Innovation in Orthopaedics: Part 2-How to Translate Ideas and Research into Clinical Practice.

PURPOSE OF REVIEW: This paper presents some approaches and techniques for translating an idea or research into clinical practice, considering the innovation development process. RECENT FINDINGS: Innovative tools have been a key solution for healthcare problems, such as musculoskeletal disorders, which represent a great economic burden and are among the leading causes of disability. There has been an increase in publications on this topic, but there has been no analysis of the process of innovation development. This review describes the innovation phases for translating an idea or research into clinical practice, considering the stages of discovering the opportunity, innovation creation, project specification, technology development, and innovation launch. An analysis of the innovation development process to translate an idea or research into clinical practice, including concepts, approaches, and techniques that shows the "why", "how", and "what" of innovation.

Disparities of COVID-19 and HIV Occurrence Based on Neighborhood Infection Incidence in Philadelphia, Pennsylvania.

Objectives. To evaluate the occurrence of HIV and COVID-19 infections in Philadelphia, Pennsylvania, through July 2020 and identify ecological correlates driving racial disparities in infection incidence. Methods. For each zip code tabulation area, we created citywide comparison Z-score measures of COVID-19 cases, new cases of HIV, and the difference between the scores. Choropleth maps were used to identify areas that were similar or dissimilar in terms of disease patterning, and weighted linear regression models helped identify independent ecological predictors of these patterns. Results. Relative to COVID-19, HIV represented a greater burden in Center City Philadelphia, whereas COVID-19 was more apparent in Northeast Philadelphia. Areas with a greater proportion of Black or African American residents were overrepresented in terms of both diseases. Conclusions. Although race is a shared nominal upstream factor that conveys increased risk for both infections, an understanding of separate structural, demographic, and economic risk factors that drive the overrepresentation of COVID-19 cases in racial/ethnic communities across Philadelphia is critical. Public Health Implications. Difference-based measures are useful in identifying areas that are underrepresented or overrepresented with respect to disease occurrence and may be able to elucidate effective or ineffective mitigation strategies. (Am J Public Health. 2022;112(3):408-416. https://doi.org/10.2105/AJPH.2021.306538).

Four Decades of Epidemiologic Science on HIV Infection and Disease, and Its Impact on Public Health Practice and Policy for Sexual and Gender Minority Persons.

Even at the cusp of the second decade of the new millennia, HIV continues to be a significant public health challenge for sexual and gender minorities (SGM). Men who have sex with men and transgender women, in particular, continue to report higher rates of HIV incidence compared to their heterosexual counterparts, while facing significant barriers to comprehensive sexual healthcare. In Delaware, HIV infection impacts a substantial number of individuals with approximately 14.5 incident cases per 100,000. This ranks Delaware as the 14th highest for HIV incidence among U.S. states. However, the largest healthcare provider in Delaware, Christiana Care Health System, has created many health initiatives to support the health needs of SGM and those living with HIV. The current sustained rate of HIV infection indicates the need for enhanced epidemiologic work to identify HIV cases in subgroups of diverse sexuality and gender identity, collaboration within and across research institution and community organizations, as well as engagement in creative solutions that target the multiple levels of factors contributing to HIV incidence. In addition, it is imperative that local agencies and health organizations continue to support these communities of SGM individuals during the current sociopolitical climate of the national U.S. government.

Percutaneous computed tomography-guided biopsy performed by thoracic surgeons in 955 patients: A paradigm shift in image-guided thoracic procedures.

OBJECTIVES: Computed tomography-guided fine needle aspiration (CT-FNA) biopsy is a well-established diagnostic technique in the evaluation of lung nodules that is performed by radiologists in most centers. In this series, we analyzed the diagnostic and perioperative outcomes following CT-FNA performed by a dedicated group of thoracic surgeons. METHODS: We conducted a retrospective analysis of 955 patients undergoing CT-FNA by the thoracic surgery service. Primary outcome variables included diagnostic yield and accuracy, number of needle passes, complication rates, and adequacy of specimen for molecular testing. RESULTS: A satisfactory diagnostic specimen was obtained in 94.1% of cases. The average number of needle passes was 3.2 ± 1.5 (range, 1-10 passes). Diagnostic yield was significantly improved by increasing the number of passes from 1 to 2 to 3 passes (P = .0003). CT-FNA diagnostic accuracy was 88.8%. Diagnostic accuracy did not significantly improve with ≥4 passes (P = .20). Molecular testing was successful in 43.1%, and did not improve with ≥4 passes (P = .5). Molecular testing success did improve with the addition of core needle biopsy (P = .005). The pneumothorax rate for CT-FNA alone was 26.4%, and increased with ≥4 passes (P = .009). The median length of stay for CT-FNA alone was 0 days (range, 0-74 days), with same-day discharge in 67.5% of patients. CONCLUSIONS: Thoracic surgeons can perform CT-FNA with excellent diagnostic yield and accuracy. Diagnostic yield, accuracy, and success in molecular testing do not improve with ≥4 CT-FNA passes. Pneumothorax rates do increase with ≥4 passes. The addition of core needle biopsy enhances success with molecular testing.

Cost-Effectiveness Analysis of a Military Hearing Conservation Program.

INTRODUCTION: Occupational noise threatens U.S. worker health and safety and commands a significant financial burden on state and federal government worker compensation programs. Previous studies suggest that hearing conservation programs have contributed to reduced occupational hearing loss for noise-exposed workers. Many military personnel are overexposed to noise and are provided hearing conservation services. Select military branches require all active duty personnel to follow hearing conservation program guidelines, regardless of individual noise exposure. We evaluated the cost-effectiveness of a military hearing conservation program, relative to no intervention, in relation to cases of hearing loss prevented. METHODS: We employed cost-effectiveness analytic methods to compare the costs and effectiveness, in terms of hearing loss cases prevented, of a military hearing conservation program relative to no program. We used costs and probability estimates available in the literature and publicly available sources. The effectiveness of the interventions was analyzed based on whether hearing loss occurred over a 20-yr time frame. RESULTS: The incremental cost-effectiveness ratio of the hearing conservation program compared with no intervention was $10,657 per case of hearing loss prevented. Workers were 28% less likely to sustain hearing loss in our model when they received the hearing conservation program compared with no intervention, which reflected the greater effectiveness of the hearing conservation program. Cost-effectiveness results were sensitive to estimated values for the probability of acquiring hearing loss from both interventions and the cost of hearing protection. We performed a Monte Carlo probabilistic sensitivity analysis where we simultaneously varied all the model parameters to their extreme plausible bounds. When we ran 10,000 Monte Carlo iterations, we observed that the hearing conservation program was more cost-effective in 99% of cases when decision makers were willing to pay $64,172 per case of hearing loss prevented. CONCLUSIONS: Conceding a lifetime cost for service-related compensation for hearing loss per individual of $64,172, the Department of Defense Hearing Conservation Program is an economically reasonable program relative to no intervention, if a case of hearing loss avoided costs $10,657. Considering the net difference of the costs and comparative benefits of both treatment strategies, providing a hearing conservation program for all active duty military workers may be a cost-effective intervention for the Department of Defense.

The Effect of PrEP on HIV Incidence Among Men Who Have Sex With Men in the Context of Condom Use, Treatment as Prevention, and Seroadaptive Practices.

BACKGROUND: HIV preexposure prophylaxis (PrEP) is an effective tool in preventing HIV infection among high-risk men who have sex with men (MSM). It is unknown how effective PrEP is in the context of other implemented HIV prevention strategies, including condom use, seroadaption, and treatment as prevention (TasP). We evaluate the impact of increasing uptake of PrEP in conjunction with established prevention strategies on HIV incidence in a high-risk population of MSM through simulation. METHODS: Agent-based simulation models representing the sexual behavior of high-risk, urban MSM in the United States over the period of 1 year were used to evaluate the effect of PrEP on HIV infection rates. Simulations included data for 10,000 MSM and compared increasing rates of PrEP uptake under 8 prevention paradigms: no additional strategies, TasP, condom use, seroadaptive behavior, and combinations thereof. RESULTS: We observed a mean of 103.2 infections per 10,000 MSM in the absence of any prevention method. PrEP uptake at 25% without any additional prevention strategies prevented 30.7% of infections. In the absence of PrEP, TasP, condom use, and seroadaptive behavior independently prevented 27.1%, 48.8%, and 37.7% of infections, respectively, and together prevented 72.2%. The addition of PrEP to the 3 aforementioned prevention methods, at 25% uptake, prevented an additional 5.0% of infections. CONCLUSIONS: To achieve a 25% reduction in HIV infections by 2020, HIV prevention efforts should focus on significantly scaling up access to PrEP in addition to HIV testing, access to antiretroviral therapy, and promoting condom use.

Bayesian Approaches to Racial Disparities in HIV Risk Estimation Among Men Who Have Sex with Men.

BACKGROUND: Men who have sex with men (MSM) continue to be overrepresented for new HIV infections compared with non-MSM. This disparity becomes even more alarming when considering racial groups. We describe the race-specific effects in HIV prevalence among MSM relative to non-MSM and explore the causes of disagreement among estimates. METHODS: We used data from the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative longitudinal survey conducted in the US Bayesian learning corrected for potential misclassification of MSM status and adjusted for residual confounding, hypothesized to explain the MSM racial disparity in HIV. We articulated the structure and strength of the latent confounders that would make race-specific risk gradients equivalent. RESULTS: Compared with non-MSM, the adjusted prevalence odds ratio (POR) and 95% credible interval for black MSM having self-reported HIV infection was 5.8 (2.0, 16), while the POR for white MSM was 12 (4.2, 31). For all MSM, the POR for HIV infection was 9.3 (3.6, 23) with black men having 2.6 times the odds of prevalent infection compared with white men. CONCLUSIONS: The observed race-specific associations in MSM are likely not due to misclassification alone, but represent a constellation of factors that differ between racial groups. We recommend specific risk factors in surveys needed to further identify the behavioral characteristics that lead to the observed differences when the estimates are stratified by race.

Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients.

UNLABELLED: Calcineurin inhibitor-associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. METHODS: This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m(2) or greater improvement in estimated glomerular filtration rate from randomization to month 24. RESULTS: The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m(2) or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). CONCLUSIONS: Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus.

To Be or Not to Be: Bayesian Correction for Misclassification of Self-reported Sexual Behaviors Among Men Who Have Sex with Men.

BACKGROUND: Inferring sexual behavior of a stigmatized minority through self-reported sexual identity is subject to misclassification and can lead to biased results. We quantify the degree of this misclassification and perform a Bayesian correction of the risk of HIV infection in relation to self-reported sexual behavior. METHODS: Sensitivity and specificity of self-reported men who have sex with men in ascertaining sexual behavior was derived from validation data, as was the informative prior on the association of same-sex behavior with self-reported HIV infection. Using these priors, we performed two separate Bayesian analyses of National Epidemiologic Survey on Alcohol and Related Conditions data for the odds of self-reported HIV positivity, adjusting for differential misclassification of self-reported same-sex behavior indicated by either partner gender or sexual identity. RESULTS: We found differential exposure misclassification with specificity exceeding sensitivity, and higher misclassification rates based on sexual identity compared with partner gender. Sexual identity and partner gender displayed different associations with HIV infection in the raw data but these became virtually identical when adjusted for estimates of misclassification of sexual behavior by these two indicators. The estimate of prevalence of same-sex behavior associated with an elevated risk of HIV infection decreased after adjustment for misclassification. CONCLUSIONS: Studies of risk due to same-sex behavior are likely biased when they rely on self-identification for ascertainment of risk factors, especially when self-reported identity is used. The implications of our findings on risk modeling cannot be assumed to be trivial due to substantial shifts in distributions of risk and prevalence of exposure.

Congenital chloride-losing diarrhea in a Mexican child with the novel homozygous SLC26A3 mutation G393W.

Congenital chloride diarrhea is an autosomal recessive disease caused by mutations in the intestinal lumenal membrane Cl(-)/HCO(-) 3 exchanger, SLC26A3. We report here the novel SLC26A3 mutation G393W in a Mexican child, the first such report in a patient from Central America. SLC26A3 G393W expression in Xenopus oocytes exhibits a mild hypomorphic phenotype, with normal surface expression and moderately reduced anion transport function. However, expression of HA-SLC26A3 in HEK-293 cells reveals intracellular retention and greatly decreased steady-state levels of the mutant polypeptide, in contrast to peripheral membrane expression of the wildtype protein. Whereas wildtype HA-SLC26A3 is apically localized in polarized monolayers of filter-grown MDCK cells and Caco2 cells, mutant HA-SLC26A3 G393W exhibits decreased total polypeptide abundance, with reduced or absent surface expression and sparse punctate (or absent) intracellular distribution. The WT protein is similarly localized in LLC-PK1 cells, but the mutant fails to accumulate to detectable levels. We conclude that the chloride-losing diarrhea phenotype associated with homozygous expression of SLC26A3 G393W likely reflects lack of apical surface expression in enterocytes, secondary to combined abnormalities in polypeptide trafficking and stability. Future progress in development of general or target-specific folding chaperonins and correctors may hold promise for pharmacological rescue of this and similar genetic defects in membrane protein targeting.

A study of adult T-cell leukemia/lymphoma incidence in central Brooklyn

Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in-patient beds in the catchment area, approximately 83 percent were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted.(Au)