Biomechanical evaluation of three adjunctive methods of orthopedic tension band-wire fixation to augment simulated patella tendon repairs in dogs.

OBJECTIVE: To evaluate the effects of three adjunctive methods of tension band wire fixation (TBWF) on the biomechanical properties, gap formation, and failure mode in simulated canine patella tendon rupture (RPT). STUDY DESIGN: Randomized, ex vivo. SAMPLE POPULATION: Paired hindlimbs from 32 dog cadavers. METHODS: Patellar tendons (PTs) and associated bone-muscle-tendon units were harvested. Each PT was transected then sutured using a core locking loop and simple continuous epitendinous pattern. Each hindlimb was randomly assigned to one of three groups (n = 18 hindlimbs/group) using 18 gauge 316 L wire, anchored to the tibial crest distally, to perform transpatellar, suprapatellar, or combined tension band-wire (TBW) augmentation. Ten hindlimbs were utilized as control specimens. Yield, peak, and failure loads, stiffness, loads to 1 and 3 mm gap formation, and failure mode were evaluated. RESULTS: Combined transpatellar and suprapatellar TBW augmentation was superior to transpatellar or suprapatellar groups alone. Yield (p = .0008), peak (p = .004), and failure loads (p = .005) were greater for the combined group than for the transpatellar (p = .048) and suprapatellar groups (p = .01) respectively. There was no difference regarding the occurrence of 1 or 3 mm gap formation (1 mm, p = .05; 3 mm, p = .06); however, loads required to cause gap formation were greater in the combined group (p = .036). Mode of failure differed between techniques used for PT augmentation (p < .001). CONCLUSION: Combined transpatellar and suprapatellar adjunctive TBW augmentation for simulated PT repairs was biomechanically superior to either transpatellar or suprapatellar TBWF alone. CLINICAL SIGNIFICANCE: Combined suprapatellar and transpatellar TBWF may offer a viable surgical option for increased repair-site strength and greater loads to gap formation. Further studies investigating alternative techniques and materials for RPT repair augmentation are warranted.

Multiple MIS-C Readmissions and Giant Coronary Aneurysm After COVID-19 Illness and Vaccination: A Case Report.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) rarely involves delayed giant coronary aneurysms, multiple readmissions or occurrence after COVID-19 vaccination. METHODS: We describe a child with all 3 of these unusual features. We discuss his clinical presentation, medical management, review of the current literature and CDC guidance recommendations regarding further vaccinations. RESULTS: A 5-year-old boy had onset of MIS-C symptoms 55 days after COVID-19 illness and 15 days after receiving his first BNT162b2 COVID-19 vaccination. He was admitted 3 times for MIS-C, and twice after his steroid dose was tapered. On his initial admission, he was given intravenous immunoglobulin and steroids. During his second admission, new, moderate coronary dilation was noted, and he was treated with intravenous immunoglobulin and steroids. At his last admission, worsening coronary dilation was noted, and he was treated with infliximab and steroids. During follow-up, he had improvement in his coronary artery dilatation. However, his inflammatory markers increased after steroid wean, and his steroid taper was further extended, after which time his inflammatory markers improved. This is the only such reported case of a patient who was admitted 3 times for MIS-C complications after COVID-19 vaccination. CONCLUSION: MIS-C rarely involves delayed giant coronary aneurysms, multiple readmissions, or occurrence after COVID-19 vaccination. Whether our patient's COVID-19 vaccine 6 weeks after COVID-19 illness contributed to his MIS-C is unknown. After consultation with the CDC-funded Clinical Immunization Safety Assessment Project, the patient's care team decided against further COVID-19 vaccination until at least 3 months post normalization of inflammatory markers.

A draft Diabrotica virgifera virgifera genome: insights into control and host plant adaption by a major maize pest insect.

BACKGROUND: Adaptations by arthropod pests to host plant defenses of crops determine their impacts on agricultural production. The larval host range of western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), is restricted to maize and a few grasses. Resistance of D. v. virgifera to crop rotation practices and multiple insecticides contributes to its status as the most damaging pest of cultivated maize in North America and Europe. The extent to which adaptations by this pest contributes to host plant specialization remains unknown. RESULTS: A 2.42 Gb draft D. v. virgifera genome, Dvir_v2.0, was assembled from short shotgun reads and scaffolded using long-insert mate-pair, transcriptome and linked read data. K-mer analysis predicted a repeat content of ≥ 61.5%. Ortholog assignments for Dvir_2.0 RefSeq models predict a greater number of species-specific gene duplications, including expansions in ATP binding cassette transporter and chemosensory gene families, than in other Coleoptera. A majority of annotated D. v. virgifera cytochrome P450s belong to CYP4, 6, and 9 clades. A total of 5,404 transcripts were differentially-expressed between D. v. virgifera larvae fed maize roots compared to alternative host (Miscanthus), a marginal host (Panicum virgatum), a poor host (Sorghum bicolor) and starvation treatments; Among differentially-expressed transcripts, 1,908 were shared across treatments and the least number were between Miscanthus compared to maize. Differentially-expressed transcripts were enriched for putative spliceosome, proteosome, and intracellular transport functions. General stress pathway functions were unique and enriched among up-regulated transcripts in marginal host, poor host, and starvation responses compared to responses on primary (maize) and alternate hosts. CONCLUSIONS: Manual annotation of D. v. virgifera Dvir_2.0 RefSeq models predicted expansion of paralogs with gene families putatively involved in insecticide resistance and chemosensory perception. Our study also suggests that adaptations of D. v. virgifera larvae to feeding on an alternate host plant invoke fewer transcriptional changes compared to marginal or poor hosts. The shared up-regulation of stress response pathways between marginal host and poor host, and starvation treatments may reflect nutrient deprivation. This study provides insight into transcriptomic responses of larval feeding on different host plants and resources for genomic research on this economically significant pest of maize.

Metal reactivity is present in dogs with tibial plateau leveling osteotomy and total hip replacement implants.

OBJECTIVE: Determine whether dogs with well-functioning orthopedic metal implants can develop metal reactivity. SAMPLE: Client-owned dogs that had tibial plateau leveling osteotomy (TPLO) or total hip replacement (THR) implants for 12 months or more and control dogs with no implants. PROCEDURES: Lymphocyte transformation testing was performed by exposing peripheral blood lymphocytes to nickel (Ni), chromium (Cr), cobalt (Co), or a combination of these metals. Lymphocyte proliferation was assessed with flow cytometry. Lymphocyte stimulation indexes (SIs) were calculated. A SI > 2 was considered reactive. Median SIs of dogs in response to metal exposure were compared statistically. RESULTS: Samples from 10 dogs with TPLO, 12 dogs with THR, and 7 control dogs were analyzed. Six dogs out of 22 with metal implants had a reactive SI to 1 or more metals, while 2 of 7 control dogs had a SI > 2 when exposed to nickel only. When all metals were considered, no differences in metal reactivity were found between TPLO, THR, and control groups. CLINICAL RELEVANCE: Metal reactivity is present in dogs and can be identified using lymphocyte transformation testing. Reactivity to Ni is present in dogs with and without metal implants. Reactivity to Co and Cr occurs in some dogs with metal implants.

Neighborhood deprivation and obesity: Sex-specific effects of cross-sectional, cumulative and residential trajectory indicators.

Obesity is a long-term health issue that is becoming increasingly prevalent. Very few studies have considered the life course effects of neighborhood characteristics on obesity. In a sample of 35,856 adult participants (representative of the population of the Province of Quebec in Canada), we measured the association between neighborhood deprivation and obesity using logistic modelling on indicators of cross-sectional neighborhood deprivation, cumulative neighborhood deprivation and trajectories of neighborhood deprivation. For cross-sectional exposure, we found that females in our sample had higher odds of being affected by obesity when living in high-deprivation (OR 1.73, CI 1.41-2.13) or medium-deprivation neighborhoods (OR 1.27, CI 1.07-1.51) compared to females living in low-deprivation neighborhoods. Males also had higher odds of being affected by obesity when living in medium or high deprivation. For cumulative exposure to neighborhood deprivation, only females in the second highest category for longitudinal exposure to deprived neighborhoods had significantly higher odds of living with obesity (OR 1.89 CI 1.12-3.19) compared to females in the low cumulative exposure category. Using sequence analysis to determine neighborhood deprivation trajectories for up to 17 years, we found that females with a Deprived upward (OR 1.75 CI 1.10-2.78), an Average downward (OR 1.75 CI 1.08-2.84) or a Deprived trajectory (OR 1.81 CI 1.45-2.86) had higher odds of living with obesity compared to the Privileged trajectory. For males, there were no significant associations. Using trajectory indicators was beneficial to our analyses because this method shows that not only are individuals in low socioeconomic status neighborhoods at the end of their trajectory more susceptible to living with obesity, but so are those exposed to neighborhood deprivation at the beginning of their trajectory. These results could help to more precisely identify individuals at higher risk of developing obesity-related health issues.

The Genome of Rhyzopertha dominica (Fab.) (Coleoptera: Bostrichidae): Adaptation for Success.

The lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae), is a major global pest of cereal grains. Infestations are difficult to control as larvae feed inside grain kernels, and many populations are resistant to both contact insecticides and fumigants. We sequenced the genome of R. dominica to identify genes responsible for important biological functions and develop more targeted and efficacious management strategies. The genome was assembled from long read sequencing and long-range scaffolding technologies. The genome assembly is 479.1 Mb, close to the predicted genome size of 480.4 Mb by flow cytometry. This assembly is among the most contiguous beetle assemblies published to date, with 139 scaffolds, an N50 of 53.6 Mb, and L50 of 4, indicating chromosome-scale scaffolds. Predicted genes from biologically relevant groups were manually annotated using transcriptome data from adults and different larval tissues to guide annotation. The expansion of carbohydrase and serine peptidase genes suggest that they combine to enable efficient digestion of cereal proteins. A reduction in the copy number of several detoxification gene families relative to other coleopterans may reflect the low selective pressure on these genes in an insect that spends most of its life feeding internally. Chemoreceptor genes contain elevated numbers of pseudogenes for odorant receptors that also may be related to the recent ontogenetic shift of R. dominica to a diet consisting primarily of stored grains. Analysis of repetitive sequences will further define the evolution of bostrichid beetles compared to other species. The data overall contribute significantly to coleopteran genetic research.

Exploring social inequalities in healthcare trajectories following diagnosis of diabetes: a state sequence analysis of linked survey and administrative data.

BACKGROUND: Social inequalities in complications associated with diabetes mellitus persist. As a primary care sensitive condition (PCSC), this association could be related to differential access to primary care. Our objectives are to establish a typology of care trajectories following a new diagnosis, and to explore social determinants of trajectories. METHODS: We used the TorSaDe (The Care Trajectories-Enriched Data) cohort, which links Canadian Community Health Survey respondents to health administrative data. Care trajectories were mapped over a two-year period following a new diagnosis and analysed using state sequence and clustering methods. Associations between individual and geographic characteristics with trajectory types were assessed with multinomial logistic regression. RESULTS: Three trajectories were identified: Regular Family Physician (FP) Predominant, Specialist Physician Predominant, and Few Services. With Regular FP as the reference, males had higher odds of experiencing the Few Services trajectory, higher education was associated with higher odds of both the Few Services and the Specialist trajectories, and immigrants had higher odds of the Specialist trajectory. Diagnoses in a physician's office, as opposed to in hospital, were associated with higher odds of the Regular FP trajectory. CONCLUSIONS: The Regular FP trajectory most closely aligns with the management principles of the PCSC approach. We did not find strong evidence of social status privileging access to this trajectory. However, the association with location of diagnosis suggests that efforts to ensure patients diagnosed in hospital are well linked to a regular family physician for follow up may help to reduce unnecessary specialist use and meet PCSC goals.

Self-perceived health status among adults with obesity in Quebec: a cluster analysis.

PURPOSE: People with obesity are a highly heterogeneous group. Characterizing this heterogeneity may help to improve public health by offering adapted interventions and treatments to more homogeneous sub-groups among obese patients. This research aims to (1) identify distinct clusters of people with obesity based on demographic, behavioural, and clinical factors in the province of Quebec (Canada) and (2) assess the association of these clusters with selfperceived health. METHODS: We conducted a sex specific cluster analysis (multiple correspondence analysis and hierarchical clustering) of adults with body mass index (BMI) ≥ 30 kg/m2 from the 2015-2016 Canadian Community Health Survey in Quebec. Clusters were based on demographic, clinical, and behavioural characteristics. The clusters were tested for association with poor selfperceived health using logistic regression. RESULTS: Three clusters of individuals with obesity were identified. These were (1) young individuals, (2) people with higher levels of depression and anxiety, and (3) older adults with high comorbidity. Those with high levels of depression and anxiety (9% of men vs. 13% of women) were associated with the poorest selfperceived health. CONCLUSIONS: People with obesity in Quebec can be categorized into three clusters based on demographic, clinical, and behavioural characteristics. The findings of this study draw attention to the need to examine the coexistence of obesity with depression and anxiety, particularly as it relates to selfperceived health.

Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression.

Opioid-induced respiratory depression (OIRD) confers significant morbidity, but its onset can be challenging to recognize. Pain or stimulation effects of conversation may mask or attenuate common clinical manifestations of OIRD. We asked whether pupillary unrest could provide an objective signal of opioid exposure, and whether this signal would be independent from the confounding influence of extrinsic stimulation. We conducted a cross-over trial of healthy volunteers using identical remifentanil infusions separated by a washout period; in both, pupillary unrest in ambient light (PUAL) was measured at 2.5-min intervals. During one infusion, investigators continuously engaged the subject in conversation, while in the other, a quiet environment was maintained; measures of respiratory depression were compared under each condition. We tested PUAL's relationship to estimated opioid concentration under quiet conditions, measured PUAL's discrimination of lower versus higher opioid exposure using receiver operating characteristic (ROC) analysis, and assessed the effect of stimulation on PUAL versus opioid using mixed effects regression. Respiratory depression occurred more frequently under quiet conditions (p < 0.0001). Under both conditions, PUAL declined significantly over the course of the remifentanil infusion and rose during recovery (p < 0.0001). PUAL showed excellent discrimination in distinguishing higher versus absent-moderate opioid exposure (AUROC = 0.957 [0.929 to 0.985]), but was unaffected by interactive versus quiet conditions (mean difference, interactive - quiet = - 0.007, 95% CI - 0.016 to 0.002). PUAL is a consistent indicator of opioid effect, and distinguishes higher opioid concentrations independently of the stimulating effects of conversational interaction. Under equivalent opioid exposure, conversational interaction delayed the onset and minimized the severity of OIRD.Clinical trial registration: NCT04301895.

Risk factors and outcomes associated with postoperative ileus following ileostomy formation: a retrospective study.

BACKGROUND: Postoperative ileus (POI) is associated with increased patient discomfort, length of stay (LOS), and healthcare cost. There is a paucity of literature examining POI in patients who have an ileostomy formed at the time of surgery. We aimed to identify risk factors for and outcomes associated with POI following ileostomy formation. METHODS: We included 261 consecutive non-emergent cases that included formation of an ileostomy by a board-certified colorectal surgeon at our institution from July 1, 2015, to June 30, 2020. Demographic, clinical, and intraoperative factors associated with increased odds of POI were evaluated. Post-procedure LOS, hospitalization cost, and re-admissions between patients with and without POI were compared. RESULTS: Out of 261 cases, 85 (32.6%) were associated with POI. Patients with POI had significantly higher body mass index (BMI) than those without POI (26.6 kg/m2 vs. 24.8kg/m2; p = 0.01). Intraoperatively, patients with POI had significantly longer procedure duration than those without POI (313 min vs. 279 min; p = 0.02). Patients with POI had a significantly higher net fluid balance at postoperative day (POD) 2 than those without POI (+ 2.65 L vs. + 1.80 L; p = 0.004), with POD2 fluid balance greater than + 807 mL (determined as the maximum Youden index for sensitivity over 80%) associated with a higher rate of POI (p = 0.006). This difference remained significant when adjusted for age, gender, BMI, pre-operative opioid use, procedure duration, and operative approach (p = 0.01). Patients with POI had significantly longer LOS (11.40 days vs. 5.12 days; p < 0.001) and direct cost of hospitalization ($38K vs. $22K; p < 0.001). CONCLUSIONS: Minimizing fluid overload, particularly in the first 48 h after surgery, may be a strategy to reduce POI in patients undergoing ileostomy formation, and thus decrease postoperative LOS and hospitalization cost. Fluid restriction, diuresis, and changes in diet advancement or early stoma intubation should be considered measures that may improve outcomes and should be studied more intensively.

Detection of opioid effect with pupillometry.

BACKGROUND: Opioids produce pupillary constriction but their impact on pupillary unrest and the dynamic parameters of the pupillary light reflex have not been characterized. Given the increasing use of portable pupillometers for care of critically ill patients, it is important to distinguish between opioid effects on the pupil versus those that have been reported to arise from traumatic and ischemic brain insults. We undertook this study to determine which pupillary responses are most profoundly and consistently affected by a progressive infusion of remifentanil. METHODS: We studied the effect of remifentanil on the pupil using two portable infrared pupillometers in 18 volunteers. One pupillometer measured pupillary unrest in ambient light (PUAL) and the other pupillometer measured neurological pupillary index (NPi), constriction velocity (CV), pupil diameter (PD), latency, and % reflex (% reflex) following a transient light flash. Remifentanil was administered at predetermined weight-adjusted rates to raise opioid effect site concentration up to a range known to produce respiratory depression and oxyhemoglobin desaturation, based on a previously published pharmacokinetic model. RESULTS: PUAL was ablated by remifentanil, declining 94 ± 6% from baseline at the time of maximum drug effect. Other pupillary measurements decreased 50-65% from baseline. NPi was unchanged. At the time of oxyhemoglobin desaturation, deviations in PD, CV, and % reflex were widely scattered, whereas PUAL consistently approached zero. CONCLUSION: PUAL is a highly specific indicator of central opioid effect. As a non-invasive measure, it may provide useful data to clinicians who prescribe opioids.

The Diagnostic Yield of Cone-Beam Computed Tomography for Degenerative Changes of the Temporomandibular Joint in Dogs.

Degenerative changes of the temporomandibular joint (DTMJ) may be diagnosed via cone - beam computed tomography (CBCT). However, despite advancement in CBCT imaging, correlation of DTMJ features identified on CBCT with gross and histological findings is currently limited. This study aimed to correlate CBCT findings of DTMJ of dogs with gross and histopathologic changes. Temporomandibular joints (TMJ) (n = 38) from fresh cadaver heads of asymptomatic dogs (n = 19) were examined radiologically, macroscopically, and microscopically. Association of CBCT - detected DTMJ changes with gross and histological findings were statistically evaluated via kappa statistics and ordinal logistic mixed-effects models. The radiological changes observed on CBCT included joint space narrowing, subchondral/cortical bone changes (i.e., erosions or lysis), osteophytes, and subchondral bone sclerosis. Upon macroscopic evaluation, the majority of examined specimens had mild changes with cartilage defects and osteophytes affecting <10% of the total articular surface area. Histopathologic changes comprised splitting and degeneration of the fibrous cartilage layers, subchondral bone exposure, subchondral bone sclerosis, focal subchondral bone lysis, and occasional cell death. Subchondral sclerosis was the most prevalent finding radiologically and histologically with a fair to excellent agreement. Importantly, the more severe the TMJ degenerative changes, the higher the agreement between CBCT and histology. Based on the correlative results of statistical analysis, CBCT was found to be a suitable modality to evaluate DTMJ.

Examining longitudinal patterns of individual neighborhood deprivation trajectories in the province of Quebec: A sequence analysis application.

Exposure to neighborhood deprivation has been associated with a number of health, behavioral and sociological outcomes. However, many negative outcomes associated with deprivation have a long latency and may be influenced by varying exposure to neighborhoods throughout time. Capturing the longitudinal exposure to neighborhood deprivation is methodologically complex when one wishes to include life course notions of order, duration and timing. In a sample of 60,555 participants, aged 12 years and older (representative of the population of the Province of Quebec in Canada) our objectives were to: 1) Create an indicator for neighborhood deprivation trajectories; 2) compare trajectories with cross-sectional and cumulative neighborhood deprivation; 3) identify individual socioeconomic determinants of membership to a trajectory cluster. Using sequence analysis based on optimal matching and clustering around theoretical types, we grouped sequences in nine neighborhood deprivation trajectory clusters. We found that half (50%) of the participants were in a stable trajectory and did not transition significantly from one deprivation tertile to another during their sequence. A comparison between a cross-sectional indicator of neighborhood deprivation and the trajectories showed that only 42.2% of the participants had a cross-sectional deprivation at the index date representative of their whole trajectory. We also found, using logistic regression (adjusted for age, sex, number of residential moves) that having no high school diploma, living in a rural area and being an immigrant was strongly associated with a deprived stable trajectory. Sequence analysis is an effective tool to describe neighborhood deprivation trajectories in a sample representative of the Quebec population. Trajectories are a useful addition to a better understanding of the distribution of health outcomes because they provide information about the order and accumulation of longitudinal exposures to neighborhood and seem to be associated with specific individual socioeconomic characteristics such as education, urbanity, and immigration status.

Evaluation of two portable pupillometers to assess clinical utility.

BACKGROUND: Pupillometers have been proposed as clinical assessment tools. We compared two pupillometers to assess measurement agreement. MATERIALS & METHODS: We enrolled 30 subjects and simultaneously measured the pupil diameter and light reflex amplitude with an iPhone pupillometer and a portable infrared pupillometer. We then enrolled 40 additional subjects and made serial measurements with each device. RESULTS: Failure occurred in 30% of attempts made with the iPhone pupillometer compared with 4% of attempts made with the infrared pupillometer (Fisher's exact p = 0.0001). Method comparison of the two devices used simultaneously showed significant disagreement in dynamic measurements. CONCLUSION: The iPhone pupillometer had poor repeatability and suggests that it is not a practical tool to support clinical decisions.

Intraoperative lidocaine infusion and 24-hour postoperative opioid consumption in obese patients undergoing laparoscopic bariatric surgery.

BACKGROUND: Bariatric surgery is the most effective long-term treatment for obesity. Opioid-sparing anesthesia and multimodal analgesia such as lidocaine infusion have been recommended in these patients to reduce opioid-related complications. However, evidence supporting its use for bariatric surgery population is limited. OBJECTIVE: To investigate whether intraoperative lidocaine infusion is associated with decreasing opioid consumption in laparoscopic bariatric surgery. SETTING: A university hospital, California, USA. METHODS: In this retrospective cohort study, outcomes among consecutive obese patients undergoing laparoscopic bariatric surgery between January 2016 to December 2018 were evaluated to determine the impact of adjunctive intraoperative lidocaine infusion on 24-hour postoperative opioid consumption. Secondary outcomes, including opioid consumption during hospitalization, length of stay, and postoperative complications were determined. Post hoc analyses were performed exploring possible dose effects and drug-drug interactions. Univariable and multivariable analyses were performed to identify factors associated with opioid consumption. RESULTS: Among 345 patients, 54 (15.7%) received intraoperative lidocaine infusion (L+) whereas 291 (84.3%) did not receive intraoperative lidocaine infusion (L-). Both L+ and L- groups shared similar demographic characteristics. The 24-hour postoperative opioid consumption was 17.6% lower in L+ (95% confidence interval -28.4 to -5.2, P = .007), but nonsignificantly lower in the multivariate model (12.8%, 95% confidence interval -24.4 to .5, P = .06). Opioid consumption during hospitalization, length of stay, and other clinically significant outcomes did not differ. However, subgroup analysis restricted to opioid-naïve patients indicated significantly reduced opioid consumption in the L+ group. Post hoc analysis suggested interaction between lidocaine and ketamine in decreasing 24-hour postoperative opioid consumption. CONCLUSIONS: Intraoperative lidocaine infusion was not significantly associated with decreasing 24-hour postoperative opioid consumption in obese patients undergoing laparoscopic bariatric surgery.

Antibiotic prescribing for pediatric respiratory infections: What explains a large variation among physicians?

OBJECTIVE: To explore whether there are observable physician characteristics associated with antibiotic prescribing for pediatric respiratory tract infections (RTIs). DESIGN: Population-based cohort study using a hierarchical generalized linear mixed-model analysis. SETTING: British Columbia. PARTICIPANTS: All pediatric visits for RTIs between 2005 and 2011. MAIN OUTCOME MEASURES: The association between an antibiotic prescription being dispensed within 5 days after each visit and patient, physician, and regional characteristics. RESULTS: Overall, 27.9% of RTI visits were followed by an antibiotic prescription. After accounting for observed patient, physician, and regional factors, median 2-fold variation was found across physicians in their odds of prescribing. Observable physician characteristics explained nearly half of the variation between them. Higher prescribing was evident among physicians with more years of clinical experience (odds ratio [OR] of 1.46, 95% CI 1.33 to 1.61), international medical graduates (OR = 1.73, 95% CI 1.63 to 1.83), and physicians with proportionally fewer recent visits for RTIs (OR = 1.45, 95% CI 1.38 to 1.52). Female physicians prescribed less often than male physicians did (OR 0.91, 95% CI 0.86 to 0.96). CONCLUSION: Substantial variations were found among physicians in prescribing antibiotics for pediatric RTIs. Observable characteristics accounted for a meaningful proportion of this variation; however, some physicians have a higher propensity to prescribe than others do, which remains unexplained. Patient and regional characteristics did not explain much of the variation across physicians. In future, behavioural interventions should be designed and evaluated to target physicians with higher propensity to prescribe.

What can we learn by examining variations in the use of urine culture in the management of acute cystitis? A retrospective cohort study with linked administrative data in British Columbia, Canada, 2005-2011.

INTRODUCTION: Urinary tract infections (UTI) are common community-based bacterial infections. Empiric antibiotic recommendations are guided by local resistance rates. Previous research suggests that cultures are overused for uncomplicated cystitis, but practice patterns have not been described in detail. Variations in culturing have implications for the interpretation of antibiotic resistance rates. METHODS: We used a retrospective cohort study to analyze variations in urine culturing among physicians, controlling for patient and physician characteristics. We identified all outpatient physician visits among adults and children for cystitis in British Columbia between 2005 and 2011 using administrative data and linked these to laboratory data on urine cultures. Using hierarchical generalized linear mixed models we explored variations in urine culture submissions for cystitis (ICD code 595) and the associations with patient and physician characteristics, stratified by patient sex. RESULTS: Urine cultures were associated with 16% of visits for cystitis among females and 9% among males, and 59% of visits overall were associated with antibiotic treatment. Older patients, patients with a recent antibiotic prescription, and long term care residents were significantly less likely to have a culture associated with a cystitis visit, whether male or female. Female physicians and physicians with 16-35 years' experience were more likely to culture, while international medical graduates were less likely-particularly for female visits. Notably, there was substantial unexplained variation among physicians after controlling for physician characteristics: we found a 24-fold variation in the odds of culturing a female UTI between physicians who were otherwise similar. CONCLUSION: Individual physicians show substantial variation in their propensity to submit cultures for cystitis visits. Reducing such variation and encouraging appropriate levels of culturing would support effective antibiotic use.

Pupillary Unrest in Ambient Light and Prediction of Opioid Responsiveness: Case Report on Its Utility in the Management of 2 Patients With Challenging Acute Pain Conditions.

Pupillary unrest in ambient light (PUAL), the normal pattern of pupil diameter fluctuation present in awake humans, has been proposed as a marker of central opioid effect. We report 2 cases in which PUAL identified the appropriate pain management for 2 patients, each with unique, challenging acute pain conditions. In both cases, PUAL accurately predicted opioid responsiveness, suggesting an effective, individualized analgesic approach for both patients.