Proteomics identifies complement protein signatures in patients with alcohol-associated hepatitis.

Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), creating an unmet need to identify noninvasive biomarkers for AH. In murine models, complement contributes to ethanol-induced liver injury. Therefore, we hypothesized that complement proteins could be rational diagnostic/prognostic biomarkers in AH. Here, we performed a comparative analysis of data derived from human hepatic and serum proteome to identify and characterize complement protein signatures in severe AH (sAH). The quantity of multiple complement proteins was perturbed in liver and serum proteome of patients with sAH. Multiple complement proteins differentiated patients with sAH from those with alcohol cirrhosis (AC) or alcohol use disorder (AUD) and healthy controls (HCs). Serum collectin 11 and C1q binding protein were strongly associated with sAH and exhibited good discriminatory performance among patients with sAH, AC, or AUD and HCs. Furthermore, complement component receptor 1-like protein was negatively associated with pro-inflammatory cytokines. Additionally, lower serum MBL associated serine protease 1 and coagulation factor II independently predicted 90-day mortality. In summary, meta-analysis of proteomic profiles from liver and circulation revealed complement protein signatures of sAH, highlighting a complex perturbation of complement and identifying potential diagnostic and prognostic biomarkers for patients with sAH.

Adjustment for Renal Function Improves the Prognostic Performance of Urinary Thromboxane Metabolites.

BACKGROUND: Systemic thromboxane A2 generation, assessed by quantifying the concentration of stable thromboxane B2 metabolites (TXB2-M) in the urine adjusted for urinary creatinine, is strongly associated with mortality risk. We sought to define optimal TXB2-M cutpoints for aspirin users and nonusers and determine if adjusting TXB2-M for estimated glomerular filtration rate (eGFR) in addition to urinary creatinine improved mortality risk assessment. METHODS: Urinary TXB2-M were measured by competitive ELISA in 1363 aspirin users and 1681 nonusers participating in the Framingham Heart Study. Cutpoints were determined for TXB2-M and TXB2-M/eGFR using log-rank statistics and used to assess mortality risk by Cox proportional hazard modeling and restricted mean survival time. Multivariable models were compared using the Akaike Information Criterion (AIC). A cohort of 105 aspirin users with heart failure was used for external validation. RESULTS: Optimized cutpoints of TXB2-M were 1291 and 5609 pg/mg creatinine and of TXB2-M/eGFR were 16.6 and 62.1 filtered prostanoid units (defined as pg·min/creatinine·mL·1.73 m2), for aspirin users and nonusers, respectively. TXB2-M/eGFR cutpoints provided more robust all-cause mortality risk discrimination than TXB2-M cutpoints, with a larger unadjusted hazard ratio (2.88 vs 2.16, AIC P < 0.0001) and greater differences in restricted mean survival time between exposure groups (1.46 vs 1.10 years), findings that were confirmed in the external validation cohort of aspirin users. TXB2-M/eGFR cutpoints also provided better cardiovascular/stroke mortality risk discrimination than TXB2-M cutpoints (unadjusted hazard ratio 3.31 vs 2.13, AIC P < 0.0001). CONCLUSION: Adjustment for eGFR strengthens the association of urinary TXB2-M with long-term mortality risk irrespective of aspirin use.

A liposomal bupivacaine infiltrative block reduces rescue analgesia administration compared to a bupivacaine splash block after canine ovariohysterectomy in a teaching laboratory.

OBJECTIVE: This study aimed to determine whether an infiltrative block with liposomal bupivacaine was associated with less rescue analgesia administration and lower pain scores than a bupivacaine splash block after ovariohysterectomy in dogs. ANIMALS: Eligible dogs included those that were spayed as part of a veterinary teaching laboratory. Dogs were up to 7 years old and otherwise healthy. A total of 136 dogs were analyzed. METHODS: All dogs underwent ovariohysterectomy performed by veterinary students. Dogs received hydromorphone and acepromazine premedication, propofol induction, isoflurane maintenance, and an NSAID. Dogs were randomly allocated to receive either a splash block with standard bupivacaine or an infiltrative block with liposomal bupivacaine for incisional analgesia. Postoperatively, all dogs were assessed by a blinded evaluator using the Colorado State University-Canine Acute Pain Scale (CSU-CAPS) and Glasgow Composite Measures Pain Scale-Short Form (GCPS-SF). Dogs received rescue analgesia with buprenorphine if they scored ≥ 2 on the CSU-CAPS scale. RESULTS: Dogs that received liposomal bupivacaine had a significantly lower incidence of (P = .04) and longer time to (P = .03) administration of rescue analgesia. There was an overall time-averaged significant difference between groups for CSU-CAPS (P = .049) and GCPS-SF scores (P = .015), with dogs in the bupivacaine group being more likely to have an elevated pain score at some point for both scales. CLINICAL RELEVANCE: The use of liposomal bupivacaine in an infiltrative block may decrease the need for rescue analgesia in dogs undergoing ovariohysterectomy compared to a bupivacaine splash block.

Design of a multicenter randomized clinical trial for treatment of Alcohol-Associated Hepatitis.

Background: Mortality is high for severe alcohol-associated hepatitis (AH). Corticosteroids are the standard of care for patients without contraindications. Recent data showed that interleukin-1ß receptor antagonist anakinra attenuated inflammation and liver damage. We designed a multicenter, double-blind, randomized controlled trial to assess the safety and efficacy of anakinra compared to prednisone. Methods: Patients meeting the clinical and biochemical criteria for severe AH with MELD scores between 20 and 35 were recruited at eight clinical sites. Eligible patients enrolled in the study were randomized to anakinra, 100 mg subcutaneous injection for 14 days, plus zinc sulfate 220 mg for 90 days, vs. prednisone 40 mg PO daily for 30 days. Matching placebos for anakinra, zinc, and prednisone were provided to mask the treatment. Participants were followed for 180 days. The primary outcome was overall survival at 90 days. An unadjusted log-rank test was used to compare the survival of the two treatments in the first 90 days. Between July 10, 2020, and March 4, 2022, we screened 1082 patients with severe AH, and 147 eligible patients were enrolled and randomized. The average baseline MELD score was 25 [range 20-35], Maddrey discriminant function (MDF) was 59.4 [range 20.2-197.5]. The mean aspartate transaminase (AST)-to-alanine transaminase (ALT) ratio was 3.5. The baseline characteristics were not statistically different between the two treatment groups. Conclusions: The study provided a direct comparison of the survival benefits and safety profiles of anakinra plus zinc vs. prednisone in patients with severe AH.

Association of Thromboxane Generation With Survival in Aspirin Users and Nonusers.

BACKGROUND: Persistent systemic thromboxane generation, predominantly from nonplatelet sources, in aspirin (ASA) users with cardiovascular disease (CVD) is a mortality risk factor. OBJECTIVES: This study sought to determine the mortality risk associated with systemic thromboxane generation in an unselected population irrespective of ASA use. METHODS: Stable thromboxane B2 metabolites (TXB2-M) were measured by enzyme-linked immunosorbent assay in banked urine from 3,044 participants (mean age 66 ± 9 years, 53.8% women) in the Framingham Heart Study. The association of TXB2-M to survival over a median observation period of 11.9 years (IQR: 10.6-12.7 years) was determined by multivariable modeling. RESULTS: In 1,363 (44.8%) participants taking ASA at the index examination, median TXB2-M were lower than in ASA nonusers (1,147 pg/mg creatinine vs 4,179 pg/mg creatinine; P < 0.0001). TXB2-M were significantly associated with all-cause and cardiovascular mortality irrespective of ASA use (HR: 1.96 and 2.41, respectively; P < 0.0001 for both) for TXB2-M in the highest quartile based on ASA use compared with lower quartiles, and remained significant after adjustment for mortality risk factors for similarly aged individuals (HR: 1.49 and 1.82, respectively; P ≤ 0.005 for both). In 2,353 participants without CVD, TXB2-M were associated with cardiovascular mortality in ASA nonusers (adjusted HR: 3.04; 95% CI: 1.29-7.16) but not in ASA users, while ASA use was associated with all-cause mortality in those with low (adjusted HR: 1.46; 95% CI: 1.14-1.87) but not elevated TXB2-M. CONCLUSIONS: Systemic thromboxane generation is an independent risk factor for all-cause and cardiovascular mortality irrespective of ASA use, and its measurement may be useful for therapy modification, particularly in those without CVD.

Epidemiological and clinical features of Panton-Valentine Leukocidin positive Staphylococcus aureus bacteremia: A case-control study.

BACKGROUND: Panton-Valentine Leukocidin (PVL) toxin in Staphylococcus aureus has been associated with both severe pneumonia and skin and soft tissue infections. However, there are only limited data on how this virulence factor may influence the clinical course or complications of bacteremic S. aureus infections. METHODS: Between September 2016 and March 2018, S. aureus isolates from clinical cultures from hospitals in an academic medical center underwent comprehensive genomic sequencing. Four hundred sixty-nine (29%) of 1681 S. aureus sequenced isolates were identified as containing the genes that encode for PVL. Case patients with one or more positive blood cultures for PVL were randomly matched with control patients having positive blood cultures with lukF/lukS-PV negative (PVL strains from a retrospective chart review). RESULTS: 51 case and 56 control patients were analyzed. Case patients were more likely to have a history of injection drug use, while controls more likely to undergo hemodialysis. Isolates from 78.4% of case patients were methicillin resistant as compared to 28.6% from control patients. Case patients had a higher incidence of pneumonia and skin and soft tissue infection and longer duration of fever without differences in length of bacteremia. Clinical cure or expiration was comparable. CONCLUSIONS: These results are consistent with prior observations associating the PVL toxin with both community-acquired MRSA strains as well as severe staphylococcal pneumonia. The presence of the PVL toxin does not appear to otherwise influence the natural history of bacteremic S. aureus disease other than in prolonging the duration of fever.

AAV gene therapy for Tay-Sachs disease.

Tay-Sachs disease (TSD) is an inherited neurological disorder caused by deficiency of hexosaminidase A (HexA). Here, we describe an adeno-associated virus (AAV) gene therapy expanded-access trial in two patients with infantile TSD (IND 18225) with safety as the primary endpoint and no secondary endpoints. Patient TSD-001 was treated at 30 months with an equimolar mix of AAVrh8-HEXA and AAVrh8-HEXB administered intrathecally (i.t.), with 75% of the total dose (1 × 1014 vector genomes (vg)) in the cisterna magna and 25% at the thoracolumbar junction. Patient TSD-002 was treated at 7 months by combined bilateral thalamic (1.5 × 1012 vg per thalamus) and i.t. infusion (3.9 × 1013 vg). Both patients were immunosuppressed. Injection procedures were well tolerated, with no vector-related adverse events (AEs) to date. Cerebrospinal fluid (CSF) HexA activity increased from baseline and remained stable in both patients. TSD-002 showed disease stabilization by 3 months after injection with ongoing myelination, a temporary deviation from the natural history of infantile TSD, but disease progression was evident at 6 months after treatment. TSD-001 remains seizure-free at 5 years of age on the same anticonvulsant therapy as before therapy. TSD-002 developed anticonvulsant-responsive seizures at 2 years of age. This study provides early safety and proof-of-concept data in humans for treatment of patients with TSD by AAV gene therapy.

Ergocalciferol in New-onset Type 1 Diabetes: A Randomized Controlled Trial.

CONTEXT: The effect of the anti-inflammatory and immunomodulatory actions of vitamin D on the duration of partial clinical remission (PR) in youth with type 1 diabetes (T1D) is unclear. OBJECTIVE: This work aimed to determine the effect of adjunctive ergocalciferol on residual ß-cell function (RBCF) and PR in youth with newly diagnosed T1D who were maintained on a standardized insulin treatment protocol. The hypothesis was that ergocalciferol supplementation increases RBCF and prolongs PR. METHODS: A 12-month, randomized, double-blind, placebo-controlled trial was conducted of 50 000 IU of ergocalciferol per week for 2 months, and then once every 2 weeks for 10 months, vs placebo in 36 individuals aged 10 to 21 years, with T1D of less than 3 months and a stimulated C-peptide (SCP) level greater than or equal to 0.2 nmol/L (≥ 0.6 ng/mL). The ergocalciferol group had 18 randomly assigned participants (10 male/8 female), mean age 13.3 ±â€…2.8 years, while the control group had 18 participants (14 male/4 female), aged 14.3 ±â€…2.9 years. RESULTS: The ergocalciferol treatment group had statistically significantly higher serum 25-hydroxyvitamin D at 6 months (P = .01) and 9 months (P = .02) than the placebo group. At 12 months, the ergocalciferol group had a statistically significantly lower serum tumor necrosis factor α (TNF-α) concentration (P = .03). There were no statistically significant differences between the groups at each time point from baseline to 12 months for SCP concentration (P = .08), glycated hemoglobin A1c (HbA1c) (P = .09), insulin dose-adjusted A1c (IDAA1c), or total daily dose of insulin. Temporal trends for rising HbA1c (P = .04) and IDAA1c (P = .02) were statistically significantly blunted in the ergocalciferol group. CONCLUSION: Ergocalciferol statistically significantly reduced serum TNF-α concentration and the rates of increase both in A1c and IDAA1c, suggesting a protection of RBCF and PR in youth with newly diagnosed T1D.

COVID-19 Pandemic and Pediatric Type 1 Diabetes: No Significant Change in Glycemic Control During The Pandemic Lockdown of 2020.

Importance: There is no consensus on the impact of the 2020 COVID-19 pandemic lockdown on glycemic control in children and adolescents with type 1 diabetes (T1D) in the US. Aim: To determine the impact of the pandemic lockdown of March 15th through July 6th, 2020 on glycemic control after controlling for confounders. Subjects and Methods: An observational study of 110 subjects of mean age 14.8 ± 4.9 years(y), [male 15.4 ± 4.0y, (n=57); female 14.1 ± 3.8y, (n=53), p=0.07] with T1D of 6.31 ± 4.3y (95% CI 1.0-19.7y). Data were collected at 1-4 months before the lockdown and 1-4 months following the lifting of the lockdown at their first post-lockdown clinic visit. Results: There was no significant change in A1c between the pre- and post-pandemic lockdown periods, 0.18 ± 1.2%, (95% CI -0.05 to 0.41), p=0.13. There were equally no significant differences in A1c between the male and female subjects, -0.16 ± 1.2 vs -0.19 ± 1.2%, p=0.8; insulin pump users and non-pump users, -0.25 ± 1.0 vs -0.12 ± 1.4%, p=0.5; and pubertal vs prepubertal subjects, 0.18 ± 1.3 vs -0.11 ± 0.3%, p=0.6. The significant predictors of decrease in A1c were pre-lockdown A1c (p<0.0001) and the use of CGM (p=0.019). The CGM users had significant reductions in point-of-care A1c (0.4 ± 0.6%, p=0.0012), the CGM-estimated A1c (p=0.0076), mean glucose concentration (p=0.022), a significant increase in sensor usage (p=0.012), with no change in total daily dose of insulin (TDDI). The non-CGM users had significantly increased TDDI (p<0.0001) but no change in HbA1c, 0.06 ± 1.8%, p=0.86. Conclusions: There was no change in glycemic control during the pandemic lockdown of 2020 in US children.

Rethinking Farkas: Updating Cephalic Index Norms in a Large, Diverse Population.

BACKGROUND: Cephalic index, the ratio of head width to length, is one normative indicator used by insurers to derive criteria for plagiocephaly helmet authorization. Current norms were established by a small sample of white children in the 1987 Farkas and Munro data set. This study establishes updated cephalic index values for infants and children in a large, diverse patient population. METHODS: Children aged 0 to 3 months, 3 to 6 months, 9 to 12 months, 2 to 3 years, and 12 to 14 years were recruited at their well-child appointment. Cephalic index was calculated for each age group and compared to previously established norms. RESULTS: Eight hundred seventy patients met inclusion criteria. The means for boys and girls between 0 and 6 months were 83.5 (n = 155, SD 6.01) and 83.5 (n = 191, SD 5.80), respectively. Established means for boys and girls between 0 and 6 months were 74.4 (n = 38, SD 5.2) and 74.3 (n = 49, SD 6.1), respectively. The difference between norms is highly statistically significant (p < 0.0001). For this age range, insurance criteria for a helmet is >83.7 for boys and >82.7 for girls. Using previous norms, 74 boys (44.6 percent) and 104 girls (54.5 percent) would meet criteria for a helmet under current guidelines. CONCLUSIONS: The mean cephalic index of children has changed. The reasons could include diversifying populations in the United States and the introduction of the Back to Sleep campaign. Over 50 percent of children may inappropriately meet criteria for a helmet based on prior norms. Updating norms could change the definition of plagiocephaly for a helmet orthosis.

Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.

Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea. Objective: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-ß0 thalassemia, or S-ß+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included. Interventions: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). Main Outcomes and Measures: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup. Results: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%). Conclusions and Relevance: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes. Trial Registration: ClinicalTrials.gov Identifier: NCT01737814.

Representation of Women in Diagnostic Radiology Residency Programs: Does National Institutes of Health Program Ranking Matter?

PURPOSE: Women are consistently underrepresented in the radiology workforce. The authors examined recent trends in the gender distribution of residents entering diagnostic radiology residency programs. METHODS: A retrospective review was performed of residents entering US diagnostic radiology residency programs for graduate medical education years 2009 to 2018. Demographic and program data were obtained from the Association of American Medical Colleges GME Track Resident Survey. National Institutes of Health (NIH) ranking was determined according to the Academy for Radiology & Biomedical Imaging Research. Descriptive statistical analyses were performed to evaluate the gender distribution of residents according to residency program ranking. RESULTS: The final analytic sample included 11,788 residents who entered diagnostic radiology residency programs during the study period, of whom 3,245 (27.5%) were women and 8,543 (72.5%) were men. A higher percentage of female residents entered programs ranked in NIH rank group 1st to 20th (351 of 1,185 [29.6%]) than entered programs that were ranked lower than 20th or were unranked (1,540 of 5,819 [26.5%]; P = .026). CONCLUSIONS: The present findings confirm repeated reports that women are underrepresented in radiology. The results indicate a need for further study on why a greater proportion of female residents are entering programs with higher NIH rankings. Better understanding of factors and interventions that led to this rise in the percentage of women in higher ranked programs provides an opportunity to expand gender diversity across the field of radiology.

Mechanisms and early patterns of dyslipidemia in pediatric type 1 and type 2 diabetes.

Objectives The is no consensus on the early patterns of lipid-based cardiovascular disease (CVD) risk in youth with either type 1 diabetes (T1D) or type 2 diabetes (T2D). The aim was todetermine the differences in CVD risk, using lipid profiles, in children and adolescents with either T1D or T2D at the time of their first lipid assessment, after stratifying the T1D cohort into remitters and non-remitters based on their honeymoon history. Methods A cross-sectional study of 249 subjects consisting of 73 controls, 53 T2D subjects, and 123 T1D subjects stratified into remitters (n=44), and non-remitters (n=79). Partial clinical remission (PCR) was defined as insulin-dose adjusted HbA1c of ≤9. Pubertal status was determined by Tanner staging. Results After adjusting for age, sex, BMI, race, and pubertal status, T2D patients had significantly higher LDL-C compared to the controls (p=0.022), the remitters (p=0.029), but not the non-remitters (103.1 ± 5.9 mg/dL vs. 91.4 ± 4.2 mg/dL, p=0.49). Similarly, T2D patients had significantly higher non-HDL-C compared to the controls (p=0.006), the remitters (p=0.0002), but not the non-remitters (137.6 ± 7.1 mg/dL vs. 111.71 ± 5.0 mg/dL, p=0.053). Total cholesterol was also significantly higher in T2D patients compared to the controls (p=0.0005), the remitters (p=0.006) but not the non-remitters (183.5 ± 6.6 mg/dL vs. 166.2 ± 4.8 mg/dL, p=0.27). Conclusions Lack of the honeymoon phase in children and adolescents with T1D confers early and significantly increased lipid-based cardiovascular risk to these patients that is similar to the elevated cardiovascular risk seen in T2D.

Continuous glucose monitoring reduces pubertal hyperglycemia of type 1 diabetes.

Background Physiologic hyperglycemia of puberty is a major contributor to poor glycemic control in youth with type 1 diabetes (T1D). This study's aim was to determine the effectiveness of continuous glucose monitoring (CGM) to improve glycemic control in pubertal youth with T1D compared to a non-CGM cohort after controlling for age, sex, BMI, duration, and insulin delivery methodology. The hypothesis is that consistent CGM use in puberty improves compliance with diabetes management, leading to increased percentage (%) time in range (TIR70-180 mg/dL) of glycemia, and lowering of HbA1c. Methods A longitudinal, retrospective, case-controlled study of 105 subjects consisting of 51 T1D controls (60.8% male) age 11.5 ± 3.8 y; and 54 T1D subjects (48.1% male) age 11.1 ± 5.0 y with confirmed CGM use for 12 months. Pubertal status was determined by Tanner staging. Results were adjusted for baseline HbA1c and diabetes duration. Results HbA1c was similar between the controls and the CGM group at baseline: 8.2 ± 1.1% vs 8.3 ± 1.2%, p=0.48 respectively; but was significantly lower in the CGM group 12 months later, 8.2 ± 1.1% vs. 8.7 ± 1.4%, p=0.035. Longitudinal change in HbA1c was similar in the prepubertal cohort between the control- and CGM groups: -0.17 ± 0.98% vs. 0.38 ± 1.5%, p=0.17. In contrast, HbA1c increased with advancing age and pubertal status in the pubertal controls but not in the pubertal CGM group: 0.55 ± 1.4 vs -0.22 ± 1.1%, p=0.020. Percent TIR was inversely related to HbA1c in the CGM group, r=-0.6, p=0.0004, for both prepubertal and pubertal subjects. Conclusions CGM use significantly improved glycemic control in pubertal youth with T1D compared to non-CGM users.

Teamwork for smoking cessation: which smoker was willing to engage their partner? Results from a cross-sectional study.

OBJECTIVE: Smokers are greatly influenced by those living with them, but strategies that increase partner support for smoking cessation are lacking. Using a cross-sectional study design, we explored factors associated with willingness to engage a partner in smoking cessation in smokers registered on a web-assisted tobacco intervention trial. RESULTS: Study participants (n = 983) were recruited between July 2018 and March 2019. About 28% of smokers were willing to engage their partner in cessation efforts. The odds of willingness to engage a partner were more than two-fold for smokers reporting presence of other smokers in the immediate family (adjusted odds ratio (aOR): 2.18; 95% confidence interval (CI) 1.51-3.15 for 1-3 smokers; aOR, 3.12; 95% CI 1.95-4.98 for ≥ 4 smokers) compared to those with no smokers in the immediate family. Women had lower odds of willingness to engage (aOR; 0.82; 95% CI 0.58-1.16) than men, but this was not statistically significant. Use of e-cigarettes and visitation to a smoking cessation website prior to the intervention were both positively associated with willingness to engage partners in cessation. Future research should assess whether interventions tailored to smokers willing to engage partners or spouses could increase effectiveness of partner support during cessation.

Comparison of liposomal bupivacaine and 0.5% bupivacaine hydrochloride for control of postoperative pain in dogs undergoing tibial plateau leveling osteotomy.

OBJECTIVE: To compare liposome-encapsulated bupivacaine (LEB) and (nonliposomal) 0.5% bupivacaine hydrochloride (0.5BH) for control of postoperative pain in dogs undergoing tibial plateau leveling osteotomy (TPLO). ANIMALS: 33 client-owned dogs. PROCEDURES: In a randomized clinical trial, dogs undergoing TPLO received LEB (5.3 mg/kg [2.4 mg/lb]) or 0.5BH (1.5 mg/kg [0.68 mg/lb]) by periarticular soft tissue injection. All dogs received carprofen (2.2 mg/kg [1 mg/lb], SC, q 12 h) beginning at extubation. Signs of pain were assessed at extubation and predetermined times up to 48 hours later with the Colorado State University-Canine Acute Pain Scale and Glasgow Composite Pain Scale-Short Form. A pressure nociceptive threshold device was used at the affected stifle joint before surgery and at 5 postoperative time points. Methadone (0.1 mg/kg [0.05 mg/lb], IV) was administered if the Colorado State University pain scale score was ≥ 2 (scale, 0 to 4). Surgical variables; pain scores; pressure nociceptive thresholds; times to first administration of rescue analgesic, first walk, and first meal consumption; and total opioid administration were compared between treatment groups. RESULTS: 28 dogs completed the study. Dogs administered LEB were less likely to require rescue analgesia and received lower amounts of opioids than dogs administered 0.5BH. There were no significant intergroup differences in other measured variables. CONCLUSIONS AND CLINICAL RELEVANCE: The LEB appeared to provide adequate analgesia after TPLO with lower requirements for opioid treatments, which may allow dogs to be discharged from the hospital earlier than with traditional pain management strategies.

Design, analysis, power, and sample size calculation for three-phase interrupted time series analysis in evaluation of health policy interventions.

OBJECTIVE: To discuss the study design and data analysis for three-phase interrupted time series (ITS) studies to evaluate the impact of health policy, systems, or environmental interventions. Simulation methods are used to conduct power and sample size calculation for these studies. METHODS: We consider the design and analysis of three-phase ITS studies using a study funded by National Institutes of Health as an exemplar. The design and analysis of both one-arm and two-arm three-phase ITS studies are introduced. RESULTS: A simulation-based approach, with ready-to-use computer programs, was developed to determine the power for two types of three-phase ITS studies. Simulations were conducted to estimate the power of segmented autoregressive (AR) error models when autocorrelation ranged from -0.9 to 0.9 with various effect sizes. The power increased as the sample size or the effect size increased. The power to detect the same effect sizes varied largely, depending on testing level change, trend changes, or both. CONCLUSION: This article provides a convenient tool for investigators to generate sample sizes to ensure sufficient statistical power when three-phase ITS study design is implemented.

Paramedian incisional complications after prophylactic laparoscopy-assisted gastropexy in 411 dogs.

OBJECTIVE: To determine the frequency and types of paramedian incisional complications after prophylactic laparoscopy-assisted gastropexy (LAG) in dogs and to evaluate potential risk factors for complications. STUDY DESIGN: Multi-institutional retrospective study. ANIMALS: Client-owned dogs (N = 411). METHODS: Records for dogs that underwent single-incision-port laparoscopy-assisted gastropexy (SIPLAG) or multiple-port laparoscopy-assisted gastropexy (MPLAG) at five veterinary referral hospitals were reviewed. Information regarding signalment, surgical procedures, perioperative care, and incisional complications was collected. Follow-up information was obtained by review of medical records and/or communication with owners. Potential risk factors for complications were examined statistically. RESULTS: Paramedian incisional complications were observed in 78 of 411 (19%) dogs. The most common complication was seroma formation, which occurred in 51 (12.4%) dogs. Surgical site infections were observed in 16 (3.9%) dogs, and dehiscence or development of excessive scar tissue at the incision site were each observed in nine (2.2%) dogs. Complications resolved with conservative treatment in 75 of 78 (96.2%) dogs and with surgical treatment in three of 78 (3.8%) dogs. The odds of complications were approximately twice as high in dogs undergoing SIPLAG than in dogs undergoing MPLAG (odds ratio, 2.03; P = .006). CONCLUSION: Minor paramedian incisional complications, particularly seroma formation, were frequently observed after LAG. Most complications were successfully managed conservatively. Single-incision-port laparoscopy-assisted gastropexy was associated with a higher complication rate compared with MPLAG. CLINICAL SIGNIFICANCE: Owners should be informed that there is a relatively high rate of minor paramedian incisional complications after LAG. The risk of complications appears to be higher for SIPLAG than for MPLAG.

Simulation-based power and sample size calculation for designing interrupted time series analyses of count outcomes in evaluation of health policy interventions.

OBJECTIVE: The purpose of this study was to present the design, model, and data analysis of an interrupted time series (ITS) model applied to evaluate the impact of health policy, systems, or environmental interventions using count outcomes. Simulation methods were used to conduct power and sample size calculations for these studies. METHODS: We proposed the models and analyses of ITS designs for count outcomes using the Strengthening Translational Research in Diverse Enrollment (STRIDE) study as an example. The models we used were observation-driven models, which bundle a lagged term on the conditional mean of the outcome for a time series of count outcomes. RESULTS: A simulation-based approach with ready-to-use computer programs was developed to calculate the sample size and power of two types of ITS models, Poisson and negative binomial, for count outcomes. Simulations were conducted to estimate the power of segmented autoregressive (AR) error models when autocorrelation ranged from -0.9 to 0.9, with various effect sizes. The power to detect the same magnitude of parameters varied largely, depending on the testing level change, the trend change, or both. The relationships between power and sample size and the values of the parameters were different between the two models. CONCLUSION: This article provides a convenient tool to allow investigators to generate sample sizes that will ensure sufficient statistical power when the ITS study design of count outcomes is implemented.

Postoperative thrombocytosis and thromboelastographic evidence of hypercoagulability in dogs undergoing splenectomy for splenic masses.

OBJECTIVE: To determine the frequency and severity of thrombocytosis and thromboelastographic evidence of hypercoagulability during the first 2 weeks after splenectomy in dogs with splenic masses and to investigate relationships between platelet counts and thromboelastography values. ANIMALS: 34 dogs undergoing splenectomy for splenic masses. PROCEDURES: Blood samples for platelet counts and thromboelastography were obtained at induction of anesthesia (day 0) prior to splenectomy and on days 2, 7, and 14. RESULTS: Mean platelet counts were 167.9 × 103/µL, 260.4 × 103 µ/L, 715.9 × 103/µL, and 582.2 × 103/µL on days 0, 2, 7, and 14, respectively, and were significantly higher at all postoperative assessment points than on day 0. Thrombocytosis was observed in 3% (1/34), 6% (2/33), 81% (21/26), and 69% (18/26) of dogs on days 0, 2, 7, and 14. Platelet counts > 1,000 × 103/µL were observed in 1 dog on day 2 and in 5 dogs on day 7. One or more thromboelastography values suggestive of hypercoagulability were observed in 45% (15/33), 84% (26/31), 89% (24/27), and 84% (21/25) of dogs on days 0, 2, 7, and 14. At each assessment point, higher platelet counts were correlated with thromboelastography values suggestive of hypercoagulability. CONCLUSIONS AND CLINICAL RELEVANCE: Marked thrombocytosis and thromboelastography values suggestive of hypercoagulability were common during the first 2 weeks after splenectomy for the dogs of this study. If present, hypercoagulability could increase the risk for development of postsplenectomy thrombotic conditions such as portal system thrombosis and pulmonary thromboembolism.