Chronic-pharma: New Platform for Chronic Patients Pharmacotherapy Optimization

Over half of hospital revenue results from perioperative patient care, thus emphasizing the importance of efficient resource utilization within a hospital’s suite of operating rooms (ORs). Predicting surgical case duration, including Anesthesia-controlled time (ACT) and Surgical-controlled time (SCT) has been significantly detailed throughout the literature as a means to help manage and predict OR scheduling. However, this information has previously been divided by surgical specialty, and only limited benchmarking data regarding ACT and SCT exists. We hypothesized that advancing the granularity of the ACT and SCT from surgical specialty to specific Current Procedural Terminology (CPT^®) codes will produce data that is more accurate, less variable, and therefore more useful for OR schedule modeling and management. This single center study was conducted using times from surgeries performed at the University of Colorado Hospital (UCH) between September 2018 – September 2019. Individual cases were categorized by surgical specialty based on the specialty of the primary attending surgeon and CPT codes were compiled from billing data. Times were calculated as defined by the American Association of Clinical Directors. I² values were calculated to assess heterogeneity of mean ACT and SCT times while Levene’s test was utilized to assess heterogeneity of ACT and SCT variances. Statistical analyses for both ACT and SCT were calculated using JMP Statistical Discovery Software from SAS (Cary, NC) and R v3.6.3 (Vienna, Austria). All surgical cases (n?=?87,537) performed at UCH from September 2018 to September 2019 were evaluated and 30,091 cases were included in the final analysis. All surgical subspecialties, with the exception of Podiatry, showed significant variability in ACT and SCT values between CPT codes within each surgical specialty. Furthermore, the variances of ACT and SCT values were also highly variable between CPT codes within each surgical specialty. Finally, benchmarking values of mean ACT and SCT with corresponding standard deviations are provided. Because each mean ACT and SCT value varies significantly between different CPT codes within a surgical specialty, using this granularity of data will likely enable improved accuracy in surgical schedule modeling compared to using mean ACT and SCT values for each surgical specialty as a whole. Furthermore, because there was significant variability of ACT and SCT variances between CPT codes, incorporating variance into surgical schedule modeling may also improve accuracy. Future investigations should include real-time simulations, logistical modeling, and labor utilization analyses as well as validation of benchmarking times in private practice settings.

     

Massive intracardiac metastases secondary to squamous cell carcinoma located at the level of the penis

Penile cancer is an uncommon malignancy in the Developed World. They are dispersed mainly via the lymphatic pathway. We present a single case of massive intracardiac metastases secondary to epidermoid carcinoma of the penis. This is an extremely rare entity which has scarcely been documented.     

A 28-day oral dose toxicity study enhanced to detect endocrine effects of a purified technical pentabromodiphenyl ether (pentaBDE) mixture in Wistar rats

A 28-day subacute oral toxicity study was performed in Wistar rats with a purified preparation of the commercial pentabromodiphenyl ether (pentaBDE), DE-71. The applied OECD407 protocol was enhanced for endocrine and immune parameters, and to enable benchmark dose analysis. A vehicle control group and 7 dose groups were included, which received 0.27, 0.82, 2.47, 7.4, 22.2, 66.7 or 200 mg pentaBDE/kg bw/d (mkd). The liver appeared to be a key target organ, showing a marked increase of weight and centrilobular hepatocellular hypertrophy, probably due to the observed induction of P450 enzymes, notably CYP1A and CYP2B. A marked decrease of circulating total thyroxine (TT4) and an increase of plasma cholesterol were probably secondary to the liver effects. Furthermore, dose-dependently decreased weight of epididymis, seminal vesicles, and prostate, as well as sperm head deformities in males, and induction of CYP17 activity in adrenals in females were observed, all possibly related to anti-androgenic activity. Finally, we observed a substantial increase of large unstained cells in the blood and a decrease of apolar retinoids in the liver. All these effects had benchmark doses at the lower confidence bound (BMDL) in the low- or mid-dose range, but particular sensitive, potentially adverse effects were TT4 decrease (BMDLs 1.1 in males and 1.8 mkd in females), and decrease of hepatic apolar retinoids (BMDLs 0.5 mkd in males and 2.3 mkd in females). These results contribute to refinement of the hazard identification of pentaBDE and improved risk assessment of human exposure to this industrial chemical and environmental pollutant.     

A 28-day oral dose toxicity study in Wistar rats enhanced to detect endocrine effects of decabromodiphenyl ether (decaBDE)

Decabromodiphenyl ether (decaBDE) is a widely used brominated flame retardant, considered to be of low toxicity. However, previous toxicity studies applied exposure methods with low bioavailability of this compound, and the actual hazard of decaBDE for humans, which are environmentally exposed to decaBDE, may thus be underestimated in current risk assessments. The present 28 days oral toxicity study in Wistar rats was designed to facilitate detection of endocrine and immune modulating effects of decaBDE using an exposure protocol with improved bioavailability. A technical preparation of high purity decaBDE was thus tested by daily exposure through gavage with an emulsion of soy phospholipon/lutrol as a carrier. Most sensitive effect in males were increased weight of seminal vesicle/coagulation gland with BMDL of 0.2mg/kg bw/day and increased expression of hepatic CYP1A and CYP2B (BMDLs 0.5-0.7 mg/kg bw/day). In females the most sensitive effect was decreased activity of P450c17 (CYP17), which is a key enzyme in the androgen synthesis pathway, in adrenals (BMDL 0.18 mg/kg bw/day). These results suggest that decaBDE may represent an as yet unreported hazard for reproductive health.     

Subgrouping patients with fibromyalgia according to the results of the fibromyalgia impact questionnaire: a replication study

Fibromyalgia is a complex and heterogeneous disease, and several attempts have been made in order to identify different subgroups of patients sharing a common symptomatology. The purpose of the present study has been to replicate a subgroup classification proposed by de Souza et al. based in the Fibromyalgia Impact Questionnaire (FIQ) in a large sample of patients with a cultural and clinical setting different from the original one. Four hundred twenty-one patients were classified, according to the results of the visual analog FIQ subscales in type I o type II subgroups. Demographic and clinical data, as well as results of scales assessing disease’s severity, quality of life, sleep quality, anxiety and depression, were compared between the two groups. The profiles of type I and type II patients from our sample strikingly paralleled those of the original study, demonstrating the reproducibility of the classification. In our sample, 18.8% of the patients appertained to type I subgroup and 81.2% to type II subgroup. Patients from this later subgroup had higher comorbidity and received more drugs than those of the former. They were also more physically ill, with higher FIQ total scores and worse sleep quality, and more psychologically distressed, with higher levels of anxiety and depression and lower scores in the mental component summary of the Short-Form Health Questionnaire (SF-12). Our study shows that the proposed fibromyalgia classification is reliable and easy to perform and could be applied in further studies.     

The UDP N-acetylgalactosamine 4-epimerase gene is essential for mesophilic Aeromonas hydrophila serotype O34 virulence

Mesophilic Aeromonas hydrophila strains of serotype O34 typically express smooth lipopolysaccharide (LPS) on their surface. A single mutation in the gene that codes for UDP N-acetylgalactosamine 4-epimerase (gne) confers the O(-) phenotype (LPS without O-antigen molecules) on a strain in serotypes O18 and O34, but not in serotypes O1 and O2. The gne gene is present in all the mesophilic Aeromonas strains tested. No changes were observed for the LPS core in a gne mutant from A. hydrophila strain AH-3 (serotype O34). O34 antigen LPS contains N-acetylgalactosamine, while no such sugar residue forms part of the LPS core from A. hydrophila AH-3. Some of the pathogenic features of A. hydrophila AH-3 gne mutants are drastically reduced (serum resistance or adhesion to Hep-2 cells), and the gne mutants are less virulent for fish and mice compared to the wild-type strain. Strain AH-3, like other mesophilic Aeromonas strains, possess two kinds of flagella, and the absence of O34 antigen molecules by gne mutation in this strain reduced motility without any effect on the biogenesis of both polar and lateral flagella. The reintroduction of the single wild-type gne gene in the corresponding mutants completely restored the wild-type phenotype (presence of smooth LPS) independently of the O wild-type serotype, restored the virulence of the wild-type strain, and restored motility (either swimming or swarming).     

Reassessment of Genotype 1 Hepatitis C Virus Subtype Misclassification by LiPA 2.0: Implications for Direct-Acting Antiviral Treatment

The accuracy of LiPA 2.0 for hepatitis C virus 1 (HCV-1) subtype classification was analyzed. LiPA 2.0 genotype results from 101 HCV-1-infected patients were compared to genotype findings determined by direct core sequencing. Eleven (11%) samples were misclassified. Given the influence of the HCV-1-subtype in the anti-HCV therapy response, an alternative classification method is warranted.