Risks and benefits of oral modified-release compared with oral immediate-release opioid use after surgery: a systematic review and meta-analysis.

Prescription of modified-release opioids for acute postoperative pain is widespread despite evidence to show their use may be associated with an increased risk of adverse effects. This systematic review and meta-analysis aimed to examine the available evidence on the safety and efficacy of modified-release, compared with immediate-release, oral opioids for postoperative pain in adults. We searched five electronic databases from 1 January 2003 to 1 January 2023. Published randomised clinical trials and observational studies on adults who underwent surgery which compared those who received oral modified-release opioids postoperatively with those receiving oral immediate-release opioids were included. Two reviewers independently extracted data on the primary outcomes of safety (incidence of adverse events) and efficacy (pain intensity, analgesic and opioid use, and physical function) and secondary outcomes (length of hospital stay, hospital readmission, psychological function, costs, and quality of life) up to 12 months postoperatively. Of the eight articles included, five were randomised clinical trials and three were observational studies. The overall quality of evidence was low. Modified-release opioid use was associated with a higher incidence of adverse events (n = 645, odds ratio (95%CI) 2.76 (1.52-5.04)) and worse pain (n = 550, standardised mean difference (95%CI) 0.2 (0.04-0.37)) compared with immediate-release opioid use following surgery. Our narrative synthesis concluded that modified-release opioids showed no superiority over immediate-release opioids for analgesic consumption, length of hospital stay, hospital readmissions or physical function after surgery. One study showed that modified-release opioid use is associated with higher rates of persistent postoperative opioid use compared with immediate-release opioid use. None of the included studies reported on psychological function, costs or quality of life.

Impact of modified-release opioid use on clinical outcomes following total hip and knee arthroplasty: a propensity score-matched cohort study.

Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3-13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.

Effect of discharge opioid on persistent postoperative opioid use: a retrospective cohort study comparing tapentadol with oxycodone.

Opioid harm can vary by opioid type. This observational study examined the effect of opioid type (oxycodone vs. tapentadol) on rates of persistent postoperative opioid use ('persistence'). We linked hospital and community pharmacy data for surgical patients who were dispensed discharge opioids between 1 January 2016 and 30 September 2021. Patients were grouped by opioid experience ('opioid-naive' having received no opioids in the 3 months before discharge) and formulation of discharge opioid (immediate release only or modified release ± immediate release). Mixed-effects logistic regression models predicted persistence (continued use of any opioid at 90 days after discharge), controlling for key persistence risk factors. Of the 122,836 patients, 2.31% opioid-naive and 27.24% opioid-experienced patients met the criteria for persistence. For opioid-naive patients receiving immediate release opioids, there was no significant effect of opioid type. Tapentadol modified release was associated with significantly lower odds of persistence compared with oxycodone modified release, OR (95%CI) 0.81 (0.69-0.94) for opioid-naive patients and 0.81 (0.71-0.93) for opioid-experienced patients. Among patients who underwent orthopaedic surgery (n = 19,832), regardless of opioid experience or opioid formulation, the odds of persistence were significantly lower for those who received tapentadol compared with oxycodone. This was one of the largest and most extensive studies of persistent postoperative opioid use, and the first that specifically examined persistence with tapentadol. There appeared to be lower odds of persistence for tapentadol compared with oxycodone among key subgroups, including patients prescribed modified release opioids and those undergoing orthopaedic surgery.

Experimental verification of principal losses in a regulatory particulate matter emissions sampling system for aircraft turbine engines.

A sampling system for measuring emissions of nonvolatile particulate matter (nvPM) from aircraft gas turbine engines has been developed to replace the use of smoke number and is used for international regulatory purposes. This sampling system can be up to 35 m in length. The sampling system length in addition to the volatile particle remover (VPR) and other sampling system components lead to substantial particle losses, which are a function of the particle size distribution, ranging from 50 to 90% for particle number concentrations and 10-50% for particle mass concentrations. The particle size distribution is dependent on engine technology, operating point, and fuel composition. Any nvPM emissions measurement bias caused by the sampling system will lead to unrepresentative emissions measurements which limit the method as a universal metric. Hence, a method to estimate size dependent sampling system losses using the system parameters and the measured mass and number concentrations was also developed (SAE 2017; SAE 2019). An assessment of the particle losses in two principal components used in ARP6481 (SAE 2019) was conducted during the VAriable Response In Aircraft nvPM Testing (VARIAnT) 2 campaign. Measurements were made on the 25-meter sample line portion of the system using multiple, well characterized particle sizing instruments to obtain the penetration efficiencies. An agreement of ± 15% was obtained between the measured and the ARP6481 method penetrations for the 25-meter sample line portion of the system. Measurements of VPR penetration efficiency were also made to verify its performance for aviation nvPM number. The research also demonstrated the difficulty of making system loss measurements and substantiates the E-31 decision to predict rather than measure system losses.

Regional nerve blockade for early analgesic management of elderly patients with hip fracture - a narrative review.

Elderly patients with hip fracture experience high morbidity and mortality, and are often undertreated for pain. Acute pain management in the elderly is challenging, with physiological frailty, medical comorbidities and cognitive impairment commonly compounding pain assessment and treatment. Guidelines outlining current best practice for acute pain management in the elderly now exist, but evidence suggests that practice remains variable and there continues to be scope for improvement. We conducted a narrative review of the literature to examine the challenges of acute pain management in the elderly, and to evaluate evidence for the role of regional nerve blocks for acute pain associated with hip fracture in the elderly. There is consistent evidence that regional nerve blocks can effectively reduce pain associated with hip fracture, providing rapid-onset, site-specific analgesia that is more effective than standard systemic analgesia alone. There is also moderate evidence that nerve blocks may contribute to reduced rates of delirium, and some suggestion of reduced length of inpatient stay, morbidity and mortality, although limited evidence is available. Fascia iliaca blocks are emerging as a block of choice, with evidence they can be safely and rapidly administered under ultrasound guidance in the acute setting, by both trained medical and nursing staff, with good effect. Ideally, comprehensive pain protocols for elderly hip fracture patients are required, that integrate evidence-based fascia iliaca block use, timely and repeated pain assessment, and multidisciplinary orthogeriatric patient care.

Differential distribution of hypoxia-inducible factor 1-beta (ARNT or ARNT2) in mouse substantia nigra and ventral tegmental area.

Hypoxia has been proposed as a mechanism underlying gene-environment interactions in the neurodevelopmental model of schizophrenia, and hypoxia-inducible factor 1 (HIF-1) could mediate the interactions. In the current study, we analyzed the HIF-1 beta subunit, as formed by aryl hydrocarbon receptor nuclear translocator (ARNT) or ARNT2, in the mouse substantia nigra (SN) and the ventral tegmental area (VTA). We performed immunohistochemical studies of ARNT and ARNT2 in the adult mouse brain, and colocalization analyses, with specific emphasis on dopaminergic cells, i.e. tyrosine hydroxylase (TH) immunoreactive cells. Bioinformatic analyses identified shared protein partners for ARNT and ARNT2. ARNT immunoreactivity showed widespread neuronal labeling without overt regional specificity. We observed co-localization of ARNT and TH in the SN compacta and VTA. Nuclei strongly labeled for ARNT2 were observed in the SN reticulata, while only weak immunoreactivity for ARNT2 was found in TH-immunoreactive neurons in SN compacta and VTA. Stereological analysis showed that ARNT was preferentially expressed in dopaminergic neurons in SN compacta and VTA. Nuclei strongly labeled for ARNT2 were present in neocortex and CA1 of hippocampus. Differential expression of ARNT and ARNT2 in dopaminergic neurons may relate to the vulnerability of distinct dopaminergic projections to hypoxia and to functional vulnerability in schizophrenia and other neuropsychiatric disorders.

The impact of decreasing U.S. hip fracture rates on future hip fracture estimates.

SUMMARY: We examined age- and sex-specific hip fracture hospitalization rates among people aged 65 and older using 1990-2010 National Hospital Discharge Survey data. Trends calculated using Joinpoint regression analysis suggest that future increases in hip fractures due to the aging population will be largely offset by decreasing hip fracture rates among women. However, this trend will be counterbalanced by rising numbers of hip fractures among men. INTRODUCTION: From 1990 to 2006, age-adjusted U.S. hip fracture rates among people aged 65 years and older declined significantly. We wanted to determine whether decreasing age group-specific hip fracture rates might offset increases in hip fractures among the aging population over the next two decades. METHODS: This study used data from the National Hospital Discharge Survey, a national probability survey of inpatient discharges from nonfederal U.S. hospitals, to analyze hip fracture hospitalizations, defined as cases with first diagnosis coded ICD-9 CM 820. We analyzed trends in rates by sex and 10-year age groups using Joinpoint analysis software and used the results and projected population estimates to obtain the expected number of hip fractures in 2020 and 2050. RESULTS: Based on current age- and sex-specific trends in hip fracture hospitalization rates, the number of hip fractures is projected to rise 11.9 %-from 258,000 in 2010 to 289,000 (Projection Interval [PI] = 193,000-419,000) in 2030. The number of hip fractures among men is expected to increase 51.8 % (PI = 15.9-119.4 %) while the number among women is expected to decrease 3.5 % (PI = -44.3-37.3 %). These trends will affect the future distribution of hip fractures among the older population. CONCLUSIONS: Although the number of older people in the U.S.A. will increase appreciably over the next 20 years, the expected increase in the total number of hip fractures will be largely offset by decreasing hip fracture rates among women. However, this trend will be counterbalanced by rising numbers of hip fractures among men.

The impact of ingested potato type II inhibitors on the production of the major serine proteases in the gut of Helicoverpa armigera.

The flowers of the ornamental tobacco produce high levels of a series of 6 kDa serine protease inhibitors (NaPIs) that are effective inhibitors of trypsins and chymotrypsins from lepidopteran species. These inhibitors have a negative impact on the growth and development of lepidopteran larvae and have a potential role in plant protection. Here we investigate the effect of NaPIs on the activity and levels of serine proteases in the gut of Helicoverpa armigera larvae and explore the adaptive mechanisms larvae employ to overcome the negative effects of NaPIs in the diet. Polyclonal antibodies were raised against a Helicoverpa punctigera trypsin that is a target for NaPIs and two H. punctigera chymotrypsins; one that is resistant and one that is susceptible to inhibition by NaPIs. The antibodies were used to optimize procedures for extraction of proteases for immunoblot analysis and to assess the effect of NaPIs on the relative levels of the proteases in the gut and frass. We discovered that consumption of NaPIs did not lead to over-production of trypsins or chymotrypsins but did result in excessive loss of proteases to the frass.

Coexpression of potato type I and II proteinase inhibitors gives cotton plants protection against insect damage in the field.

Potato type I and II serine protease inhibitors are produced by solanaceous plants as a defense mechanism against insects and microbes. Nicotiana alata proteinase inhibitor (NaPI) is a multidomain potato type II inhibitor (pin II) that is produced at high levels in the female reproductive tissues of the ornamental tobacco, Nicotiana alata. The individual inhibitory domains of NaPI target the major classes of digestive enzymes, trypsin and chymotrypsin, in the gut of lepidopteran larval pests. Although consumption of NaPI dramatically reduced the growth and development of a major insect pest, Helicoverpa punctigera, we discovered that surviving larvae had high levels of chymotrypsin activity resistant to inhibition by NaPI. We found a potato type I inhibitor, Solanum tuberosum potato type I inhibitor (StPin1A), was a strong inhibitor of the NaPI-resistant chymotrypsin activity. The combined inhibitory effect of NaPI and StPin1A on H. armigera larval growth in the laboratory was reflected in the increased yield of cotton bolls in field trials of transgenic plants expressing both inhibitors. Better crop protection thus is achieved using combinations of inhibitors in which one class of proteinase inhibitor is used to match the genetic capacity of an insect to adapt to a second class of proteinase inhibitor.

Fall-related traumatic brain injury deaths and hospitalizations among older adults--United States, 2005.

PROBLEM: Among older adults, both unintentional falls and traumatic brain injuries (TBI) result in significant morbidity and mortality; however, only limited national data on fall-related TBI are available. METHOD: To examine the relationship between older adult falls and TBI deaths and hospitalizations, CDC analyzed 2005 data from the National Center for Health Statistics' National Vital Statistics System and the Agency for Healthcare Research and Quality's Nationwide Inpatient Sample. RESULTS: In 2005, among adults>or=65 years, there were 7946 fall-related TBI deaths and an estimated 56,423 hospitalizations for nonfatal fall-related TBI in the United States. Fall-related TBI accounted for 50.3% of unintentional fall deaths and 8.0% of nonfatal fall-related hospitalizations. SUMMARY: These findings underscore the need for greater dissemination and implementation of evidence-based fall prevention interventions.

Self-reported falls and fall-related injuries among persons aged>or=65 years--United States, 2006.

PROBLEM: In 2005, 15,802 persons aged>or=65 years died from fall injuries. How many older adults seek outpatient treatment for minor or moderate fall injuries is unknown. METHOD: To estimate the percentage of older adults who fell during the preceding three months, the Centers for Disease Control and Prevention (CDC) analyzed data from two questions about falls included in the 2006 Behavioral Risk Factor Surveillance System (BRFSS) survey. RESULTS: Approximately 5.8 million (15.9%) persons aged>or=65 years reported falling at least once during the preceding three months, and 1.8 million (31.3%) of those who fell sustained an injury that resulted in a doctor visit or restricted activity for at least one day. DISCUSSION: This report presents the first national estimates of the number and proportion of persons reporting fall-related injuries associated with either doctor visits or restricted activity. SUMMARY: The prevalence of falls reinforces the need for broader use of scientifically proven fall-prevention interventions. IMPACT ON INDUSTRY: Falls and fall-related injuries represent an enormous burden to individuals, society, and to our health care system. Because the U.S. population is aging, this problem will increase unless we take preventive action by broadly implementing evidence-based fall prevention programs. Such programs could appreciably decrease the incidence and health care costs of fall injuries, as well as greatly improve the quality of life for older adults.

Motor imagery of gait: a quantitative approach.

Motor imagery (MI) is widely used to study cognitive aspects of the neural control of action. Prior studies were mostly centred on hand and arm movements. Recently a few studies have used imagery tasks to explore the neurophysiology of human gait, but it remains unclear how to ascertain whether subjects actually perform imagery of gait as requested. Here we describe a new experimental protocol to quantify imagery of gait, by behaviourally distinguishing it from visual imagery (VI) processes and by showing its temporal correspondence with actual gait. Fourteen young healthy subjects performed two imagery tasks and an actual walking (AW) task. During both imagery tasks subjects were sitting on a chair and faced a computer screen that presented photographs of walking trajectories. During one task (MI), subjects had to imagine walking along the walking trajectory. During the other task (VI), subjects had to imagine seeing a disc moving along the walking trajectory. During the AW task, subjects had to physically walk along the same walking trajectory as presented on the photographs during the imagery tasks. We manipulated movement distance by changing the length of the walking trajectory, and movement difficulty by changing the width of the walking trajectory. Subjects reported onset and offset of both actual and imagined movements with a button press. The time between the two button presses was taken as the imagined or actual movement time (MT). MT increased with increasing path length and decreasing path width in all three tasks. Crucially, the effect of path width on MT was significantly stronger during MI and AW than during VI. The results demonstrate a high temporal correspondence between imagined and AW, suggesting that MI taps into similar cerebral resources as those used during actual gait. These results open the possibility of using this protocol for exploring neurophysiological correlates of gait control in humans.

The costs of fatal and non-fatal falls among older adults.

OBJECTIVE: To estimate the incidence and direct medical costs for fatal and non-fatal fall injuries among US adults aged >or=65 years in 2000, for three treatment settings stratified by age, sex, body region, and type of injury. METHODS: Incidence data came from the 2000 National Vital Statistics System, 2001 National Electronic Injury Surveillance System-All Injury Program, 2000 Health Care Utilization Program National Inpatient Sample, and 1999 Medical Expenditure Panel Survey. Costs for fatal falls came from Incidence and economic burden of injuries in the United States; costs for non-fatal falls were based on claims from the 1998 and 1999 Medicare fee-for-service 5% Standard Analytical Files. A case crossover approach was used to compare the monthly costs before and after the fall. RESULTS: In 2000, there were almost 10 300 fatal and 2.6 million medically treated non-fatal fall related injuries. Direct medical costs totaled 0.2 billion dollars for fatal and 19 billion dollars for non-fatal injuries. Of the non-fatal injury costs, 63% (12 billion dollars ) were for hospitalizations, 21% (4 billion dollars) were for emergency department visits, and 16% (3 billion dollars) were for treatment in outpatient settings. Medical expenditures for women, who comprised 58% of the older adult population, were 2-3 times higher than for men for all medical treatment settings. Fractures accounted for just 35% of non-fatal injuries but 61% of costs. CONCLUSIONS: Fall related injuries among older adults, especially among older women, are associated with substantial economic costs. Implementing effective intervention strategies could appreciably decrease the incidence and healthcare costs of these injuries.

Gender differences for non-fatal unintentional fall related injuries among older adults.

OBJECTIVES: To quantify gender differences for non-fatal unintentional fall related injuries among US adults age 65 years and older treated in hospital emergency departments (EDs). METHODS: The authors analyzed data from a nationally representative sample of ED visits for January 2001 through December 2001, available through the National Electronic Injury Surveillance System All Injury Program (NEISS-AIP). For each initial ED visit, coders record one principal diagnosis (usually the most severe) and one primary part of the body affected. RESULTS: Based on 22,560 cases, an estimated 1.64 million older adults were treated in EDs for unintentional fall injuries. Of these, approximately 1.16 million, or 70.5%, were women. Fractures, contusions/abrasions, and lacerations accounted for more than three quarters of all injuries. Rates for injury diagnoses were generally higher among women, most notably for fractures which were 2.2 times higher than for men. For all parts of the body, women's injury rates exceeded those of men. Rate ratios were greatest for injuries of the leg/foot (2.3), arm/hand (2.0), and lower trunk (2.0). The hospitalization rate for women was 1.8 times that for men. CONCLUSIONS: Among older adults, non-fatal fall related injuries disproportionately affected women. Much is known about effective fall prevention strategies. We need to refine, promote, and implement these interventions. Additional research is needed to tailor interventions for different populations and to determine gender differences in the underlying causes and/or circumstances of falls. This information is vital for developing and implementing targeted fall prevention strategies.

Interference effects demonstrate distinct roles for visual and motor imagery during the mental representation of human action.

Four experiments were completed to characterize the utilization of visual imagery and motor imagery during the mental representation of human action. In Experiment 1, movement time functions for a motor imagery human locomotion task conformed to a speed-accuracy trade-off similar to Fitts' Law, whereas those for a visual imagery object motion task did not. However, modality-specific interference effects in Experiment 2 demonstrate visual and motor imagery as cooperative processes when the action represented is tied to visual coordinates in space. Biomechanic-specific motor interference effects found in Experiment 3 suggest one basis for separation of processing channels within motor imagery. Finally, in Experiment 4 representations of motor actions were found to be generated using only visual imagery under certain circumstances: namely, when the imaginer represented the motor action of another individual while placed at an opposing viewpoint. These results suggest that the modality of representation recruited to generate images of human action is dependent on the dynamic relationship between the individual, movement, and environment.

Recreational injuries among older Americans, 2001.

OBJECTIVE: To describe the epidemiology of non-fatal recreational injuries among older adults treated in United States emergency departments including national estimates of the number of injuries, types of recreational activities, and diagnoses. METHODS: Injury data were provided by the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP), a nationally representative subsample of 66 out of 100 NEISS hospitals. Potential cases were identified using the NEISS-AIP definition of a sport and recreation injury. The authors then reviewed the two line narrative to identify injuries related to participation in a sport or recreational activity among men and women more than 64 years old. RESULTS: In 2001, an estimated 62 164 (95% confidence interval 35 570 to 88 758) persons >/=65 years old were treated in emergency departments for injuries sustained while participating in sport or recreational activities. The overall injury rate was 177.3/100 000 population with higher rates for men (242.5/100 000) than for women (151.3/100 000). Exercising caused 30% of injuries among women and bicycling caused 17% of injuries among men. Twenty seven percent of all treated injuries were fractures and women (34%) were more likely than men (21%) to suffer fractures. CONCLUSIONS: Recreational activities were a frequent cause of injuries among older adults. Fractures were common. Many of these injuries are potentially preventable. As more persons engage in recreational activities, applying known injury prevention strategies will help to reduce the incidence of these injuries.

The formation of cluster elliptical galaxies as revealed by extensive star formation.

The most massive galaxies in the present-day Universe are found to lie in the centres of rich clusters. They have old, coeval stellar populations suggesting that the bulk of their stars must have formed at early epochs in spectacular starbursts, which should be luminous phenomena when observed at submillimetre wavelengths. The most popular model of galaxy formation predicts that these galaxies form in proto-clusters at high-density peaks in the early Universe. Such peaks are indicated by massive high-redshift radio galaxies. Here we report deep submillimetre mapping of seven high-redshift radio galaxies and their environments. These data confirm not only the presence of spatially extended regions of massive star-formation activity in the radio galaxies themselves, but also in companion objects previously undetected at any wavelength. The prevalence, orientation, and inferred masses of these submillimetre companion galaxies suggest that we are witnessing the synchronous formation of the most luminous elliptical galaxies found today at the centres of rich clusters of galaxies.

Motor vehicle and fall related deaths among older Americans 1990-98: sex, race, and ethnic disparities.

OBJECTIVES: To examine differences in motor vehicle and fall related death rates among older adults by sex, race, and ethnicity. METHODS: Annual mortality tapes for 1990-98 provided demographic data including race and ethnicity, date, and cause of death. Trend analyses were conducted using Poisson regression. RESULTS: From 1990-98, overall motor vehicle related death rates remained stable while death rates from unintentional falls increased. Motor vehicle and fall related death rates were higher among men. Motor vehicle related death rates were higher among people of color while fall related death rates were higher among whites. Among whites, fall death rates increased significantly during the study period, with an annual relative increase of 3.6% for men and 3.2% for women. CONCLUSIONS: The risk of death from motor vehicle and fall related injuries among older adults differed by sex, race and ethnicity, results obscured by simple age and sex specific death rates. This study found important patterns and disparities in these death rates by race and ethnicity useful for identifying high risk groups and guiding prevention strategies.