Factors associated with persistent opioid use 6-12 months after primary total knee arthroplasty.

Persistent pain following knee arthroplasty occurs in up to 20% of patients and may require ongoing analgesia, including extended opioid administration. A comprehensive secondary analysis was performed from results of a study that considered persistent postoperative pain in 242 patients who underwent unilateral knee arthroplasty using a standardised enhanced recovery programme. Opioid prescribing for 12 months before and 12 months after surgery was evaluated and converted to oral morphine equivalents. Demographic, functional, psychological and pain questionnaires were completed along with quantitative sensory testing and genetic analysis. Forty-nine percent of patients had at least one opioid prescription in the 12 months before surgery. Opioid prescriptions were filled in 93% of patients from discharge to 3 months and in 27% of patients ≥6 months after surgery. Persistent opioid use ≥6 months after surgery was strongly associated with pre-operative opioid use (RR 3.2, p < 0.001 (95%CI 1.9-5.4)). The median (IQR [range]) oral morphine equivalent daily dose was 3.6 (0.9-10.5 [0-100.0]) mg pre-operatively, 35.0 (22.5-52.5 [4.6-180.0]) mg in hospital, 12.8 (5.1-24.8 [0-57.9]) mg from discharge to 3 months and 5.9 (4.5-12.0 [0-44.5]) mg at ≥6 months following surgery. Predictors of increased daily oral morphine equivalent ≥6 months after surgery included increased average daily oral morphine equivalent dose compared with previous values (lag), increased body mass index and three or more comorbid pain sites. Persistent opioid use was not associated with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (RR 1.003, p = 0.655, 95%CI 0.65-1.002) or WOMAC function (RR 1.001, p = 0.99, 95%CI 0.99-1.03) outcomes 6 months after surgery. There was no association between persistent opioid use and pre-operative quantitative sensory testing results or psychological distress. Pre-operatively, patients with a higher body mass index, more comorbid pain sites and those who had filled an opioid prescription in the last 12 months, were at increased risk of persistent opioid use and a higher oral morphine equivalent daily dose ≥ 6 months after surgery. Strategies need to be developed to limit dose and duration of persistent opioid use in patients following knee arthroplasty surgery.

The effect of intra-operative hypotension on acute kidney injury, postoperative mortality and length of stay following emergency hip fracture surgery.

The association between intra-operative hypotension and postoperative acute kidney injury, mortality and length of stay has not been comprehensively evaluated in a large single-centre hip fracture population. We analysed electronic anaesthesia records of 1063 patients undergoing unilateral hip fracture surgery, collected from 2015 to 2018. Acute kidney injury, 3-, 30- and 365-day mortality and length of stay were evaluated to assess the relationship between intra-operative hypotension absolute values (≤ 55, 60, 65, 70 and 75 mmHg) and duration of hypotension. The rate of acute kidney injury was 23.7%, mortality at 3-, 30- and 365 days was 3.7%, 8.0% and 25.3%, respectively, and median (IQR [range]) length of stay 8 (6-12 [0-99]) days. Median (IQR [range]) time ≤ MAP 55, 60, 65, 70 and 75 mmHg was 0 (0-0.5[0-72.1]); 0 (0-4.4 [0-104.9]); 2.2 (0-8.7 [0-144.2]); 6.6 (2.2-19.7 [0-198.8]); 17.5 (6.6-37.1 [0-216.3]) minutes, and percentage of surgery time below these thresholds was 1%, 2.5%, 7.9%, 12% and 21% respectively. There were some univariate associations between hypotension and mortality; however, these were no longer evident in multivariable analysis. Multivariable analysis found no association between hypotension and acute kidney injury. Acute kidney injury was associated with male sex, antihypertensive medications and cardiac/renal comorbidities. Three-day mortality was associated with delay to surgery ? 48 hours, whilst 30-day and 365-day mortality was associated with delay to surgery ≥ 48 hours, impaired cognition and cardiac/renal comorbidities. While the rate of acute kidney injury was similar to other studies, use of vasopressors and fluids to reduce the time spent at hypotensive levels failed to reduce this complication. Intra-operative hypotension at the levels observed in this cohort may not be an important determinant of acute kidney injury, postoperative mortality and length of stay.

Steroids to reduce the impact on delirium (STRIDE): a double-blind, randomised, placebo-controlled feasibility trial of pre-operative dexamethasone in people with hip fracture.

Neuro-inflammation may be important in the pathogenesis of postoperative delirium following hip fracture surgery. Studies have suggested a potential role for steroids in reducing postoperative delirium; however, the potential efficacy and safety of pre-operative high-dose dexamethasone in this specific population is largely unknown. Conducting such a study could be challenging, considering the multidisciplinary team involvement and the emergency nature of the surgery. The aim of this study was to assess feasibility and effectiveness of dexamethasone given as early as possible following hospital admission for hip fracture, to inform whether a full-scale trial is warranted. This single-centre, randomised, double-blind, placebo-controlled study randomly allocated 79 participants undergoing hip fracture surgery to dexamethasone 20 mg or placebo pre-operatively. Eligibility and recruitment rates, timing of the intervention and adverse events were recorded. Incidence and severity of postoperative delirium were assessed using the 4AT delirium screening tool and the Memorial Delirium Assessment Scale. Postoperative pain, length of stay and mortality were also assessed. The eligibility rate for inclusion was 178/527 (34%), and 57/178 (32%) of eligible patients presented to hospital when no researcher was available (e.g. after-hours, weekends, public holidays). Recruitment was limited mainly by ethical limitations (not including patients with impaired cognition) and lack of weekend staffing. Median (IQR [range]) time from emergency department admission to drug administration was 13.3 (5.9-17.6 [1.8-139.6]) hours. There was a significant difference in delirium severity scores, favouring the dexamethasone group: median (IQR [range]) 5 (3-6 [3-7]) vs. 9 (6-13 [5-14]) in the placebo group, with the probability of superiority effect size being 0.89, p = 0.010. Delirium incidence did not differ between groups: 6/40 (15%) in the dexamethasone group vs. 9/39 (23%) in the placebo group, relative risk (95%CI) 0.65 (0.22-1.65), p = 0.360). A larger randomised controlled trial is feasible and ideally this should include people with existing cognitive impairment, seven days-a-week cover and a multicentre design.

Persistent postoperative pain after total knee arthroplasty: a prospective cohort study of potential risk factors.

BACKGROUND: Persistent postoperative pain (PPP) is common after total knee arthroplasty (TKA). The primary aim of this prospective cohort study was to identify important predictors of moderate to severe PPP 6 and 12 months after TKA. METHODS: Consenting patients (n=300) undergoing primary unilateral TKA attended a preoperative session to collect clinical information (age, gender, BMI, preoperative knee pain, comorbid pain, likely neuropathic pain) and psychological variables (depression, anxiety, catastrophising, expected pain). Quantitative sensory testing (pressure pain thresholds, temporal summation, conditioned pain modulation) was performed, and blood samples were obtained for subsequent genotyping of OPRM1 and COMT. Acute postoperative pain was measured at rest and during movement. Surgical factors (surgery time, patella resurfacing, anaesthetic type) were collected after operation. Follow-up questionnaires were sent 6 and 12 months after surgery. Multivariate logistic regression was used to identify predictors of PPP. RESULTS: The prevalence of moderate to severe PPP was 21% (n=60) and 16% (n=45) 6 and 12 months after surgery, with 55% (n=33) and 60% (n=31) of PPP likely neuropathic in nature. At 6 months, a combination of preoperative pain intensity, expected pain, trait anxiety, and temporal summation (Akaike information criterion, 309.9; area under receiver operating characteristic (ROC) curve, 0.70) was able to correctly classify 66% of patients into moderate to severe PPP and no to mild PPP groups. At 12 months, preoperative pain intensity, expected pain, and trait anxiety (Akaike information criterion, 286.8; area under ROC curve, 0.66) correctly classified 66% of patients. CONCLUSIONS: Findings from this study highlight several factors that may be targeted in future intervention studies to reduce the development of PPP. TRIAL REGISTRY NUMBER: ACTRN12612001089820.

Transcranial direct current stimulation for upper limb neuropathic pain: A double-blind randomized controlled trial.

BACKGROUND: While promising, there are mixed findings for the efficacy of transcranial direct current stimulation (tDCS) for the management of chronic pain. The goal of this study was to evaluate the effect of anodal tDCS on pain and function in people with upper limb neuropathic pain. METHODS: The study was a double-blinded, randomized controlled trial. Thirty participants were randomly allocated into active and sham tDCS groups. Baseline assessments of pain and function, as well as quantitative sensory testing (QST) to probe the function of the nociceptive system, were undertaken prior to participants receiving 5 days of active or sham anodal tDCS (1 mA) over the primary motor cortex. The outcome measures were re-assessed 1, 3 and 8 weeks following the intervention. RESULTS: Group analyses revealed no significant improvement in pain, function, or QST measures over time in either group. However, there were significantly more individual responders (≥30% change in pain) in the active compared to the sham tDCS group at the final follow-up. In the active group, there was a significant correlation indicating those with higher baseline pain had greater pain relief. CONCLUSIONS: On group analyses, no evidence was provided that 1 mA tDCS is beneficial for people with upper limb neuropathic pain, although it may provide lasting pain relief for some individuals. SIGNIFICANCE: At the group level, we found no evidence that 5 days of active 1 mA tDCS is effective for people with upper limb neuropathic pain. However, there were more individual responders in the active tDCS group compared to sham, and those who responded early after treatment experienced sustained pain relief.

TENS Alleviates Muscle Weakness Attributable to Attenuation of Ia Afferents.

Quadriceps weakness is a notable problem following knee damage. Research has shown effectiveness of TENS in improving Quadriceps weakness associated with arthrogenic muscle inhibition. However, these studies were not focused upon short term delivery of TENS, nor did they examine the potential mechanism(s). The present study examined the effect of 25-30 s of TENS upon weakness induced temporarily by a prolonged vibration. Subjects performed eccentric MVCs under 2 conditions (TENS and no-TENS). First, MVC was measured at baseline. For the TENS condition, TENS was applied to each subject's knee joint during a second MVC measurement after vibration. For no-TENS condition, TENS was not applied during the 2nd MVC measurement. MVC between pre-and post-vibration stimulation were compared across the 2 conditions. The results showed that MVC and EMG of TENS-condition was larger than that of no-TENS condition. Our results suggest that TENS could partially restore α-motoneuron activation, despite the induced dysfunctional γ-loop. These results suggest that mechanisms independent of the γ-loop such as a direct facilitation of the QF α-motoneuron pool by a long latency spinal-reflex and/or supraspinal mechanisms appear more likely to be responsible. The findings provide further support for utilizing TENS, even when γ-loop dysfunction is present following joint damage.

Predictors of persistent pain after total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Several studies have identified clinical, psychosocial, patient characteristic, and perioperative variables that are associated with persistent postsurgical pain; however, the relative effect of these variables has yet to be quantified. The aim of the study was to provide a systematic review and meta-analysis of predictor variables associated with persistent pain after total knee arthroplasty (TKA). METHODS: Included studies were required to measure predictor variables prior to or at the time of surgery, include a pain outcome measure at least 3 months post-TKA, and include a statistical analysis of the effect of the predictor variable(s) on the outcome measure. Counts were undertaken of the number of times each predictor was analysed and the number of times it was found to have a significant relationship with persistent pain. Separate meta-analyses were performed to determine the effect size of each predictor on persistent pain. Outcomes from studies implementing uni- and multivariable statistical models were analysed separately. RESULTS: Thirty-two studies involving almost 30 000 patients were included in the review. Preoperative pain was the predictor that most commonly demonstrated a significant relationship with persistent pain across uni- and multivariable analyses. In the meta-analyses of data from univariate models, the largest effect sizes were found for: other pain sites, catastrophizing, and depression. For data from multivariate models, significant effects were evident for: catastrophizing, preoperative pain, mental health, and comorbidities. CONCLUSIONS: Catastrophizing, mental health, preoperative knee pain, and pain at other sites are the strongest independent predictors of persistent pain after TKA.

A herd health approach to dairy cow nutrition and production diseases of the transition cow.

This paper presents a practical, on-farm approach for the monitoring and prevention of production disease in dairy cattle. This integrated approach, should be used in an interdisciplinary way by farmers, veterinarians, nutrition advisors and other relevant professionals for the improvement of animal health and welfare and producer profitability. The key areas that form the basis for this approach are body condition score management, negative energy balance, hypocalcaemia, rumen health and trace element status. Monitoring criteria are described for each of these key areas, which when considered collectively, will facilitate the assessment of dairy cow health with regard to clinical and subclinical disease. The criteria, which are informed by published scientific literature, are based on farm management and environmental factors, clinical data, milk production records, dietary analysis, and assessment of blood and liver concentrations of various metabolites or trace elements. The aim is to review the efficacy of production disease control measures currently in place, and if necessary to modify them or formulate new ones.

Preparation and properties of gallaborane, GaBH(6): structure of the gaseous molecule H(2)Ga(mu-H)(2)BH(2) as determined by vibrational, electron diffraction, and ab initio studies, and structure of the crystalline solid at 110 K as determined by X-ray diffraction.

Gallaborane (GaBH(6), 1), synthesized by the metathesis of LiBH(4) with [H(2)GaCl](n) at ca. 250 K, has been characterized by chemical analysis and by its IR and (1)H and (11)B NMR spectra. The IR spectrum of the vapor at low pressure implies the presence of only one species, viz. H(2)Ga(mu-H)(2)BH(2), with a diborane-like structure conforming to C(2v) symmetry. The structure of this molecule has been determined by gas-phase electron diffraction (GED) measurements afforced by the results of ab initio molecular orbital calculations. Hence the principal distances (r(alpha) in A) and angles ( angle(alpha) in deg) are as follows: r(Ga.B), 2.197(3); r(Ga-H(t)), 1.555(6); r(Ga-H(b)), 1.800(6); r(B-H(t)), 1.189(7); r(B-H(b)), 1.286(7); angleH(b)-Ga-H(b), 71.6(4); and angleH(b)-B-H(b), 110.0(5) (t = terminal, b = bridging). Aggregation of the molecules occurs in the condensed phases. X-ray crystallographic studies of a single crystal at 110 K reveal a polymeric network with helical chains made up of alternating pseudotetrahedral GaH(4) and BH(4) units linked through single hydrogen bridges; the average Ga.B distance is now 2.473(7) A. The compound decomposes in the condensed phases at temperatures exceeding ca. 240 K with the formation of elemental Ga and H(2) and B(2)H(6). The reactions with NH(3), Me(3)N, and Me(3)P are also described.

Postmortem biochemical markers of experimentally induced hypomagnesaemic tetany in cattle.

Severe hypomagnesaemia and tetany were induced in 10 lactating cows by feeding them semi-synthetic low magnesium diets and the animals were used to study the stability of postmortem markers of hypomagnesaemic tetany. There were significant relationships between the concentrations of magnesium in either cerebrospinal fluid (CSF) or plasma and either aqueous or vitreous humour. The onset of hypomagnesamic tetany was also associated with low magnesium concentrations in plasma, CSF and aqueous and vitreous humour. Magnesium concentrations less than 0.25 mmol/litre in fresh aqueous humour may be indicative of severe hypomagnesaemia and possible tetany in lactating cows, but the concentration of magnesium in aqueous humour was unstable postmortem. The concentration of magnesium in vitreous humour was relatively stable and a concentration of less than 0.55 mmol/litre could be used as a diagnostic marker of tetany in cattle for up to at least 48 hours postmortem, at ambient temperatures typical of Northern Ireland.

Expression of steroidogenic factor 1 in the testis requires an E box and CCAAT box in its promoter proximal region.

Steroidogenic factor 1 (SF-1), also known as adrenal 4-binding protein, is a member of the nuclear hormone receptor family that regulates transcription of genes encoding hormones and steroidogenic enzymes important to the function of the hypothalamic-pituitary-gonadal axis. The mammalian Ftz-F1 gene encodes SF-1 and is required for development of adrenal glands and gonads. To better understand the mechanisms regulating this gene in the gonads, we have examined its expression in the testis and characterized the promoter region for SF-1 in two testicular cell types. SF-1 promoter activity was examined in primary cultures of Sertoli cells and cell lines representative of Sertoli and Leydig cells. Deletion mutagenesis of the promoter identified several regions: both 5' and 3' to the transcriptional start sites that are important for transcriptional activity. Two elements, an E box and a CCAAT box, were found to be important for SF-1 transcription in the testis. An oligodeoxynucleotide containing both of these elements bound three specific protein complexes. The binding of one complex required only sequences within the E box and cross-reacted with antibodies against the basic helix-loop-helix ZIP proteins USF1 and USF2. A second specific complex required sequences within both the E box and CCAAT box for efficient binding, while a third complex predominantly interacted with sequences within the CCAAT motif. The presence of multiple protein complexes binding these sites suggests that regulation through these elements may involve interactions with different factors that depend on the state of the cell and its environment.

Monochlorogallane: physical properties and structure of the gaseous molecule H2Ga(mu-Cl)2GaH2 as determined by vibrational, electron diffraction, and ab initio studies.

Monochlorogallane, synthesized by the metathesis of gallium(III) chloride with an excess of trimethylsilane at ca. 250 K, has been characterized by chemical analysis, by its IR, Raman, and 1H NMR spectra, and by the products of its reaction with trimethylamine. The vibrational spectra of the vapor species isolated in solid Ar, N2, or CH4 matrixes at ca. 12 K imply the presence of only one species, viz. the dimer with an equilibrium structure conforming to D2h symmetry. The structure of this molecule has been determined by gas-phase electron diffraction (GED) measurements augmented by the results of ab initio molecular orbital calculations. An equilibrium structure with D2h symmetry has been assumed in the analysis of the electron diffraction pattern. However, as the molecule has a very low frequency Ga(mu-Cl)2Ga ring-puckering mode, a dynamic model was used to describe it with the aid of a set of pseudoconformers spaced at even intervals (deltadelta = 5 degrees, deltamax, = 20 delta) around the ring-puckering angle delta and Boltzmann-weighted according to a quartic potential V(delta) = V4delta4 + V2delta2. The differences in bond distances and angles between the different pseudoconformers were constrained to the values derived from the ab initio calculations employing second-order Moller-Plesset (MP2) methods (with all the electrons included in the correlation calculations) and a 6-311G(d) basis set. The results for the weighted average of the principal distances (ralpha) and angles (

Reminding technology for prospective memory disability: a case study.

Congenital or acquired brain damage resulting in prospective memory loss can make a child unable to become independent of care givers. This note describes a memory aid developed for a 17 year old with spina bifida and hydrocephalus who requires continual reminding to perform health maintenance tasks such as medication and feeding. Off-the-shelf computer hardware and software were used to make a reminding system that logged task completion information. Logging is a unique feature of this system, permitting review of the user's response to reminders for health or rehabilitative purposes. The system reduced the need to remind rate from > 75% to less than 10% of the time. Reminding rates returned to > 75% upon removal of the system. With the system this adolescent achieved more independent health maintenance. Weight and power requirements make this system embodiment impractical for general wheelchair use, but the technology in currently available pocket units may support the necessary functions.

Root surface removal with diamond-coated ultrasonic instruments: an in vitro and SEM study.

Adequate root preparation in periodontal procedures includes the removal of plaque, calculus, and perhaps contaminated cementum and dentin. The purpose of this study was to evaluate and compare the amount of root surface removal and residual surface texture using similarly shaped regular (US) and both fine (FINDIAM) and medium (MEDDIAM) grit diamond-coated ultrasonic inserts. Forty-five (45) premolars extracted for orthodontic reasons were randomly divided into 3 groups of 15 teeth each. They were individually mounted in a jig and instrumented with a standardized 500 gram force while they were moved a precise horizontal distance of 12 mm over a 1.2 second period using specially designed and computer controlled instrumentation. Three measurements were made to the nearest 0.0005" at 3 points along the test area before instrumentation and after 10 and 20 strokes. The mean depth of root structure removed was US 5.8 +/- 6.6 microns, FINDIAM 50.1 +/- 14.2 microns, MEDDIAM 30.8 +/- 12.1 microns, after 10 strokes, and US 12.7 +/- 10.9 microns, FINDIAM 83.3 +/- 20.1 microns, MEDDIAM 58.7 +/- 17.9 microns after 20 strokes, respectively. All 3 instruments were different from each other (P < 0.001) in the 10 stroke group, while in the 20 stroke group FINDIAM and MEDDIAM were different from US (P < 0.001), but not from each other. Only FINDIAM showed a significant difference between 10 and 20 stroke values for depth of root removal. Modified loss of tooth substance index SEM scores indicated increasingly greater root surface roughness from US to FINDIAM to MEDDIAM. Substantially greater root surface removal and greater residual root surface roughness occurred with diamond-coated ultrasonic inserts under standardized in vitro conditions. These results suggest that caution should be used with diamond-coated ultrasonic instruments during periodontal root planing procedures.

Pancreas disease in Atlantic salmon (Salmo salar) and vitamin E supplementation.

A study was instigated to investigate the histopathological and clinical pathological lesions associated with a naturally occurring pancreas disease (PD) outbreak in farmed Atlantic salmon. An attempt was made to reduce the severity of PD and associated lesions by altering the antioxidative and peroxidative substrates in the diets. The results do not support the hypothesis that PD leads to a vitamin E deficiency which induces a myopathy. PD was not associated with a reduction in tissue vitamin E concentrations. Despite high tissue vitamin E concentrations, pancreatic lesions and cardiac and skeletal myopathy occurred almost simultaneously. Severe myopathy appeared to be associated with high mortality. Dietary vitamin E concentrations > 500 mg/kg did not increase plasma and muscle vitamin E concentrations, which appear to be saturated. Liver concentrations were also high. However, differing concentrations of dietary vitamin E and fat were associated with differing mortality rates.

Determination of ivermectin residues in the tissues of Atlantic salmon (Salmo salar) using HPLC with fluorescence detection.

A sensitive, accurate and reproducible assay for the determination of residual concentrations of ivermectin in the tissues of farmed Atlantic salmon is described. The assay employs the clean-up of an acetonitrile extract of salmon tissue on a Bond-Elut C8 column, followed by derivatization with trifluoroacetic acid anhydride. Following separation using HPLC, 22,23-dihydroavermectin B1a is determined using fluorescence detection. The limit of detection of the assay is 1 ng per g tissue. Liver, taken from fish treated experimentally with ivermectin, was found to contain higher concentrations of 22,23-dihydroavermectin B1a than any other tissue examined. The half-life of 22,23-dihydroavermectin B1a was similar in all tissues studied, ranging from 89 to 98 degree days.

Improved performance in commercial broiler flocks with subclinical infectious bursal disease when fed diets containing increased concentrations of vitamin E.

The economic effects of increased vitamin E supplementation in 79 commercial broiler flocks incorporating over 1.5 million birds was assessed. Approximately half of the flocks were fed on either a high (178 IU/kg) or normal (48 IU/kg) vitamin E-containing diet. In addition, in approximately half of the flocks subclinical infectious bursal disease (IBD) was present. Analysis of the performance data demonstrated that flocks with subclinical IBD were consistently worse (P< 0.001) for net income, feed conversion ratio and average weight per bird than flocks without the subclinical disease. The trial also indicated that the average net income of flocks with subclinical IBD and fed a high vitamin E-containing diet was 10% better (P < 0.05) than flocks with subclinical IBD and fed a normal vitamin E-containing diet. However, the trial also demonstrated that the difference between the average net income achieved by flocks without subclinical IBD and being fed on either a high or a normal vitamin E-containing diet was only 2% and not significantly different. It is suggested that the increased improved performance from high vitamin E-containing diets recorded in flocks with subclinical IBS is due to enhanced immunocompetence and increased resistance to disease. It is also suggested that under field conditions, high dietary inputs of vitamin E are most beneficial where there is a challenge to the host's defence system and significantly improved performance will occur more predictably under such conditions.