigned in a 1:1:1 ratio to gemcitabine (2,500 mg/m2) plus paclitaxel 150 mg/m2 (n = 49); plus carboplatin, area under the curve = 2.5 mg/mL × min (n = 47); or plus cisplatin 50 mg/m2 (n = 51). Study therapy continued up until a maximum of 8 cycles and follow-up continued for 24 months. RESULTS: All patients were analyzed for efficacy and one patient was excluded from the safety analyses. The objective response was 26.5% [95% confidence interval (CI) 14.9-41.1] for gemcitabine/paclitaxel, 17.0% (95% CI 7.6-30.8) for gemcitabine/carboplatin, and 15.7% (95% CI 7.0-28.6) for gemcitabine/cisplatin. The adjusted odds ratio for tumor response was 0.33 (95% CI 0.10-1.06), P = 0.063 for gemcitabine/carboplatin versus gemcitabine/paclitaxel; 0.26 (95% CI 0.08-0.86), P = 0.027 for gemcitabine/cisplatin versus gemcitabine/paclitaxel; and 0.77 (95% CI 0.24-2.52), P = 0.671 for gemcitabine/cisplatin versus gemcitabine/carboplatin. There were no significant differences in overall survival or progression-free survival (P > 0.05). Grade 3 or 4 drug-related adverse events varied between groups and the majority of deaths (94.9%; 74/78) were related to disease progression. CONCLUSIONS: The gemcitabine-based treatments had comparable activity and tolerability. Similar survival characteristics and different toxicity profiles suggested that gemcitabine-platinum may be evaluated further in patients after anthracycline failure.

Altered energy dissipation ratio of the plantar soft tissues under the metatarsal heads in patients with type 2 diabetes mellitus: a pilot study.

BACKGROUND: Foot ulceration occurs frequently on the plantar aspect of the metatarsal head region, in which the altered foot biomechanics has been mentioned as a contributor. This study attempted to compare the energy dissipation in the plantar soft tissue under the metatarsal head between type 2 diabetic patients and age-matched healthy subjects in vivo. METHODS: The plantar soft tissues under the metatarsal heads in each left foot of 13 patients with type 2 diabetes mellitus and eight age-matched healthy subjects were measured with a loading-unloading device. The system comprised a 5-12 MHz linear-array ultrasound transducer and a load cell that operated at an impact velocity of about 5 cm/s. The stress-strain plot was derived by simultaneously recording the stress response and tissue deformation during a loading-unloading cycle. The energy dissipation ratio in all subjects could then be analyzed. FINDINGS: Although only the plantar soft tissue under the fourth metatarsal head in the diabetic patients endured significantly greater energy (P=0.035) than the healthy subjects, a trend of an increased energy dissipation ratio for the metatarsals in the diabetic patients was observed. INTERPRETATION: The plantar soft tissue under the metatarsal head in the diabetic patients endures high dissipated energy during a simulating walking status in the study. The increased dissipated energy in the tissue may be responsible for the tissue breakdown in the diabetic patients.

People with epilepsy are often perceived as violent.

This study explores the possibility that people with epilepsy are commonly and persistently perceived as potentially violent during and between seizures. In 1981 and again in 2006, we assessed responses to a questionnaire that includes vignettes and direct questions about violence in epilepsy. Groups sampled were medical and law students, physicians, child care workers, the general public, and people with epilepsy (n=271 in 1981 and n=388 in 2006). Nearly half of the respondents believed that violence was possible or likely during a seizure. Almost all groups answered at least 40% of questions incorrectly; the exception was physicians, who answered 20% incorrectly. Responses were fairly stable over the 25-year interval. Logistic regression revealed few predictors: older responders and physicians had more correct answers, whereas law students had poorer performance. These results indicate that fear of violence at the hands of people with epilepsy is prevalent and may contribute to stigma.

Tratamiento moderno de colectomía laparoscópica para lesiones malignas y benignas del colon / The modern treatment by laparoscopic colectomy for malignant and benign lesions of the colon

Objetivo: Demostrar la seguridad, eficacia, morbilidad, mortalidad y calidad de vida que ofrece la colectomía laparoscópica asistida en el tratamiento de la patología maligna y benigna del colon. Método: Se estudiaron 47 de 60 pacientes entre 25 y 83 años de edad sometidos a colectomía laparoscópica asistida en el periodo 1995 - 2005. Los pacientes fueron evaluados clínicamente y con exámenes de Eco-TAC ó resonancia magnética, colonoscopía y/o Rx. de colon, CEA para determinar el diagnóstico y estadiaje en caso de neoplasia. No se incluyeron pacientes con perforación colónica y peritonitis, ni tumores T4, ni mayores de 8 cms. Resultados: Las indicaciones fueron adenocarcinoma 27, diverticulitis crónica 17, adenoma velloso benigno 1, enfermedad de Crohn del íleon terminal con severa estenosis 1, poliposis familiar múltiple 1, vólvulo del ciego 1. 27 pacientes fueron del sexo femenino y 20 del sexo masculino con edades que fluctuaron entre 25 y 83 años. Las operaciones practicadas fueron colectomía derecha (12), colectomía izquierda (31), colectomía segmentaria (1), colectomía total (1), resección anterior (3). En los casos de neoplasia se completó con linfadenectomía en bloque. El tiempo operatorio osciló entre 5 horas en los casos iniciales y 3 horas en los últimos casos. El sangrado operatorio fue escaso x: 150 cc. (50-300 cc.). No se requirió de transfusiones de sangre. La eliminación de flatos se produjo en las primeras 24-36 horas en los operados del colon derecho y 24-56 horas en las del colon izquierdo. La patología mostró Dukes A, 2 pacientes (8 por ciento); Dukes B, 10 pacientes (37 por ciento); Dukes C, 15 pacientes (55 por ciento) en los casos de patología maligna. El número de ganglios extirpados fue de x: 20 (14-45). El tiempo de hospitalización fue de 4,5 días (2-6) para el colon derecho y 5.5 (3-9) para el colon izquierdo; en colectomía total 10 días por íleo prolongado y posterior control de diarrea. No hubo reoperaciones ni mortalidad. En los casos de cáncer de colon, el 60 por ciento recibió QT adyuvante. En el seguimiento no se ha documentado siembra peritoneal, recurrencia local ni recurrencia en los puertos de entrada. La sobrevida actuarial de los pacientes operados por cáncer es similar a la reportada de pacientes operados por técnica abierta y está directamente relacionada al grado de penetración en la pared del colon y al número de ganglios comprometidos...