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Background: Anterior humeral avulsions of the glenohumeral ligament (aHAGL) lesions are relatively rare causes of shoulder instability that affect athletes at a higher rate than other populations. The purpose of this study is to evaluate rate of return to sport (RTS) after HAGL repair. Methods: A search of the PubMed (MEDLINE), Scopus, and Cochrane CENTRAL databases was conducted on April 13, 2022 with the search terms "HAGL" or "humeral avulsion glenohumeral ligament" was used to conduct the systematic review. Inclusion criteria required that lesions were limited to aHAGL, axillary pouch or central HAGL, or both anterior and posterior HAGL lesions as specified by lesion description or direction of instability. Results: Screening and full-text manuscript review identified 7/967 studies eligible for inclusion with a total of 46 aHAGL lesions in athletes. Average rate of RTS was 93.5% (standard deviation [SD] = 13.4%, n = 43/46) with rate of RTS at previous levels of play averaging 80.0% (SD = 22.1%, n = 28/35). Neither rates of concomitant procedures nor concomitant pathology were associated with variation in RTS rates overall or level of RTS. Weighted average Rowe, subjective shoulder value, and Constant scores were 87.5 (SD = 4.9), 86.0 (SD = 2.0), and 82.2 (SD = 5.1), respectively, and 78.6% (n = 22/28) of patients reported postoperative satisfaction or "good/excellent" ratings following aHAGL repair. Adverse events occurred in 18.5% of patients (n = 10/54), most frequently recurrent instability (n = 3/54). Ultimately, 6.2% of patients eventually underwent reoperation (n = 3/17). Conclusion: As with other forms of anterior shoulder instability, RTS rates after aHAGL repair are high and many patients achieve their previous level of play. The most frequent adverse event was subjective recurrent instability with reoperation in 6.2% of patients. The findings from this study provide valuable pooled data on outcomes specific to aHAGL repair, particularly in the athlete population, and contribute to further understanding of outcomes regarding operative management of this rare pathology.
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Current strategies to understand the molecular basis of Marek's disease virus (MDV) virulence primarily consist of cataloging divergent nucleotides between strains with different phenotypes. However, most comparative genomic studies of MDV rely on previously published consensus genomes despite the confirmed existence of MDV strains as mixed viral populations. To assess the reliability of interstrain genomic comparisons relying on published consensus genomes of MDV, we obtained two additional consensus genomes of vaccine strain CVI988 (Rispens) and two additional consensus genomes of the very virulent strain Md5 by sequencing viral stocks and cultured field isolates. In conjunction with the published genomes of CVI988 and Md5, this allowed us to perform three-way comparisons between multiple consensus genomes of the same strain. We found that consensus genomes of CVI988 can vary in as many as 236 positions involving 13 open reading frames (ORFs). By contrast, we found that Md5 genomes varied only in 11 positions involving a single ORF. Notably, we were able to identify 3 single-nucleotide polymorphisms (SNPs) in the unique long region and 16 SNPs in the unique short (US) region of CVI988GenBank.BAC that were not present in either CVI988Pirbright.lab or CVI988USDA.PA.field. Recombination analyses of field strains previously described as natural recombinants of CVI988 yielded no evidence of crossover events in the US region when either CVI988Pirbright.lab or CVI988USDA.PA.field were used to represent CVI988 instead of CVI988GenBank.BAC. We were also able to confirm that both CVI988 and Md5 populations were mixed, exhibiting a total of 29 and 27 high-confidence minor variant positions, respectively. However, we did not find any evidence of minor variants in the positions corresponding to the 19 SNPs in the unique regions of CVI988GenBank.BAC. Taken together, our findings suggest that continued reliance on the same published consensus genome of CVI988 may have led to an overestimation of genomic divergence between CVI988 and virulent strains and that multiple consensus genomes per strain may be necessary to ensure the accuracy of interstrain genomic comparisons.
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AIMS: In October 2023, the Tennessee Department of Health identified an outbreak of Shiga toxin-producing Escherichia coli (STEC) O157:H7 infections among elementary school students who attended school field trips to the same farm animal exhibit. Our aim was to determine STEC source and prevent additional illnesses by initiating epidemiologic, laboratory and environmental investigations. METHODS AND RESULTS: We identified cases using laboratory-based surveillance and by surveying caregivers of children who attended the exhibit. Probable cases were defined as illness with abdominal cramps or diarrhoea after attendance; confirmed cases were laboratory-confirmed STEC infection in an attendee or household contact. A site visit was conducted, and event organizers were interviewed. Human stool, animal faeces and environmental samples were tested for STEC O157:H7 by real-time polymerase chain reaction (PCR), culture and whole-genome sequencing (WGS). Approximately 2300 elementary school students attended the animal exhibit during 2 days. Field trip activities included contact with different farm animal species, drinking pasteurized milk outside animal enclosures and eating lunch in a separate building onsite. We received survey responses from 399 caregivers for 443 (19%) animal exhibit attendees. We identified 9 confirmed and 55 probable cases with illness onset dates during 26 September to 12 October. Seven children aged 1-7 years were hospitalized. Four children aged 1-6 years experienced haemolytic uraemic syndrome; none died. Laboratory testing identified STEC O157:H7 by culture from eight human stool samples with 0-1 allele difference by WGS. Three environmental samples had Shiga toxin (stx 2) genes detected by PCR, but no STEC isolates were recovered by culture. CONCLUSIONS: This is the largest reported STEC O157:H7 outbreak associated with an animal exhibit in Tennessee. We identified opportunities for educating school staff, event organizers and families about zoonotic disease risks associated with animal contact and published prevention measures.
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The purpose of this systematic review is to describe the pathoanatomy, presentation, diagnostic workup, treatment modalities, and outcomes of posterior interosseous nerve (PIN) palsy in patients with rheumatoid arthritis (RA). All reported cases of PIN palsy in patients with RA were reviewed to yield 72 cases of PIN palsy in 70 patients. The male-to-female ratio was 1:2.7. Pain involving the elbow was very common (20/33 cases reporting this information), and paralysis or weakness of digit extension was noted in 27/33 cases and 6/33 cases, respectively. Only 1 of the 54 cases undergoing surgical intervention reported persistent weakness, and this 1 patient had undergone a 3-month trial of conservative management. In conclusion, Appropriate pharmacologic management in conjunction with magnetic resonance imaging (MRI) and ultrasound monitoring may be used for conservative management, but surgical decompression should still be utilized for patients with a compressive disease pathology who fail to improve with 6 weeks of conservative treatment, or for those with advanced disease on initial presentation.
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Previous research has reported diverging patterns of results with respect to discriminability and response bias when comparing the simultaneous lineup to two different lineup procedures in which items are presented sequentially, the sequential stopping rule lineup and the UK lineup. In a single large sample experiment, we compared discriminability and response bias in six-item photographic lineups presented either simultaneously, sequentially with a stopping rule, or sequentially requiring two full laps through the items before making an identification and including the ability to revisit items, analogous to the UK lineup procedure. Discriminability was greater for the simultaneous lineup compared to the sequential stopping rule lineup, despite a non-significant difference in empirical discriminability between the procedures. There was no significant difference in discriminability when comparing the simultaneous lineup to the sequential two lineup and the sequential two lap lineup to the sequential stopping rule lineup. Responding was most lenient for the sequential two lap lineup, followed by the simultaneous lineup, followed by the sequential lineup. These results imply that sequential item presentation may not exert a large effect in isolation on discriminability and response bias. Rather, discriminability and response bias in the sequential stopping rule lineup and UK lineup result from the interaction of sequential item presentation with other aspects of these procedures.
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Police , Humans , Male , Female , Adult , Young Adult , Discrimination, Psychological/physiology , Reaction Time/physiologyABSTRACT
OBJECTIVE: Acute gastroenteritis (AGE) is the second leading cause of death in children worldwide. Objectively evaluating disease severity is critical for assessing future interventions. We used data from a large, prospective surveillance study to assess risk factors associated with severe presentation using modified Vesikari score (MVS) and Clark score (CS) of severity. METHODS: From December 1, 2012 to June 30, 2016, AGE surveillance was performed for children between 15 days and 17 years old in the emergency, inpatient, and outpatient settings at Vanderbilt's Monroe Carell Jr. Children's Hospital in Nashville, TN. Stool specimens were tested for norovirus, sapovirus, rotavirus, and astrovirus. We compared demographic and clinical characteristics, along with the MVS and CS, by viral detection status and by setting. RESULTS: Of the 6309 eligible children, 4216 (67%) were enrolled, with 3256 (77%) providing a stool specimen. The median age was 1.9 years, 52% were male, and 1387 (43%) of the stool samples were virus positive. Younger age, male sex, hospitalization, and rotavirus detection were significantly associated with higher mean MVS and CS. Non-Hispanic Black race and ethnicity was associated with a lower mean MVS and CS as compared with non-Hispanic white race and ethnicity. Prematurity and enrollment in the ED were associated with higher mean CS. The 2 scoring systems were highly correlated. CONCLUSIONS: Rotavirus continues to be associated with more severe pediatric illness compared with other viral causes of AGE. MVS and CS systems yielded comparable results and can be useful tools to assess AGE severity.
Subject(s)
Gastroenteritis , Severity of Illness Index , Humans , Gastroenteritis/virology , Gastroenteritis/diagnosis , Gastroenteritis/epidemiology , Male , Infant , Female , Child, Preschool , Prospective Studies , Child , Acute Disease , Infant, Newborn , Adolescent , Feces/virology , Risk FactorsABSTRACT
Background Elbows are one of the most frequently dislocated large joints; however, there is limited epidemiological data, especially during the coronavirus disease 2019 (COVID-19) pandemic. This study characterizes elbow dislocations presenting to Emergency Departments (EDs) over the last decade. Methods This study is a cross-sectional, descriptive, epidemiologic analysis of isolated elbow dislocations presenting to EDs from 2011-2020 using the National Electronic Injury Surveillance System (NEISS) database. Patients under 10, those with radial head subluxation, and those with complex fractures were excluded. Data on incidence ratios, patient demographics, mechanisms of injury, and incident locales were analyzed. Results Approximately 83,996 simple, primary elbow dislocations occurred from 2011-2020 (n=2,328), generating an incidence of 2.98/100,000 person-years. Incidence was higher among males (3.26 versus 2.69/100,000 person-years). Dislocations peaked in patients aged 10-19, with higher rates in males (11.12 versus 5.31/100,000 person-years; injury rate ratio 2.09, CI=2.05-2.14, p<0.001). Rates of elbow dislocations decreased with age in males (age 20-29=11.12, age >80=0.63/100,000) but increased in females over 40 (age 40-49=1.59, age 70-79=2.83/100,000). Athletic activities accounted for 55% of dislocations (n=45,902), with 15% from football and 14% from wrestling. The fewest annual dislocations occurred during COVID-19 (n=6440). Injuries occurring at schools and during contact and indoor sports decreased, while those from soccer increased. Conclusions Elbow dislocations are common, with trends of decreasing incidence with age among men and increasing incidence in women over 40. COVID-19 impacted sports-related and epidemiologic injury patterns. Ultimately, understanding population-level risks for elbow dislocations enables orthopaedic surgeons to predict injury trends and conceive educational preventative measures.
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Background: Given the rising prevalence of obesity, the number of patients with obesity undergoing arthroscopic rotator cuff repair (RCR) will likely increase; however, there have been mixed results in the existing literature with regard to the effect of elevated body mass index (BMI) on functional outcomes and complications. Methods: The patient-reported outcome measures included the visual analog scale (VAS) pain score, the American Shoulder and Elbow Surgeons (ASES) score, range of motion, and adverse events. Results: Fourteen studies (118,331 patients) were included. There were significant decreases in VAS pain scores for both patients with obesity (mean difference, -3.8 [95% confidence interval (CI), -3.9 to -3.7]; p < 0.001) and patients without obesity (mean difference, -3.2 [95% CI, -3.3 to -3.1]; p < 0.001). There were also significant increases in ASES scores for both patients with obesity (mean difference, 24.3 [95% CI, 22.5 to 26.1]; p < 0.001) and patients without obesity (mean difference, 24.3 [95% CI, 21.4 to 26.0]; p < 0.001). There were also significant increases in ASES scores for both patients with obesity (mean difference, 24.3 [95% CI, 22.5 to 26.1]; p < 0.001) and patients without obesity (mean difference, 24.3 [95% CI, 21.4 to 26.0]; p < 0.001). However, there were no significant differences in final VAS pain scores, ASES scores, or range of motion between the groups. The mean rates of complications were higher among patients with obesity (1.2% ± 1.7%) than among patients without obesity (0.59% ± 0.11%) (p < 0.0001), and the mean rates of postoperative admissions were also higher among patients with obesity (5.9%) than patients without obesity (3.7%) (p < 0.0001). Although the mean rates of reoperation were similar between groups (5.2% ± 2.8% compared with 5.2% ± 4.2%), the meta-analysis revealed lower odds of reoperation in patients without obesity (odds ratio [OR], 0.76 [95% CI, 0.71 to 0.82]). Conclusions: No significant or clinically important differences in postoperative pain, ASES scores, or range of motion were found between patients with and without obesity following arthroscopic RCR. However, populations with obesity had higher rates of complications, postoperative admissions, and reoperation following arthroscopic RCR. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
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Background: Respiratory syncytial virus (RSV) can cause hospitalization in young children and older adults. With vaccines and monoclonal antibody prophylaxis increasingly available, identifying social factors associated with severe illnesses can guide mitigation efforts. Methods: Using data collected by the RSV Hospitalization Surveillance Network from 2016 to 2023, we identified RSV hospitalizations in Tennessee. We linked hospitalization information (eg, patient demographic characteristics and outcome) with population-level variables (eg, social vulnerability and health care insurance coverage) from publicly available data sets using census tract of residence. Hospitalization incidence was calculated and stratified by period (2016-2020 and 2020-2023). We modeled social vulnerability effect on hospitalization incidence using Poisson regression. Results: Among 2687 RSV hospitalizations, there were 677 (25.2%) intensive care unit admissions and 38 (1.4%) deaths. The highest RSV hospitalization incidences occurred among children aged <5 years and adults aged ≥65 years: 272.8 per 100 000 person-years (95% CI, 258.6-287.0) and 60.6 (95% CI, 56.0-65.2), respectively. Having public health insurance was associated with higher hospitalization incidence as compared with not having public insurance: 60.5 per 100 000 person-years (95% CI, 57.6-63.4) vs 14.3 (95% CI, 13.4-15.2). Higher hospitalization incidence was associated with residing in a census tract in the most socially vulnerable quartile vs the least vulnerable quartile after adjusting for age, sex, and period (incidence rate ratio, 1.4; 95% CI, 1.3-1.6). Conclusions: RSV hospitalization was associated with living in more socially vulnerable census tracts. Population measures of social vulnerability might help guide mitigation strategies, including vaccine and monoclonal antibody promotion and provision to reduce RSV hospitalization.
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Background: While concomitant rotator cuff and inferior labral tears are relatively uncommon in young civilians, military populations represent a unique opportunity to study this injury pattern. Purpose: To (1) evaluate the long-term outcomes after combined arthroscopic rotator cuff and inferior labral repair in military patients <40 years and (2) compare functional outcomes with those after isolated arthroscopic rotator cuff repair. Study Design: Cohort study; Level of evidence, 3. Methods: Military patients who underwent arthroscopic rotator cuff repair between January 2011 and December 2016 and had a minimum of 5-year follow-up data were included in this study. The patients were categorized into those who had undergone combined arthroscopic rotator cuff and inferior labral repair (RCIL cohort) and those who had isolated arthroscopic rotator cuff repair (ARCR cohort). Pre- and postoperative outcome measures-visual analog scale for pain, Single Assessment Numeric Evaluation, American Shoulder and Elbow Surgeons shoulder score, Rowe Instability Score, and range of motion-were compared between the groups. Results: A total of 50 shoulders (27 in the RCIL cohort and 23 in the ARCR cohort) were assessed. The RCIL and ARCR groups were similar in terms of age (mean, 33.19 years [range, 21-39 years] vs 35.39 years [range, 26-39 years], respectively) and sex (% male, 88.46% vs 82.61%, respectively). All patients were active-duty military at the time of surgery. The mean final follow-up was at 106.93 ± 16.66 months for the RCIL group and 105.70 ± 7.52 months for the ARCR group (P = .75). There were no differences in preoperative outcome scores between groups. Postoperatively, both groups experienced statistically significant improvements in all outcome scores (P < .0001 for all), and there were no significant group differences in any final postoperative outcome measures. At the final follow-up, 26 (96.30%) patients in the RCIL cohort and 20 (86.96%) in the ARCR cohort had returned to unrestricted active-duty military service (P = .3223). Conclusion: The study findings indicate that concomitant glenohumeral stabilization does not prevent worse outcomes after arthroscopic rotator cuff repair in this military cohort. Combined repair produced statistically and clinically significant improvements in outcome scores at the long-term follow-up, indicating that simultaneous repair of combined lesions was an appropriate treatment option in this patient population.
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Syndromic polymerase chain reaction (PCR) panels are used to test for pathogens that can cause rash illnesses, including measles. Rash illnesses have infectious and noninfectious causes, and approximately 5% of persons experience a rash 7-10 days after receipt of a measles, mumps, and rubella (MMR) vaccine. MMR vaccine includes live attenuated measles virus, which is detectable by PCR tests. No evidence exists of person-to-person transmission of measles vaccine virus, and illness does not typically result among immunocompetent persons. During September 2022-January 2023, the Tennessee Department of Health received two reports of measles detected by syndromic PCR panels. Both reports involved children (aged 1 and 6 years) without known risk factors for measles, who were evaluated for rash that occurred 11-13 days after routine MMR vaccination. After public health responses in Tennessee determined that both PCR panels had detected measles vaccine virus, six state health departments collaborated to assess the frequency and characteristics of persons receiving a positive measles PCR panel test result in the United States. Information was retrospectively collected from a commercial laboratory testing for measles in syndromic multiplex PCR panels. During May 2022-April 2023, among 1,548 syndromic PCR panels, 17 (1.1%) returned positive test results for measles virus. Among 14 persons who received a positive test result and for whom vaccination and case investigation information were available, all had received MMR vaccine a median of 12 days before specimen collection, and none had known risk factors for acquiring measles. All positive PCR results were attributed to detection of measles vaccine virus. Increased awareness among health care providers about potential measles detection by PCR after vaccination is needed. Any detection of measles virus by syndromic PCR testing should be immediately reported to public health agencies, which can use measles vaccination history and assessment of risk factors to determine the appropriate public health response. If a person recently received MMR vaccine and has no risk factors for acquiring measles, additional public health response is likely unnecessary.
Subject(s)
Exanthema , Measles , Mumps , Rubella , Child , Humans , United States/epidemiology , Infant , Measles-Mumps-Rubella Vaccine , Retrospective Studies , Measles/diagnosis , Measles/epidemiology , Measles/prevention & control , Measles virus/genetics , Mumps/prevention & control , Vaccination , Tennessee/epidemiology , Polymerase Chain Reaction , Rubella/prevention & control , Antibodies, ViralABSTRACT
BACKGROUND: Advances in total hip arthroplasty (THA) have resulted in evolving revision indications and intraoperative techniques, which can influence the exposure of trainees to complex cases. We report 3 decades of revision experience from a tertiary referral center that trains fellows, comparing the reasons for revision and the complexity of revisions over time. METHODS: We retrospectively reviewed all revision THAs performed at our institution from 1990 to 2022. Revision diagnoses, components revised, types of revision implants used, and exposure techniques were collected. A "complex" revision was defined as a case that involved an extended trochanteric osteotomy, triflange and cup-cage construct, or acetabular augment. RESULTS: A total of 3,556 THA revisions were identified (108 revisions/year). Aseptic loosening was the most common indication in 1990 to 1999 (45 per year), but decreased to 28.3/year in 2010 to 2019. From 1990 to 1999 and 2010 to 2019, fracture increased from 3.1 to 7.3 per year, infection from 2.9/year to 16.9/year, and metallosis from 0.1 to 13.2 per year. Both component revision were common from 1990 to 1994 (42.6 per year), while polyethylene exchange was most common in 2010 to 2019 (43.3 per year). A decrease was observed in "complex" cases over time: 14.8 extended trochanteric osteotomies/year in 2000 to 2004 compared to 5.4 per year in 2018 to 2022, 4.5 triflange and cup-cage constructs/year in 2004 to 2007 compared to 0.8 per year in 2018 to 2022, and 4 acetabular augments per year in 2009 to 2012 compared to 1 per year in 2018 to 2022. CONCLUSIONS: Indications for revision have changed over the decades, while the number of "complex" revisions has gradually decreased, presumably due to advances in implants and materials. If this trend extends to other training institutions, the next generation of arthroplasty surgeons will have less exposure to complex revisions during their training.
Subject(s)
Arthroplasty, Replacement, Hip , Awards and Prizes , Prosthesis Failure , Reoperation , Humans , Reoperation/statistics & numerical data , Retrospective Studies , Male , Female , Hip Prosthesis , Middle Aged , AgedABSTRACT
Loftus (1978) highlighted the distinction between a theoretical concept such as memory or attention, and its observed measure such as hit rate or percent correct. If the functional relationship between the concept and its measure is nonlinear then only some interaction effects are interpretable. This is an example of the wider "problem of coordination" which pervades scientific measurement. Loftus drew on the principles of additive conjoint measurement (ACM) to discuss the consequences when the coordination function is assumed to be monotonic. This led to the distinction between removable interactions that are consistent with an additive effect on the underlying theoretical concept and nonremovable interactions that are not. However, the adoption of these ideas by researchers has been greatly limited by the fact that no statistical procedure exists to determine if and to what extent an interaction is removable or otherwise. The lack of such a procedure has similarly limited the impact of ACM on research practice. The aim of this article is to present such a procedure. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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This commentary argues against the indictment of current experimental practices such as piecemeal testing, and the proposed integrated experiment design (IED) approach, which we see as yet another attempt at automating scientific thinking. We identify a number of undesirable features of IED that lead us to believe that its broad application will hinder scientific progress.
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Research DesignABSTRACT
OBJECTIVES: Mpox surveillance was integral during the 2022 outbreak response. We evaluated implementation of mpox surveillance in Tennessee during an outbreak response and made recommendations for surveillance during emerging infectious disease outbreaks. METHODS: To understand surveillance implementation, system processes, and areas for improvement, we conducted 8 semistructured focus groups and 7 interviews with 36 health care, laboratory, and health department representatives during September 9-20, 2022. We categorized and analyzed session transcription and notes. We analyzed completeness and timeliness of surveillance data, including 349 orthopoxvirus-positive laboratory reports from commercial, public health, and health system laboratories during July 1-August 31, 2022. RESULTS: Participants described an evolving system and noted that existing informatics platforms inefficiently supported iterations of reporting requirements. Clear communication, standardization of terminology, and shared, adaptable, and user-friendly informatics platforms were prioritized for future emerging infectious disease surveillance systems. Laboratory-reported epidemiologic information was often incomplete; only 55% (191 of 349) of reports included patient address and telephone number. The median time from symptom onset to specimen collection was 5 days (IQR, 3-6 d), from specimen collection to laboratory reporting was 3 days (IQR, 1-4 d), from laboratory reporting to patient interview was 1 day (IQR, 1-3 d), and from symptom onset to patient interview was 9 days (IQR, 7-12 d). CONCLUSIONS: Future emerging infectious disease responses would benefit from standardized surveillance approaches that facilitate rapid implementation. Closer collaboration among informatics, laboratory, and clinical partners across jurisdictions and agencies in determining system priorities and designing workflow processes could improve flexibility of the surveillance platform and completeness and timeliness of laboratory reporting. Improved timeliness will facilitate public health response and intervention, thereby mitigating morbidity.
Subject(s)
Disease Outbreaks , Tennessee/epidemiology , Humans , Disease Outbreaks/prevention & control , Focus Groups , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/prevention & control , Population Surveillance/methods , Public Health Surveillance/methodsABSTRACT
Smallpox was eradicated in 1980 but remains a biothreat due to the potential release of variola virus into the general population. Brincidofovir, the second medicine approved by the US Food and Drug Administration to treat smallpox, is metabolized by oxidative and hydrolytic pathways. The oxidative pathway is initiated by cytochrome P450 4F2 (CYP4F2), an enzyme lacking clinical probes for drug interaction studies. The aim of this work was to assess the impact of reduced activity CYP4F2 variants (rs2108622, C/T and T/T) on brincidofovir pharmacokinetics as a surrogate for drug inhibition. Genotyping was performed on blood from healthy participants receiving oral (n = 261) and intravenous (IV, n = 49) brincidofovir across 6 phase 1 trials. Plasma concentrations were measured by validated liquid chromatography tandem mass spectrometry methods. After oral administration, subjects with the lowest activity CYP4F2 genotype (T/T) had up to 36% higher AUCinf and 29% higher Cmax while subjects with the moderate activity CYP4F2 genotype (C/T) had similar Cmax and AUCinf compared to those with the wild-type genotype. Little to no increase in brincidofovir exposure parameters was observed following IV administration. Based on the lack of significant increases in brincidofovir plasma concentrations in subjects with low activity CYP4F2, a clinically meaningful drug-drug interaction is not expected with CYP4F2 inhibitor and brincidofovir coadministration.
Subject(s)
Cytosine/analogs & derivatives , Organophosphonates , Smallpox , United States , Humans , Genotype , Drug Interactions , Cytochrome P-450 Enzyme SystemABSTRACT
BACKGROUND: In recent years, the placement of a subacromial balloon (SAB) spacer has emerged as a treatment option for massive irreparable rotator cuff tears (MIRCTs); however, there is significant controversy regarding its utility in comparison with other surgical interventions. PURPOSE: To compare outcomes after SAB spacer placement versus arthroscopic debridement for MIRCTs. STUDY DESIGN: Dual-armed systematic review and meta-analysis (level IV evidence). METHODS: A literature search of PubMed (MEDLINE), Scopus, and CINAHL Complete databases for articles published before May 7, 2022, was conducted to identify patients with MIRCTs undergoing the 2 procedures. For the SAB arm, 14 of 449 studies were considered eligible for inclusion, while 14 of 272 studies were considered eligible for inclusion in the debridement arm. RESULTS: In total, 528 patients were eligible for inclusion in the SAB arm and 479 patients in the debridement arm, and 69.9% of patients undergoing SAB placement also underwent concomitant debridement. Decreases in the visual analog scale (VAS) pain score and increases in the Constant score were found to be significantly larger after debridement (-0.7 points [P < .001] and +5.5 points [P < .001], respectively), although the Patient Acceptable Symptom State for the VAS was not achieved after either procedure. Both SAB placement and debridement significantly improved range of motion in forward flexion/forward elevation, internal and external rotation, and abduction (P < .001). Rates of general complication were higher after debridement versus SAB placement (5.2% ± 5.6% vs 3.5% ± 6.3%, respectively; P < .001); however, there were no significant differences between SAB placement and debridement in rates of persistent symptoms requiring a reintervention (3.3% ± 6.2% vs 3.8% ± 7.3%, respectively; P = .252) or reoperation rates (5.1% ± 7.6% vs 4.8% ± 8.4%, respectively; P = .552). The mean time to conversion to reverse total shoulder arthroplasty was 11.0 versus 25.4 months, respectively, for the SAB versus debridement arm. CONCLUSION: While SAB placement was associated with acceptable postoperative outcomes in the treatment of MIRCTs, there was no clear benefit over debridement alone. Shorter operative times coupled with better postoperative outcomes and longer times to conversion to reverse total shoulder arthroplasty rendered debridement a more attractive option. While there may be a role for SAB placement in poor surgical candidates, there is burgeoning evidence to support debridement alone without SAB placement for the treatment of MIRCTs.
Subject(s)
Rotator Cuff Injuries , Humans , Rotator Cuff Injuries/surgery , Debridement , Treatment Outcome , Arm/surgery , Arthroplasty , Arthroscopy/methods , Range of Motion, ArticularABSTRACT
Current strategies to understand the molecular basis of Marek's disease virus (MDV) virulence primarily consist of cataloguing divergent nucleotides between strains with different phenotypes. However, each MDV strain is typically represented by a single consensus genome despite the confirmed existence of mixed viral populations. To assess the reliability of single-consensus interstrain genomic comparisons, we obtained two additional consensus genomes of vaccine strain CVI988 (Rispens) and two additional consensus genomes of the very virulent strain Md5 by sequencing viral stocks and cultured field isolates. In conjunction with the published genomes of CVI988 and Md5, this allowed us to perform 3-way comparisons between consensus genomes of the same strain. We found that consensus genomes of CVI988 can vary in as many as 236 positions involving 13 open reading frames (ORFs). In contrast, we found that Md5 genomes varied only in 11 positions involving a single ORF. Phylogenomic analyses showed all three Md5 consensus genomes clustered closely together, while also showing that CVI988 GenBank.BAC diverged from CVI988 Pirbright.lab and CVI988 USDA.PA.field . Comparison of CVI988 consensus genomes revealed 19 SNPs in the unique regions of CVI988 GenBank.BAC that were not present in either CVI988 Pirbright.lab or CVI988 USDA.PA.field . Finally, we evaluated the genomic heterogeneity of CVI988 and Md5 populations by identifying positions with >2% read support for alternative alleles in two ultra-deeply sequenced samples. We were able to confirm that both populations of CVI988 and Md5 were mixed, exhibiting a total of 29 and 27 high-confidence minor variant positions, respectively. We did not find any evidence of minor variants in the positions corresponding to the 19 SNPs in the unique regions of CVI988 GenBank.BAC . Taken together, our findings confirm that consensus genomes of the same strain of MDV can vary and suggest that multiple consensus genomes per strain are needed in order to maximize the accuracy of interstrain genomic comparisons.