To examine opioid prescribing patterns after general surgery procedures and to estimate an ideal number of pills to prescribe.
Diversion of prescription opioids is a major contributor to the rising ...mortality from opioid overdoses. Data to inform surgeons on the optimal dose of opioids to prescribe after common general surgical procedures is lacking.
We evaluated 642 patients undergoing 5 outpatient procedures: partial mastectomy (PM), partial mastectomy with sentinel lymph node biopsy (PM SLNB), laparoscopic cholecystectomy (LC), laparoscopic inguinal hernia repair (LIH), and open inguinal hernia repair (IH). Postoperative opioid prescriptions and refill data were tabulated. A phone survey was conducted to determine the number of opioid pills taken.
There was a wide variation in the number of opioid pills prescribed to patients undergoing the same operation. The median number (and range) prescribed were: PM 20 (0-50), PM SLNB 20 (0-60), LC 30 (0-100), LIH 30 (15-70), and IH 30 (15-120). Only 28% of the prescribed pills were taken. This percentage varied by operation: PM 15%, PM SLNB 25%, LC 33%, LIH 15%, and IH 31%. Less than 2% of patients obtained refills.We identified the number of pills that would fully supply the opioid needs of 80% of patients undergoing each operation: PM 5, PM SLNB 10, LC 15, LIH 15, and IH 15. If this number were prescribed, the number of opioid initially prescribed would be 43% of the actual number prescribed.
There is wide variability in opioid prescriptions for common general surgery procedures. In many cases excess pills are prescribed. Using our ideal number, surgeons can adequately treat postoperative pain and markedly decrease the number of opioids prescribed.
The aim of this study was to determine whether an educational intervention was sufficient to decrease opioid prescribing after general surgical operations.
We recently analyzed opioid prescription ...and use for 5 common outpatient operations at our institution: partial mastectomy (PM), PM with sentinel lymph node biopsy (PM SLNB), laparoscopic cholecystectomy (LC), laparoscopic inguinal hernia repair (LIH), and open inguinal hernia repair (IH). We found that opioids were over-prescribed. We formulated guidelines for opioid prescribing that would halve the number of pills prescribed and also satisfy 80% of patients' opioid requirements.
We discussed our findings and opioid-prescribing guidelines with surgeons at our institution. We recommended that surgeons encourage patients to use a nonsteroidal anti-inflammatory drug (NSAID) and acetaminophen before using opioids. We then evaluated opioid prescriptions and use in 246 subsequent patients undergoing these same operations.
The mean number of opioid pills prescribed for each operation markedly decreased: PM 19.8 versus 5.1; PM SLNB 23.7 versus 9.6; LC 35.2 versus 19.4; LIH 33.8 versus 19.3, and IH 33.2 versus 18.3; all P < 0.0003. The total number of pills prescribed decreased by 53% when compared with the number that would have been prescribed before the educational intervention. Only 1 patient (0.4%) required a refill opioid prescription. Eighty-five percent of patients used either a NSAID or acetaminophen.
By defining postoperative opioid requirements through patient surveys and disseminating operation-specific guidelines for opioid prescribing to surgeons, we were able to decrease the number of opioids initially prescribed by more than half. Decreased initial opioid prescriptions did not result in increased opioid refill prescriptions.
We quantified concomitant medication polypharmacy, pharmacokinetic and pharmacodynamic interactions, adverse effects and adherence in Australian adults on effective antiretroviral therapy.
...Cross-sectional.
Patients recruited into a nationwide cohort and assessed for prevalence and type of concomitant medication (including polypharmacy, defined as ≥5 concomitant medications), pharmacokinetic or pharmacodynamic interactions, potential concomitant medication adverse effects and concomitant medication adherence. Factors associated with concomitant medication polypharmacy and with imperfect adherence were identified using multivariable logistic regression.
Of 522 participants, 392 (75%) took a concomitant medication (mostly cardiovascular, nonprescription or antidepressant). Overall, 280 participants (54%) had polypharmacy of concomitant medications and/or a drug interaction or contraindication. Polypharmacy was present in 122 (23%) and independently associated with clinical trial participation, renal impairment, major comorbidity, hospital/general practice-based HIV care (versus sexual health clinic) and benzodiazepine use. Seventeen participants (3%) took at least one concomitant medication contraindicated with their antiretroviral therapy, and 237 (45%) had at least one pharmacokinetic/pharmacodynamic interaction. Concomitant medication use was significantly associated with sleep disturbance and myalgia, and polypharmacy of concomitant medications with diarrhoea, fatigue, myalgia and peripheral neuropathy. Sixty participants (12%) reported imperfect concomitant medication adherence, independently associated with requiring financial support, foregoing necessities for financial reasons, good/very good self-reported general health and at least 1 bed day for illness in the previous 12 months.
In a resource-rich setting with universal healthcare access, the majority of this sample took a concomitant medication. Over half had at least one of concomitant medication polypharmacy, pharmacokinetic or pharmacodynamic interaction. Concomitant medication use was associated with several adverse clinical outcomes.
In 2014, UNAIDS outlined the 90-90-90 treatment targets. The "fourth 90" reflects the need to focus on optimising quality of life (HRQoL) in people living with HIV. Using a sample of non-heterosexual ...males in Melbourne, Australia, we aimed to assess HRQoL differences between HIV-positive and HIV-negative individuals, and identify factors that predict HRQoL both at baseline and after three years of follow up. Clinical information and patient-reported outcomes incorporating the Assessing Quality of Life-6D scale were collected at baseline and at three years. Sixty-two HIV-positive cases (antiretroviral therapy naïve at baseline) and 48 controls were enrolled. Results were compared between cases and controls at baseline, three-year follow-up, and between timepoints. HRQoL was significantly lower in cases compared to controls (83.5 (IQR 77.2-88.6) vs 87.3 (IQR 82.1-91.8), p = 0.022) at baseline, with increased depression and anxiety associated with reduced HRQoL in multivariate analysis. Mental health in cases improved between timepoints (75.0 (IQR 56.3-81.3) to 81.3 (IQR 62.5-81.3), p = 0.0428). No differences between the HRQoL of cases and controls were observed at three years. Increased mental health support may be required at commencement of antiretroviral therapy to enable similar levels of HRQoL between HIV-positive and HIV-negative individuals to be achieved.
Organisms typically face infection by diverse pathogens, and hosts are thought to have developed specific responses to each type of pathogen they encounter. The advent of transcriptomics now makes it ...possible to test this hypothesis and compare host gene expression responses to multiple pathogens at a genome-wide scale. Here, we performed a meta-analysis of multiple published and new transcriptomes using a newly developed bioinformatics approach that filters genes based on their expression profile across datasets. Thereby, we identified common and unique molecular responses of a model host species, the honey bee (Apis mellifera), to its major pathogens and parasites: the Microsporidia Nosema apis and Nosema ceranae, RNA viruses, and the ectoparasitic mite Varroa destructor, which transmits viruses.
We identified a common suite of genes and conserved molecular pathways that respond to all investigated pathogens, a result that suggests a commonality in response mechanisms to diverse pathogens. We found that genes differentially expressed after infection exhibit a higher evolutionary rate than non-differentially expressed genes. Using our new bioinformatics approach, we unveiled additional pathogen-specific responses of honey bees; we found that apoptosis appeared to be an important response following microsporidian infection, while genes from the immune signalling pathways, Toll and Imd, were differentially expressed after Varroa/virus infection. Finally, we applied our bioinformatics approach and generated a gene co-expression network to identify highly connected (hub) genes that may represent important mediators and regulators of anti-pathogen responses.
Our meta-analysis generated a comprehensive overview of the host metabolic and other biological processes that mediate interactions between insects and their pathogens. We identified key host genes and pathways that respond to phylogenetically diverse pathogens, representing an important source for future functional studies as well as offering new routes to identify or generate pathogen resilient honey bee stocks. The statistical and bioinformatics approaches that were developed for this study are broadly applicable to synthesize information across transcriptomic datasets. These approaches will likely have utility in addressing a variety of biological questions.
Chondroitinase ABC (ChABC) represents a promising therapeutic strategy for the treatment of spinal cord injury due to its potent effects on restoring function to spinal-injured adult mammals. ...However, there is limited mechanistic insight as to the underlying effects of ChABC treatment, where the effects are mediated, and which signaling pathways are involved in ChABC-mediated repair. Here we use a transgenic (YFP-H) mouse to demonstrate that cortical layer V projection neurons undergo severe atrophy 4 weeks after thoracic dorsal column injury and that ChABC is neuroprotective for these neurons after ICV infusion. ChABC also prevented cell atrophy after localized delivery to the spinal cord, suggesting a possible retrograde neuroprotective effect mediated at the injury site. Furthermore, neuroprotection of corticospinal cell somata coincided with increased axonal sprouting in the spinal cord. In addition, Western blot analysis of a number of kinases important in survival and growth signaling revealed a significant increase in phosphorylated ERK1 at the spinal injury site after in vivo ChABC treatment, indicating that activated ERK may play a role in downstream repair processes after ChABC treatment. Total forms of PKC and AKT were also elevated, indicating that modification of the glial scar by ChABC promotes long-lasting signaling changes at the lesion site. Thus, using the YFP-H mouse as a novel tool to study degenerative changes and repair after spinal cord injury we demonstrate, for the first time, that ChABC treatment regulates multiple signaling cascades at the injury site and exerts protective effects on axotomized corticospinal projection neurons.
We have developed a pyramidotomy model in mice to lesion the corticospinal tract at the level of the brainstem pyramidal tract, and evaluated the resultant impairments in motor function in a series ...of behavioural tests. Adult C57BL/6 mice received a unilateral pyramidotomy and a control group of mice underwent sham surgery. We studied the effects of this lesion on forepaw function using five behavioural paradigms, some of which have been widely used in rat studies but have not been fully explored in mice. The tests used were: a rearing test, which assesses forepaw use for weight support during spontaneous vertical exploration of a cylinder; a grid walking test, which assesses the ability to accurately place the forepaws during exploration of an elevated grid; a tape-removal test, which measures both sensory and motor function of the forepaw; a CatWalk automated gait analysis, which provides a number of quantitative measures including stride length and stride width during locomotion; and a staircase reaching task, which assesses skilled independent forepaw use. All tests revealed lesion effects on forepaw function with the tape removal, grid walking, rearing and CatWalk tests demonstrating robust effects throughout the testing period. The development of a pyramidotomy lesion model in mice, together with behavioural tests which can reliably measure functional impairments, will provide a valuable tool for assessing therapeutic strategies to promote regeneration and plasticity.