Changes in Hydrocodone Misuse Exposures Reported to U.S. Poison Centers Following Rescheduling in 2014.

BACKGROUND: In 2014, the Drug Enforcement Administration rescheduled hydrocodone combination products to Schedule II to reduce nonmedical use and diversion. METHODS: The impact of rescheduling was assessed using quarterly data from 2011 through 2019 from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System Poison Center Program and IQVIATM Longitudinal Prescription Data. Trends and immediate changes in prescriptions dispensed and misuse exposures before and after rescheduling involving hydrocodone, oxycodone, and other Schedule II opioid analgesics were calculated using segmented regression. RESULTS: Hydrocodone prescriptions were stable pre-rescheduling, decreased by 2.7% (95% CI: -3.6%, -1.8%, p < 0.0001) per quarter post-rescheduling. Misuse exposures involving hydrocodone were decreasing by 3.2% (95% CI: -3.9%, -2.4%, p < 0.0001) per quarter pre-rescheduling and decreased by 4.9% (95% CI: -5.5%, -4.2%, p < 0.0001) post-rescheduling. Immediate decreases in hydrocodone prescriptions and misuse exposure rates in 2014Q4 compared to 2014Q3 were significant and different from oxycodone or other Schedule II opioids. Schedule II opioid analgesics prescriptions in aggregate were stable prior to rescheduling, decreased by 10.8% (95%CI: -14.0%, -7.6%, p < 0.0001) immediately after the rescheduling, and decreased by 2.3% per quarter (95% CI: -3.1%, -1.5%, p < 0.0001) subsequently. Misuse exposures involving these opioids were decreasing by 3.3% (95% CI: -4.1%, -2.5%, p < 0.0001) prior to rescheduling then by 2.8%, (95% CI: -3.4%, -2.2%, p < 0.0001) after rescheduling. The immediate change in misuse was not significant. CONCLUSIONS: Rescheduling corresponded with changes in hydrocodone prescribing and misuse not offset by increases in other Schedule II opioid analgesics. Misuse exposures for hydrocodone and comparators were decreasing prior to rescheduling with little change post-intervention.

Measuring prescription opioid misuse and its consequences.

AIMS: Prescription drug misuse in the USA increased during the 1990s to 2010. The epidemic stimulated the need new analytical strategies and techniques to understand the medications involved, user characteristics and other factors needed to address the epidemic. METHODS: A strategy of mosaic surveillance has evolved. Using real world evidence, the goal is to paint a more complete profile of a drug's real world misuse using triangulation-integrating results from multiple sources, where each approach has unrelated sources of bias. RESULTS: Research findings have been remarkably consistent across multiple data sources. The most commonly misused opioid medications: hydrocodone = oxycodone > methadone = buprenorphine = tramadol = fentanyl (prescription form) > morphine > hydromorphone = oxymorphone > tapentadol. This rank order is similar to the number of prescriptions dispensed for each product in the USA. In the USA, prescription opioid misuse started to decrease about 2011. Typically, multiple drugs are misused together, particularly in lethal cases. Immediate release formulations are more commonly misused than extended release formulations. The introduction of tamper resistant formulations to resist crushing were followed by a decrease in misuse of those products. CONCLUSIONS: The rapid expansion of opioid prescribing was accompanied by increasing misuse and mortality. Interventions such as prescription drug monitoring programmes, increased law enforcement and abuse deterrent formulations have been followed by decreases in misuse of most opioid analgesics.

XEN glaucoma treatment system in the management of refractory glaucomas: a short review on trial data and potential role in clinical practice.

The recent development of new devices that are significantly less invasive, collectively termed minimally invasive glaucoma surgery, offers new perspective of intraocular pressure reduction with less risk, short operating times, and rapid recovery. The aim of this work is to provide a panoramic review of the currently published clinical data to assess the potential role of XEN gel stent (Allergan PLC, Irvine, CA, USA) in the management of glaucoma, which is the only filtering minimally invasive glaucoma surgery device that allows the subconjunctival filtration. The ab interno placement of the XEN gel stent offers an alternative for lowering intraocular pressure in refractory glaucoma as a final step, and in patients intolerant to medical therapy as an early surgical approach with minimum conjunctival tissue disruption, restricted flow to avoid hypotony, and long-term safety.

Comparative Rates of Mortality and Serious Adverse Effects Among Commonly Prescribed Opioid Analgesics.

INTRODUCTION: The epidemic of prescription opioid overdose and mortality parallels the dispensing rates of prescription opioids, and the availability of increasingly potent opioid analgesics. OBJECTIVE: The common assumption that more potent opioid analgesics are associated with higher rates of adverse outcomes has not been adequately substantiated. We compared the rate of serious adverse events among commonly prescribed opioid analgesics of varying potency. METHODS: Serious adverse events (SAEs; defined as death, major medical effect, or hospitalization) resulting from exposure to tablets containing seven opioid analgesics (oxycodone, hydrocodone, morphine, hydromorphone, oxymorphone, tapentadol, and tramadol) captured by the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System Poison Center Program were evaluated from 2010 through 2016. Rates of SAEs were adjusted for availability through outpatient dispensing data and regressed on morphine milligram equivalents (MME). RESULTS: There were 19,480 cases of SAE during the 7-year study period. Hydrocodone and oxycodone contributed to 77% of SAE cases. Comparing rates of outcome by relative potency, a hierarchy was observed with hydromorphone (8.02 SAEs/100 kg) and tapentadol (0.27 SAE/100 kg) as the highest and lowest rates, reflecting a 30-fold difference among individual opioid products. SAE rate and potency were related linearly-SAEs increased 2.04 per 100 kg drug dispensed for each 1-unit rise in MME (p = 0.004). Linear regression of SAE/100 kg drug dispensed and drug potency identified that MME comprised 96% of the variation observed. In contrast, potency did not explain variation seen using other study denominators (prescriptions dispensed, dosage units dispensed, and the number of individuals filling a prescription). CONCLUSIONS AND RELEVANCE: Potency of a prescription opioid analgesic demonstrates a significant, highly positive linear relationship with exposures resulting in SAEs per 100 kg drug dispensed reported to poison centers. Potency should be carefully considered from both individual provider and public health perspectives.

Trends in abuse and misuse of prescription opioids among older adults.

BACKGROUND: Dramatic increases in the prescriptive use of opioid analgesics during the past two decades have been paralleled by alarming increases in rates of the abuse and intentional misuse of these drugs. We examined recent trends in the abuse and misuse and associated fatal outcomes among older adults (60+ years) and compared these to trends among younger adults (20-59 years). METHODS: Trend analysis using linear regression models was used to analyze 184,136 cases and 1149 deaths associated with abuse and misuse of the prescription opioids oxycodone, fentanyl, hydrocodone, morphine, oxymorphone, hydromorphone, methadone, buprenorphine, tramadol, and tapentadol that were reported to participating U.S. Poison Centers of the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS(®)) System between 2006-Q1 and 2013-Q4. RESULTS: Rates of abuse and misuse of prescription opioids were lower for older adults than for younger adults; however, mortality rates among the older ages followed an increasing linear trend (P < 0.0001) and surpassed rates for younger adults in 2012 and 2013. In contrast, mortality rates among younger adults rose and fell during the period, with recent rates trending downward (P = 0.0003 for quadratic trend). Sub-analysis revealed an increasing linear trend among older adults specifically for suicidal intent (P < 0.0001), whereas these rates increased and then decreased among younger adults (P < 0.0001 for quadratic trend). CONCLUSION: Recent linear increases in rates of death and use of prescription opioids with suicidal intent among older adults have important implications as the U.S. undergoes a rapid expansion of its elderly population.

Assessment of prescription opioid intentional exposures across the rural-urban continuum in the United States using both population and drug availability rates.

PURPOSE: Prescription opioid abuse and misuse are a serious problem in the U.S. today. Several studies have shown that the epidemic disproportionately affects rural areas. This paper uses three different rates to gain a more complete picture of opioid abuse in rural areas. METHODS: This study examines prescription opioid intentional exposures using opioid classes tracked in the RADARS(®) System Poison Center Program. Intentional exposure rates were calculated adjusting for population and unique recipients of dispensed drug (URDD). These rates were analyzed using time (quarter) and the proportion of a three-digit zip code residing in a rural area as covariates. Additionally, the URDD per population rate was calculated to examine the proportion of the population filling prescriptions for opioids. RESULTS: After adjusting for population, intentional exposure cases significantly increased as the proportion of the population residing in a rural area increased. However, when adjusting for URDD, intentional exposure cases decreased with increasing rural population. The URDD per population increased as the proportion of people residing in a rural area increased. CONCLUSIONS: Using both population and URDD adjusted intentional exposure rates gives a more complete picture of opioid abuse in rural areas. Considering product availability can be used to develop opioid abuse prevention strategies and further the education of physicians serving rural areas about this epidemic.

Using poison center exposure calls to predict prescription opioid abuse and misuse-related emergency department visits.

BACKGROUND: Prescription drug abuse is a critical problem in the USA and has been linked to more deaths than automobile accidents. Despite this growing epidemic, the USA lacks a timely early warning system. Poison centers (PCs) have the potential to act as sentinel reporting entities for prescription drug abuse and misuse due to near-real-time data reporting and abundant coverage in the USA. METHODS: Data from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System PC program were compared with data from the Drug Abuse Warning Network (DAWN) from 2004 through 2010. Population rates of PC call mentions regarding abuse and misuse of prescription opioids were compared with population rates of emergency department visit mentions of the same using linear regression. Products included in the analysis were the following: buprenorphine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, and oxycodone. RESULTS: The strength of association between RADARS System PC data and DAWN emergency department visits regarding all opioids in aggregate was strong (R² = 0.81, p < 0.001). The correlations between the two programs at the drug class level also were strong for buprenorphine, hydrocodone, hydromorphone, methadone, and oxycodone (all R² > 0.70, all p < 0.01), significant for fentanyl (p = 0.05), and moderate for morphine (p = 0.09). CONCLUSIONS: Data on prescription opioid drug abuse from the RADARS System PC program correlates well with emergency room data from DAWN. Due to timeliness of data, geographic coverage and strong associations with other warning systems, PC data can be used for sentinel reporting on prescription drug abuse and misuse in the USA.

Prevalence of clostridium difficile in excluded colons.

Clostridium difficile infection is associated with substantial morbidity and mortality, increased duration of hospitalization, and a marked economic impact. Several case reports and case series have described C. difficile infection in excluded bowels or immediately after reversal of defunctioning ileostomy. The aim of this prospective study is to detect whether the excluded colon is associated with a higher rate of C. difficile colonization than the normal population, which may increase the risk of C. difficile infection. Patients with defunctioning loop ileostomy, undergoing closure of ileostomy to restore bowel continuity, were prospectively recruited. Two stool samples were collected from the ileostomy effluent before closure of ileostomy and two after the procedure including the first bowel movement. All samples were cultured for C. difficile and analyzed for toxins A and B by a Premier EIA test. Demographic data and possible confounding factors were observed and recorded. Twenty-fine adult patients were recruited to this study; five patients were subsequently excluded. Two patients had positive stool cultures for C. difficile in the postoperative samples and another patient developed clinical pseudomembranous colitis with positive toxin. This indicates a possible colonization rate of 3 to 38 per cent (95% confidence interval). Four observed cases out of the 20 subjects taking part in this study would confidently conclude that C. difficile colonization in the excluded colon is 6 to 44 per cent, i.e., higher than the incidence in the healthy adult population, which is 3 per cent. However, the findings of this study prompt larger and well-powered studies to confirm these findings.

Patterns of cognitive impairments among heroin and cocaine users: the association with self-reported learning disabilities and infectious disease.

This study used data from six neuropsychological measures of executive function (EF) and general intellectual functioning (GIF) administered to 303 regular users of heroin and/or cocaine as indicators in a latent profile analysis (LPA). Results indicated the presence of three profiles: impaired GIF and EF profile (30.8%), intact GIF and EF profile (58.8%), and high GIF/intact EF profile (10.4%). Using a multinomial logistic regression, it was determined that individuals who reported being diagnosed with either a learning disability (LD) and/or attention-deficit/hyperactivity disorder (ADHD) were more likely to be in the impaired GIF and EF profile than other profiles. Results from a logistic regression indicated that the impaired GIF and EF profile was associated with a greater prevalence of past hepatitis B and/or C infection. Implication for harm reduction and treatment programs and the need to take into account individuals with LD and ADHD are discussed.

School achievement in 14-year-old youths prenatally exposed to marijuana.

The relation between prenatal marijuana exposure (PME) and school achievement was evaluated in a sample of 524 14-year-olds. Women were recruited during pregnancy and assessed, along with their offspring, at multiple phases from infancy to early adulthood. The sample represents a low-income population. Half of the adolescents are male and 55% are African American. School achievement was assessed with the Wechsler Individual Achievement Test (WIAT) Screener (Psychological Corporation, 1992). A significant negative relation was found between PME and 14-year WIAT composite and reading scores. The deficit in school achievement was mediated by the effects of PME on intelligence test performance at age 6, attention problems and depression symptoms at age 10, and early initiation of marijuana use. These findings suggest that the effects of PME on adolescent achievement are mediated by the earlier negative effects of PME on child characteristics. The negative impact of these characteristics on adolescent achievement may presage later problems in early adulthood.

Needlestick injuries during surgical procedures: a multidisciplinary online study.

BACKGROUND: Needlestick injuries are common during surgical procedures. Following such an injury, local protocols should be followed to minimize the risk of infection. AIMS: To identify who sustains such injuries, under what circumstances and what actions are taken to minimize the risk and in response to intraoperative needlestick injuries. METHODS: A questionnaire was submitted via e-mail to all staff in a National Health Service trust who took part in operations. The results were checked against occupational health department (OHD) records. RESULTS: One hundred and thirty-six of 255 appropriate responders completed the questionnaire (53%). Fifteen of 31 consultants (48%), 12/36 junior doctors (33%), 0/39 midwives (0%) and 8/30 theatre staff (27%) reported having had at least one intraoperative needlestick injury over the past year. Awareness of local protocols was significantly worse in the junior doctor group. Ninety-three percent of consultants, 67% of junior doctors and 13% of theatre staff did not comply with local protocols. The length of time it takes to do so (48%) and a perceived low infection risk of the patient (78%) were the commonest reasons for this. Hand dominance, role during surgery and double gloving were not significant risk factors; however, rare use of a no-touch technique was. Comparison with OHD records suggested that a maximum of 16% of intraoperative needlestick injuries were dealt with in accordance to local policy. CONCLUSIONS: Non-compliance with needlestick injury protocols is commonest among senior surgical staff. A revision of the protocol to reduce the time it takes to complete it may improve compliance.

Radical subtotal pancreatic resection, including splenectomy, is an effective one-off treatment for infected pancreatic necrosis.

BACKGROUND: Pancreatic resection for severe acute necrotizing pancreatitis has been associated with prohibitive mortality rates and has been hence replaced by piecemeal debridement, either by the open or the laparoscopic technique. We report the results of deliberate subtotal pancreatectomy with splenectomy for infected pancreatic necrosis. MATERIALS AND METHODS: Six-year prospective audit of patients treated by a single surgeon, with an interest in pancreatic disease, within a Low Volume Hospital (LVH) setting. Results are presented as median (IQR). RESULTS: During the study period 18 patients (9 males) with complicated severe acute pancreatitis underwent radical pancreatic resection. The median age was 61 years (range 36-69). The median time to operation after presentation was 27 days (range 2-74). Microbiological culture confirmed infection in 14 (78%) patients. Three patients (17%) died within 30 days of operation. Twelve of the 15 survivors (80%) underwent a single operative procedure. Three patients required a further laparotomy, of whom 2 required colectomy for ischemia. Median hospital and ICU stays were 43 (range 30-57) and 5 (range 4-6) days respectively. Six patients (40% of survivors) developed an infection of the left half of the chevron incision; however, all wounds were fully healed within 3 months. Long-term follow-up of survivors (n=14) revealed 8 (57%) to need at least occasional pancreatic enzyme supplementation and 5 (36%) to have diabetes mellitus. Two patients (14%) developed an incisional hernia. CONCLUSIONS: Radical resection of pancreas and spleen, combined with postoperative irrigation, was associated with comparatively low rates of morbidity and mortality for patients with infected pancreatic necrosis in a LVH setting.

A randomized, double-blind trial of the effect of metronidazole on pain after closed hemorrhoidectomy.

PURPOSE: Patients consider hemorrhoidectomy to be a painful operation. Attempts to reduce the length of inpatient stay have concentrated mainly on a reduction in postoperative pain. Metronidazole has been shown to reduce pain after open hemorrhoidectomy. The aim of this study was to evaluate the effect of metronidazole after closed hemorrhoidectomy. METHODS: Thirty-eight patients undergoing closed hemorrhoidectomy were randomly allocated to receive metronidazole 400 mg (n = 18) or placebo (n = 20) three times daily for seven postoperative days. All patients received a stool softener and analgesics perioperatively. Linear analog scales were used to assess expected pain, actual pain and patient satisfaction. Time to first bowel movement, return to normal activity, complications, and use of additional analgesics were recorded. RESULTS: Both groups of patients experienced less pain than expected. Patients in the metronidazole group required fewer additional analgesics postoperatively (6.3 vs. 26.3 percent), and satisfaction scores in the placebo group were higher at one week (0.5 vs. 2.5), although these differences were not statistically significant. There were no differences in pain actually experienced, time to first bowel movement, return to normal activity, or complications between the two groups. Satisfaction scores at six weeks for all patients were relatively high, with no significant difference between the groups. CONCLUSION: Closed hemorrhoidectomy results in high patient satisfaction and low pain scores. The use of postoperative metronidazole did not reduce postoperative pain.

Role of resting pressure gradient in the investigation of idiopathic fecal incontinence.

PURPOSE: One-third of patients who suffer from idiopathic fecal incontinence are found to have maximum mean resting pressures within the normal range. The objective of this study was to determine whether measuring the gradient of pressure at rest throughout the anal canal is a more sensitive predictor of incontinence in these patients. METHODS: Anorectal physiology measurements were retrospectively reviewed in patients referred over an 18-month period. Two patient groups were selected for the study: Group 1, continent patients (n = 80); and Group 2, patients with idiopathic fecal incontinence (n = 47). Maximum resting pressures, vector volumes, and resting pressure gradients were all contrasted, sensitivities and specificities were calculated, and receiver operating characteristic curve analyses were performed. Reproducibility studies were also performed for the calculation of the pressure gradient. RESULTS: Patient demographics were similar in the two groups. The resting pressure gradient, maximum mean resting pressure, and vector volumes were significantly lower in incontinent patients compared with the normal patients (P < 0.0001, all comparisons). The sensitivity (and specificity) of resting pressure gradient, maximum mean resting pressure, and vector volumes were 89 percent (96 percent), 55 percent (98 percent), and 53 percent (88 percent), respectively. CONCLUSION: The resting pressure gradient is the most accurate in detecting fecal incontinence. The authors conclude that this test is simple, reproducible, and identifies an abnormality in the majority of patients with idiopathic fecal incontinence.