Mechanisms of water permeation and diffusive API release from stearyl alcohol and glyceryl behenate modified release matrices.

This work aims to develop complimentary analytical tools for lipid formulation selection that offer insights into the mechanisms of in-vitro drug release for solid lipid modified release excipients. Such tools are envisioned to aide and expedite the time consuming process of formulation selection and development. Two pharmaceutically relevant solid lipid excipients are investigated, stearyl alcohol and glyceryl behenate, which are generally known to exhibit faster and slower relative release rates, respectively. Nuclear magnetic resonance spectroscopy and diffusometry are used, along with water uptake and dissolution experiments to help distinguish between two proposed in-vitro release mechanisms for crystalline caffeine from these matrices: 1) rate limiting movement of the wetting front through the particle, and 2) rate limiting diffusive release of the active from the wetted particle. Findings based on water permeation rates, API diffusion coefficients and kinetic modeling suggest that the rate limiting steps for caffeine release from these matrices are different, with stearyl alcohol being co-rate limited by movement of the wetting front and diffusive release of API, whereas glyceryl behenate is more strictly limited by diffusive release of API from the wetted matrix. A Peclet-like number is proposed to describe the different regimes of rate limitation for drug release. NMR spectroscopy and diffusometry are demonstrated to be useful tools for elucidating mechanisms of API release from crystalline drug/lipid mixtures and have significant potential value as screening tools in MR formulation development.

A novel architecture for achieving high drug loading in amorphous spray dried dispersion tablets.

Although Amorphous Solid Dispersions (ASDs) effectively increase bioavailability, tablet mass can be high due to the large fraction of excipients needed to stabilize the amorphous drug in the solid state, extend drug supersaturation in solution and achieve robust manufacturability. The aim of this work was to reduce tablet mass of an ASD tablet comprising a low glass transition temperature (Tg), rapidly crystallizing drug without compromising these key attributes. In this approach, erlotinib (Tg = 42 °C, Tm/Tg = 1.4 K/K) was spray dried with the high Tg polymer poly(methyl methacrylate-co-methacrylic acid) (Eudragit® L100, Evonik) (Tg = 187 °C) to facilitate high drug loading while maintaining physical stability. Hydroxypropyl methylcellulose acetate succinate (HPMCAS) (AQOAT® HF, Shin-Etsu) was granulated with the ASD to extend supersaturation in solution. For comparison, a benchmark ASD was spray dried at a lower drug loading with HPMCAS-H (Tg = 119 °C). This High Loaded Dosage Form (HLDF) approach reduced tablet mass by 40%, demonstrated similar physical stability and in vitro performance as the benchmark and exhibited excellent downstream manufacturability. Strategically combining two different polymers in a tablet to maintain physical stability and sustain supersaturation in solution can decrease tablet mass of some low Tg, rapidly crystallizing amorphous drugs.

Salmonella and Shiga Toxin-Producing Escherichia coli in Products Sampled in the Food Safety and Inspection Service Raw Pork Baseline Study.

The Food Safety and Inspection Service (FSIS) conducts microbiological baseline studies to determine national prevalence of select foodborne pathogens in federally inspected meat and poultry products and to obtain data for risk assessments. The FSIS conducted a baseline study from 1 June 2017 through 31 May 2018 to characterize and determine the prevalence of Salmonella and assess the occurrence of Shiga toxin-producing Escherichia coli (STEC) in a variety of raw pork products. In total, 4,014 samples from slaughter and processing establishments were analyzed for Salmonella; a subset of these samples (1,395) from slaughter establishments were also analyzed for STEC. Analyses determined that the national prevalence of Salmonella in raw pork products was highest in comminuted products (28.9%), followed by intact cuts (5.3%) and nonintact cuts (3.9%). Less than 1% of samples analyzed were positive for the top seven STEC. Our findings indicate there is a need for additional pathogen reduction strategies for raw pork products.

Postlaparotomy pain management: Comparison of patient-controlled analgesia pump alone, with subcutaneous bupivacaine infusion, or with injection of liposomal bupivacaine suspension.

OBJECTIVE: Efforts to achieve balance between effective pain management and opioid-related adverse events (ORAEs) have led to multimodal analgesia regimens. This study compared opioids delivered via patient-controlled analgesia (PCA) plus liposomal bupivacaine, a long-acting local anesthetic with potential to be an effective component of such regimens, to opioids delivered through PCA alone or PCA plus subcutaneous bupivacaine infusion (ONQ), following laparotomy. DESIGN: Prospective, randomized controlled trial. SETTING: Single, tertiary-care institution. PATIENTS: One hundred patients undergoing nonemergent laparotomy. INTERVENTIONS: Patients were randomly assigned to one of three study treatments: PCA only (PCAO), PCA with ONQ, or PCA with injectable liposomal bupivacaine suspension (EXP). MAIN OUTCOME MEASURES: Cumulative opioid use, daily mean patient-reported pain scores, and ORAEs through 72 hours postoperatively. RESULTS: On average, the EXP (n = 31) group exhibited less than 50 percent of the total opioid consumption of the PCAO (n = 36) group, and less than 60 percent of that for the ONQ (n = 33) group. Postoperative days 1 and 3 pain scores were significantly lower for the EXP group as compared to the ONQ and PCAO groups (p ≤ 0.005). Fewer patients in the EXP group (19.4 percent) experienced ORAEs compared to the PCAO (41.1 percent) and ONQ (45.5 percent) groups (p = 0.002). CONCLUSIONS: Laparotomy patients treated with liposomal bupivacaine as part of a multimodal regimen consumed less opioids, had lower pain scores, and had fewer ORAEs. The role of liposomal bupivacaine in the postoperative care of laparotomy patients merits further study.

Mediastinal Paraganglioma.

Paragangliomas of the mediastinum are rare, with only approximately 150 cases reported in the literature. Surgical excision is the treatment of choice; however, these tumors often lie near critical vascular structures. Here we present the case of a patient with a mediastinal paraganglioma discovered during a diagnostic procedure.

Paraphilias in adult psychiatric inpatients.

BACKGROUND: The goal of the present study was to examine the prevalence of paraphilias in an adult inpatient psychiatric population. METHODS: One hundred twelve consecutive, voluntarily admitted, adult male psychiatric inpatients were administered the Structured Clinical Interview for DSM-IV, Sexual Disorders Module, Male Version, to assess the rates of DSM-IV paraphilias. RESULTS: Fifteen patients (13.4%) reported symptoms consistent with at least one lifetime DSM-IV paraphilia. The most common paraphilias were voyeurism (n = 9 [8.0%]), exhibitionism (n = 6 [5.4%]), and sexual masochism (n = 3 [2.7%]). Patients who screened positive for a paraphilia had significantly more psychiatric hospitalizations (P = .006) and, on a trend level, were more likely to have attempted suicide. In addition, patients with paraphilias were significantly more likely to report having been sexually abused than patients without a paraphilia (P = <.001). Only 2 of the 15 paraphilic patients (13.3%) carried an admission diagnosis of a paraphilia. CONCLUSIONS: Paraphilias appear to be more common in adult male psychiatric inpatients than previously estimated. The study also demonstrated that these disorders were not screened for by the treating physician and thus may go untreated. Further, larger-scale studies are necessary in order to further examine the rates of these disorders in the general population.

Late-onset pathological gambling: clinical correlates and gender differences.

Age at illness onset has significant clinical implications for psychiatric disorders. Prior research has not systematically examined age at illness onset and its relationship to the clinical characteristics of pathological gambling (PG). Among a sample of 322 consecutive subjects with current DSM-IV PG, those with late-onset (at or after age 55 years) PG were compared to those with earlier onsets (at or prior to age 25, 26-54 years old) on measures of PG severity, co-occurring disorders, social and legal problems, and family history. Forty-two (13.4%) subjects reported onset of PG at or after age 55 years, 63 (19.6%) reported onset prior to age 25 years, and the majority (n=217; 67.4%) reported onset between the ages of 26 and 54 years. The late-onset group were less likely to declare bankruptcy (p=.029) or have credit card debt attributable to gambling (p=.006). Late-onset PG subjects were significantly more likely to have an anxiety disorder (p<.001) and significantly less likely to have a father (p=.025) or a mother (p=.048) with a gambling problem. Exploratory analyses identified an age-by-gender interaction with respect to treatment-seeking, with more pronounced age-related shortening in the duration between problem onset and treatment seeking observed in men. Age at onset of PG is associated with multiple important clinical features. Long durations of PG prior to treatment-seeking indicate the need for improved prevention efforts among individuals with early PG onset. Late-onset PG is relatively common and has distinct clinical characteristics suggesting that this population might benefit from unique prevention and treatment strategies.

Salmonella Enteritidis in meat, poultry, and pasteurized egg products regulated by the U.S. Food Safety and Inspection Service, 1998 through 2003.

The U.S. Food Safety and Inspection Service (FSIS) tests for Salmonella in meat, poultry, and egg products through three regulatory testing programs: the Pathogen Reduction-Hazard Analysis and Critical Control Point (PR-HACCP) program, the ready-to-eat program for meat and poultry products, and the pasteurized egg products program. From 1998 through 2003, 293,938 samples collected for these testing programs were analyzed for the presence of Salmonella enterica serotypes. Of these samples, 12,699 (4.3%) were positive for Salmonella, and 167 (1.3%) of the positive samples (0.06% of all samples) contained Salmonella Enteritidis. The highest incidence of Salmonella Enteritidis was observed in ground chicken PR-HACCP samples (8 of 1,722 samples, 0.46%), and the lowest was found in steer-heifer PR-HACCP samples (0 of 12,835 samples). Salmonella Enteritidis isolates were characterized by phage type, pulsed-field gel electrophoretic pattern, and antimicrobial susceptibility. Phage typing of 94 Salmonella Enteritidis isolates identified PT13 (39 isolates) and PT8 (36 isolates) as the most common types. One isolate from a ready-to-eat ham product was characterized as PT4. Electrophoretic analysis of 148 Salmonella Enteritidis isolates indicated genetic diversity among the isolates, with 28 unique XbaI electrophoretic patterns identified. Of these 148 isolates, 136 (92%) were susceptible to each of 16 antimicrobials tested. Two isolates were resistant to ampicillin alone, and 10 isolates were resistant to two or more antimicrobials. Isolation of Salmonella Enteritidis from FSIS-regulated products emphasizes the need for continued consumer education on proper food handling and cooking practices and continued work to decrease the prevalence of Salmonella in meat, poultry, and pasteurized egg products.