Symptomatic aseptic loosening of a short humeral stem following anatomic total shoulder arthroplasty.

INTRODUCTION: The rate of aseptic humeral component loosening with standard-length stems is historically so low (0.3%) that presence of humeral loosening was given substantial weight in defining periprosthetic shoulder infection by the International Consensus Meeting (ICM) in 2018. This study aims to confirm that the historically low rate of humeral stem aseptic loosening is not affected by the adoption of a novel short humeral stem. METHODS: Following institutional review board approval, this retrospective multi-institutional study was undertaken. A review of anatomic total shoulder arthroplasty (TSA) cases at 3 institutions provided 184 shoulders that received TSA with a grit-blasted, rectangular short humeral stem without ingrowth coating (Univers Apex; Arthrex). The average patient age was 62.1 years (range: 30-84), and 57.1% (105/184) were male. One-year radiographic follow-up was achieved in 64.7%. Patient clinical charts were reviewed for onset of newly painful shoulders, radiographic evidence of loosening, and return to the operating room for any reason. All patients with concern for clinically significant humeral loosening underwent workup for periprosthetic shoulder infection. Immediate postoperative films were reviewed to identify any differences in prosthetic canal fit. The definition of periprosthetic shoulder infection used was provided by the recent ICM shoulder guidelines. RESULTS: Twenty-three (12.5%) patients presented with a painful shoulder and radiographic concern for potential humeral loosening at a mean follow-up of 1.5 years (range: 1.5 months-3.4 years). Thirteen (7.1%) of these underwent revision shoulder arthroplasty where a loose stem was confirmed. All revisions underwent tissue culture, and 3 cases were consistent with probable or possible periprosthetic infection at the time of revision arthroplasty. The rate of symptomatic aseptic humeral loosening in this series was 10.9% (20/184), with 5.4% undergoing revision surgery. Patients with symptomatic aseptic humeral loosening were more likely to be male (90.5%) than those patients without symptoms (52.8%, P < .001). There were no differences in canal fit between patients with concern for symptomatic loosening and those with pain-free, stable implants. CONCLUSION: In this multisurgeon, multicenter study, the early humeral loosening rate for this stem design far outpaces previously reported rates, and this study likely under-reports the true incidence of clinically significant loosening as it only contains limited short-term follow-up. The perception that humeral loosening is nearly pathognomonic for periprosthetic shoulder infection should be reconsidered for certain short humeral stem designs.

Trends in open shoulder surgery among early career orthopedic surgeons: who is doing what?

BACKGROUND: The incidence of various open shoulder procedures has changed over time. In addition, various fellowships provide overlapping training in open shoulder surgery. There is a lack of information regarding the relationship between surgeon training and open shoulder procedure type and incidence in early career orthopedic surgeons. METHODS: The American Board of Orthopaedic Surgery Part-II database was queried from 2002 to 2016 for reported open shoulder procedures. The procedures were categorized as follows: arthroplasty, revision arthroplasty, open instability, trauma, and open rotator cuff. We evaluated procedure trends as well as their relationship to surgeon fellowship categorized by Sports, Shoulder/Elbow, Hand, Trauma, and "Other" fellowship as well as no fellowship training. We additionally evaluated complication data as it related to procedure, fellowship category, and volume. RESULTS: Over the 2002-2016 study period, there were increasing cases of arthroplasty, revision arthroplasty, and trauma (P < .001). There were decreasing cases in open instability and open rotator cuff (P < .001). Those with Sports training reported the largest overall share of open shoulder cases. Those with Shoulder/Elbow training reported an increasing overall share of arthroplasty cases and higher per candidate case numbers. The percentage of early career orthopedic surgeons reporting 5 or more arthroplasty cases was highest among Shoulder/Elbow candidates (P < .001). Across all procedures, those without fellowship training were least likely to report a complication (odds ratio [OR], 0.76; 95% confidence interval, 0.67-0.86; P < .001). Shoulder/Elbow candidates were least likely to report an arthroplasty complication (OR, 0.84, P = .03) as was any surgeon reporting 5 or more arthroplasty cases (OR, 0.81; 95% confidence interval, 0.70-0.94; P = .006). CONCLUSION: The type and incidence of open shoulder surgery procedures continues to change. Among early career surgeons, those with more specific shoulder training are now performing the majority of arthroplasty-related procedures, and early career volume inversely correlates with complications.

Tobacco industry response to a ban on lights descriptors on cigarette packaging and population outcomes.

OBJECTIVE: The WHO Framework Convention on Tobacco Control and its Guidelines recommend nations ban the use of misleading terms, such as 'light' and 'mild' on tobacco product advertising, packaging and labelling. Many nations, including the USA, have implemented such bans and some have introduced or passed legislation requiring plain packaging on tobacco products. We previously reported that manufacturers in the USA responded by replacing lights terms with colour terms and related colour-coding of packages. This study examines population outcomes and public health impact of the US ban. METHODS: We examined available data regarding a) per cent filter ventilation strata used to designate lights subbrand categories; b) market share per tar yield; c) initiation and use of cigarettes by lights categories and d) overall cigarette consumption to identify changes from before to after the ban. We used interrupted time series multivariable logistic regression and joinpoint regression models to test for changes in rates and temporal trends associated with the ban. RESULTS: The per cent filter ventilation strata used to designate lights subbrand categories were maintained in the colour named subbrands. No change was observed following the ban in lights market share, relative prevalence of lights versus non-lights smoking or relative smoking initiation on lights versus non-lights among all ages or among youth in particular. The rate of decline in per capita cigarette consumption slowed by 37% from the period 2007-2010 to 2010-2014. CONCLUSIONS: This study strongly suggests that manufacturers' circumvention prevented the lights descriptor ban from succeeding as intended, most likely perpetuating the misleading consumer perceptions about relative risks, while failing to increase smoking cessation and reduce initiation. Laws requiring generic (plain) and elimination of subbrand descriptors should prevent evasion of legislation banning the use of specific terms through marketing, regulatory and legal challenges.

Public Awareness of and Contact With Physicians Who Receive Industry Payments: A National Survey.

BACKGROUND: The Physician Payments Sunshine Act, part of the Affordable Care Act, requires pharmaceutical and medical device firms to report payments they make to physicians and, through its Open Payments program, makes this information publicly available. OBJECTIVE: To establish estimates of the exposure of the American patient population to physicians who accept industry payments, to compare these population-based estimates to physician-based estimates of industry contact, and to investigate Americans' awareness of industry payments. DESIGN: Cross-sectional survey conducted in late September and early October 2014, with data linkage of respondents' physicians to Open Payments data. PARTICIPANTS: A total of 3542 adults drawn from a large, nationally representative household panel. MAIN MEASURES: Respondents' contact with physicians reported in Open Payments to have received industry payments; respondents' awareness that physicians receive payments from industry and that payment information is publicly available; respondents' knowledge of whether their own physician received industry payments. KEY RESULTS: Among the 1987 respondents who could be matched to a specific physician, 65% saw a physician who had received an industry payment during the previous 12 months. This population-based estimate of exposure to industry contact is much higher than physician-based estimates from the same period, which indicate that 41% of physicians received an industry payment. Across the six most frequently visited specialties, patient contact with physicians who had received an industry payment ranged from 60 to 85%; the percentage of physicians with industry contact in these specialties was much lower (35-56%). Only 12% of survey respondents knew that payment information was publicly available, and only 5% knew whether their own doctor had received payments. CONCLUSIONS: Patients' contact with physicians who receive industry payments is more prevalent than physician-based measures of industry contact would suggest. Very few Americans know whether their own doctor has received industry payments or are aware that payment information is publicly available.

Substantial Equivalence Standards in Tobacco Governance: Statutory Clarity and Regulatory Precedent for the FSPTCA.

The Family Smoking Prevention and Tobacco Control Act (FSPTCA) of 2009 creates the first national system of premarket regulation of tobacco products in American history. The FDA must now review and give marketing authorization to all new tobacco products, based on a public health standard, before they can be legally marketed. Yet the law also contains an alternative pathway for market entry-the substantial equivalence (SE) clause-by which novel and altered tobacco products can be marketed by demonstrating their substantial equivalence to existing products. Over 99 percent of tobacco product applications sent to the FDA under the new law have used this mechanism, and loose application of the SE mechanism carries the risk of undoing the FDA's gatekeeping power under the law. We review the statutory and regulatory precedent for SE, examining the FSPTCA itself as well as regulatory precedent from drug and device regulation (from which the term substantial equivalence and much of the associated statutory language was derived). Our review of standards and scientific precedent demonstrates that exacting scrutiny under the public health standard should govern all SE reviews and that clinical data incorporating social scientific evidence should be routinely required for SE claims by tobacco product sponsors.

Global health security: the wider lessons from the west African Ebola virus disease epidemic.

The Ebola virus disease outbreak in West Africa was unprecedented in both its scale and impact. Out of this human calamity has come renewed attention to global health security--its definition, meaning, and the practical implications for programmes and policy. For example, how does a government begin to strengthen its core public health capacities, as demanded by the International Health Regulations? What counts as a global health security concern? In the context of the governance of global health, including WHO reform, it will be important to distil lessons learned from the Ebola outbreak. The Lancet invited a group of respected global health practitioners to reflect on these lessons, to explore the idea of global health security, and to offer suggestions for next steps. Their contributions describe some of the major threats to individual and collective human health, as well as the values and recommendations that should be considered to counteract such threats in the future. Many different perspectives are proposed. Their common goal is a more sustainable and resilient society for human health and wellbeing.

Novel Antibiotic-loaded Point-of-care Implant Coating Inhibits Biofilm.

BACKGROUND: Orthopaedic biomaterials are susceptible to biofilm formation. A novel lipid-based material has been developed that may be loaded with antibiotics and applied as an implant coating at point of care. However, this material has not been evaluated for antibiotic elution, biofilm inhibition, or in vivo efficacy. QUESTIONS/PURPOSES: (1) Do antibiotic-loaded coatings inhibit biofilm formation? (2) Is the coating effective in preventing biofilm in vivo? METHODS: Purified phosphatidylcholine was mixed with 25% amikacin or vancomycin or a combination of 12.5% of both. A 7-day elution study for coated titanium and stainless steel coupons was followed by turbidity and zone of inhibition assays against Staphylococcus aureus and Pseudomonas aeruginosa. Coupons were inoculated with bacteria and incubated 24 hours (N = 4 for each test group). Microscopic images of biofilm were obtained. After washing and vortexing, attached bacteria were counted. A mouse biofilm model was modified to include coated and uncoated stainless steel wires inserted into the lumens of catheters inoculated with a mixture of S aureus or P aeruginosa. Colony-forming unit counts (N = 10) and scanning electron microscopy imaging of implants were used to determine antimicrobial activity. RESULTS: Active antibiotics with colony inhibition effects were eluted for up to 6 days. Antibiotic-loaded coatings inhibited biofilm formation on in vitro coupons (log-fold reductions of 4.3 ± 0.4 in S aureus and 3.1 ± 0 for P aeruginosa in phosphatidylcholine-only coatings, 5.6 ± 0 for S aureus and 3.1 ± 0 for P aeruginosa for combination-loaded coatings, 5.5 ± 0.3 for S aureus in vancomycin-loaded coatings, and 3.1 ± 0 for P aeruginosa for amikacin-loaded coatings (p < 0.001 for all comparisons of antibiotic-loaded coatings against uncoated controls for both bacterial strains, p < 0.001 for comparison of antibiotic-loaded coatings against phosphatidylcholine only for S aureus, p = 0.54 for comparison of vancomycin versus combination coating in S aureus, P = 0.99 for comparison of antibiotic- and unloaded phosphatidylcholine coatings in P aeruginosa). Similarly, antibiotic-loaded coatings reduced attachment of bacteria to wires in vivo (log-fold reduction of 2.54 ± 0; p < 0.001 for S aureus and 0.83 ± 0.3; p = 0.112 for P aeruginosa). CONCLUSIONS: Coatings deliver active antibiotics locally to inhibit biofilm formation and bacterial growth in vivo. Future evaluations will include orthopaedic preclinical models to confirm therapeutic efficacy. CLINICAL RELEVANCE: Clinical applications of local drug delivery coating could reduce the rate of implant-associated infections.

Leah Z. Rand, Daniel P. Carpenter, Aaron S. Kesselheim, Anushka Bhaskar, Jonathan J. Darrow, and William B. Feldman Reply.

The authors respond to a letter by Mitchell Berger in the March-April 2024 issue of the Hastings Center Report concerning their essay "Securing the Trustworthiness of the FDA to Build Public Trust in Vaccines."

Trust in the Food and Drug Administration: A National Survey Study.

Building trust in public health agencies like the US Food and Drug Administration (FDA) has become a key government priority. Understanding the roots of FDA mistrust is important if the agency is to develop targeted messaging and reforms aimed at building confidence in the agency. We conducted a survey of 2,021 respondents in the US probing attitudes toward the FDA. The primary outcome was FDA trust, defined as the mean score that each respondent assigned to the FDA across four prespecified axes: (1) competence and effectiveness; (2) commitment to acting in the best interests of the American public; (3) abiding by the rules and regulations set forth by policy or law; and (4) expertise in health, science, and medicine. On multivariable ordinal logistic regression, FDA mistrust was associated with female gender (odds ratio [OR] = 0.74, 95% confidence interval [CI] 0.62-0.88), rural community (OR 0.85, 95% CI 0.75-0.96), conservative political views (OR 0.77, 95% CI 0.74-0.81), worse self-reported health (OR 0.89, 95% CI 0.80-0.98), lower satisfaction with health care received (OR 0.63, 95% CI 0.56-0.71), less attention to health and science news (OR 0.72, 95% CI 0.64-0.80), and not having children under the age of 18 (OR 0.72, 95% CI 0.60-0.86). These findings underscore the challenges faced by US political leaders in convincing a heterogeneous American public to trust the FDA. The FDA should develop and deploy targeted outreach strategies to populations with lower levels of trust and strengthen internal processes that minimize biases and ensure sound decision-making.

What Should Be Clinicians' Roles in Regulatory Assessment of Prospective Interventions' Risks of Exacerbating Inequity?

When there is an evidence base that could be used credibly to justify expedited US Food and Drug Administration review, emergency use authorization, or approval, interventions-in-development must be evaluated in terms of their possible downstream influence on public trust and confidence in regulatory processes during a national public health crisis. When regulatory decisions express overconfidence about a prospective intervention's success, there is risk that the costliness of or misinformation about the intervention will exacerbate health inequity. A converse risk is regulators' underestimation of an intervention's value in treating populations at risk for inequitable care. This article considers the nature and scope of clinicians' roles in regulatory processes in which such risks must be considered and balanced to promote public safety and public health.

The Revolving Door In Health Care Regulation.

Of people appointed to the Department of Health and Human Services between 2004 and 2020, 15 percent had been employed in private industry immediately before their appointment. At the end of their tenure, 32 percent exited to industry. The greatest net exits to industry were from the Centers for Disease Control and Prevention and the Centers for Medicare and Medicaid Services.

Securing the Trustworthiness of the FDA to Build Public Trust in Vaccines.

The Covid-19 pandemic highlighted the need to examine public trust in the U.S. Food and Drug Administration (FDA) vaccine approval process and the role of political influence in the FDA's decisions. Ensuring that the FDA is itself trustworthy is important for justifying public trust in its actions, like vaccine approvals, thereby promoting public health. We propose five conditions of trustworthiness that the FDA should meet when it reviews vaccines, even during emergencies: consistency with rules, proper expert or political decision-makers, proper decision-making and noninterference, connection to public preference, and transparency of both reasons and procedures. The five conditions provide a road map of procedural and substantive requirements, which the FDA has variably implemented, focused on ensuring appropriate influence of political interests. While being a trustworthy agency cannot guarantee the public's trust, implementing these conditions builds a groundwork for public trust.

Warnings without guidance: patient responses to an FDA warning about ezetimibe.

BACKGROUND: In January 2008, the Food and Drug Administration (FDA) communicated concerns about the efficacy of ezetimibe, but did not provide clear clinical guidance, and substantial media attention ensued. We investigated the proportion of patients who discontinued therapy and switched to a clinically appropriate alternative after the FDA communication. METHODS: Using claims data from a national pharmacy benefits manager, we created a rolling cohort of new users of ezetimibe between January 2006 and August 2008 and created a supply diary for each patient in the year after cohort entry. A patient was identified as nonpersistent if a gap of 90 days was seen in the diary. Using segmented linear regression, we compared rates of nonpersistence before and after the FDA communication and assessed patient-level characteristics associated with discontinuation. Among nonpersistent patients, we determined whether a patient made a clinically appropriate switch in the subsequent 90 days by adding a new cholesterol-lowering medication or by increasing the dose of an existing one. We used a weighted t test to compare the rates of appropriate switching before and after the communication. RESULTS: Among 867,027 new ezetimibe users, 407,006 (46.9%) were nonpersistent in the first year. After the FDA communication, the monthly level of ezetimibe nonpersistence increased by 5.7 percentage points (P<0.0001). Younger patients, those who lived in low-income zip codes, and female patients were less likely to discontinue therapy (P<0.0001 for all). Among nonpersistent patients, rates of clinically appropriate switching increased from 10.8% before to 16.5% after the FDA warning (P = 0.004). CONCLUSIONS: A substantial increase in ezetimibe nonpersistence rates was seen after an FDA communication regarding its efficacy and following associated media attention, and a small proportion of patients made a clinically appropriate switch after discontinuation. Further consideration is needed to deliver messages that promote appropriate use of chronic therapy rather than simply reduce use.

Land use and soil characteristics affect soil organisms differently from above-ground assemblages.

BACKGROUND: Land-use is a major driver of changes in biodiversity worldwide, but studies have overwhelmingly focused on above-ground taxa: the effects on soil biodiversity are less well known, despite the importance of soil organisms in ecosystem functioning. We modelled data from a global biodiversity database to compare how the abundance of soil-dwelling and above-ground organisms responded to land use and soil properties. RESULTS: We found that land use affects overall abundance differently in soil and above-ground assemblages. The abundance of soil organisms was markedly lower in cropland and plantation habitats than in primary vegetation and pasture. Soil properties influenced the abundance of soil biota in ways that differed among land uses, suggesting they shape both abundance and its response to land use. CONCLUSIONS: Our results caution against assuming models or indicators derived from above-ground data can apply to soil assemblages and highlight the potential value of incorporating soil properties into biodiversity models.

Drug-review deadlines and safety problems.

BACKGROUND: The Prescription Drug User Fee Act (PDUFA) imposes deadlines for the completion of drug reviews by the Food and Drug Administration (FDA). Critics have suggested that these deadlines may result in rushed approvals and the emergence of unanticipated safety problems once a product is in clinical use. METHODS: We assessed the association between the PDUFA deadlines and the timing of FDA drug approval by constructing dynamic Cox proportional-hazards models of review times for all new molecular entities approved between 1950 and 2005. To determine whether the deadlines were associated with postmarketing safety problems, we focused on drugs submitted since January 1993, when the deadlines were first imposed. We used exact logistic regression to determine whether drugs approved immediately before the deadlines were associated with a higher rate of postmarketing safety problems (e.g., withdrawals and black-box warnings) than drugs approved at other times. RESULTS: Initiation of the PDUFA requirements concentrated the number of approval decisions made in the weeks immediately preceding the deadlines. As compared with drugs approved at other times, drugs approved in the 2 months before their PDUFA deadlines were more likely to be withdrawn for safety reasons (odds ratio, 5.5; 95% confidence interval [CI], 1.3 to 27.8), more likely to carry a subsequent black-box warning (odds ratio, 4.4; 95% CI, 1.2 to 20.5), and more likely to have one or more dosage forms voluntarily discontinued by the manufacturer (odds ratio, 3.3; 95% CI, 1.5 to 7.5). CONCLUSIONS: PDUFA deadlines have appreciably changed the approval decisions of the FDA. Once medications are in clinical use, the discovery of safety problems is more likely for drugs approved immediately before a deadline than for those approved at other times.

US pharmaceutical innovation in an international context.

OBJECTIVES: We explored whether the United States, which does not regulate pharmaceutical prices, is responsible for the development of a disproportionate share of the new molecular entities (NMEs; a drug that does not contain an active moiety previously approved by the Food and Drug Administration) produced worldwide. METHODS: We collected data on NMEs approved between 1992 and 2004 and assigned each NME to an inventor country. We examined the relation between the proportion of total NMEs developed in each country and the proportion of total prescription drug spending and gross domestic product (GDP) of each country represented. RESULTS: The United States accounted for 42% of prescription drug spending and 40% of the total GDP among innovator countries and was responsible for the development of 43.7% of the NMEs. The United Kingdom, Switzerland, and a few other countries innovated proportionally more than their contribution to GDP or prescription drug spending, whereas Japan, South Korea, and a few other countries innovated less. CONCLUSIONS: Higher prescription drug spending in the United States does not disproportionately privilege domestic innovation, and many countries with drug price regulation were significant contributors to pharmaceutical innovation.

Clinical Outcomes and Cadaveric Biomechanical Analysis of Endoscopic Percutaneous Achilles Tendon Rupture Repair With Absorbable Suture.

BACKGROUND: Percutaneous repair of acute Achilles tendon rupture (ATR) continues to gain in popularity. The primary aim of the study was to review the outcomes of a patient cohort undergoing a novel technique of endoscopic percutaneous Achilles tendon repair with absorbable suture. A secondary purpose of this study was to evaluate the basic biomechanical properties of the technique. METHODS: A cohort of 30 patients who underwent percutaneous ATR repair was retrospectively analyzed with Achilles Tendon Rupture Scores (ATRS), complications, and additional outcome measures. For a biomechanical analysis portion of the study, 12 cadaveric specimens were paired and randomized to either novel percutaneous repair or open Kessler repair with absorbable suture. These specimens were subjected to 2 phases of cyclical testing (100 cycles 10-43 N followed by 200 cycles 10-86 N) and ultimate strength testing. RESULTS: In the clinical portion of the study we report excellent patient reported outcomes (mean ATRS 94.1), high level of return to sport, and high patient satisfaction. One partial re-rupture was reported but with no major wound or neurologic complications. In the biomechanical portion of the study we found no significant difference in tendon gapping between percutaneous and open repairs in phase 1 of testing. In phase 2, increased gapping occurred between percutaneous (17.8 mm [range 10.7-24.1, SD 6.4]) and open repairs (10.8 mm [range 7.6-14.9, SD 2.7, P = .037]). The ultimate load at failure was not statistically different between the 2 repairs. CONCLUSIONS: A percutaneous ATR repair technique using endoscopic assistance and absorbable suture demonstrated low complications and good outcomes in a cohort of patients, with high satisfaction, and excellent functional outcomes including high rates of return to sport. Cadaveric biomechanical testing demonstrated excellent survival during testing and minimal increase in gapping compared with open repair technique, representing sufficient strength to withstand forces seen in early rehabilitation. A percutaneous Achilles tendon repair technique with absorbable suture may minimize risks associated with operative repair while still maintaining the benefit of operative repair. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Molecular weight distribution of raw and catalytic fast pyrolysis oils: comparison of analytical methodologies.

Comprehensive analysis of the molecular weight distribution of raw and catalytic fast pyrolysis oils derived from biomass remains a key technical hurdle to understanding oil quality as it relates to downstream use and multiple methods may be necessary to accurately represent all components present. Here, we report the molecular weight distribution metrics of fast pyrolysis (FP) and catalytic fast pyrolysis (CFP) oils as determined by gel permeation chromatography (GPC) combined with UV-diode array (UV), differential refractive index (RI), and multi-angle laser light scattering (MALS) detection. The measured molar mass distributions revealed that FP oil consisted of a higher proportion of larger products relative to the low molecular weight products contained in the CFP oil. GPC/RI and UV methods showed FP oil to have higher weight-average molecular weight (M w) and number-average molecular weight (M n) than CFP oil based on elution time. However, GPC/MALS, determined the two oils to have similar overall molecular weight distribution metrics (M w and M n) and yielded values significantly higher than those determined by RI and UV detectors relative to external standards. Overall, the use of a multiple detection GPC method could enable a more accurate comparison and determination of true molecular weight metrics of bio-oils.