Publication Bias in Upper Gastrointestinal Oncology Clinical Trials.

PURPOSE: Evidence-based medicine requires evaluation of the medical literature to guide clinical reasoning and treatment recommendations. The presence of publication bias towards exclusion of non-statistically significant clinical trials may be leading to an incomplete evaluation of the literature and cause potentially incomplete guidance for patients. We aimed to compare publication rates and impact of publications of positive and negative outcome clinical trials. METHODS: We queried the US National Library of Medicine Clinical Trials database identifying clinical trials with reported results on the topics of pancreatic, liver, and gastric cancer. A "positive" trial was defined as having a statistically significant difference between the treatment arms, while a "negative" did not. Data collected included termination cause, intervention, funding type, publication rates, and journal characteristics. RESULTS: In total, 535 clinical trials were examined, across all pathologies clinical trials with significant findings for the primary outcome were published at a higher rate (99%) compared to those with non-significant findings (77%) (p < 0.01). Significantly, more studies with significant findings reached at least 80% of their estimated enrollment goal versus non-significant studies, 72% and 53% respectively (p < 0.01). Three of four metrics for impact of publication showed no difference between significant and non-significant studies once they reached publication. CONCLUSION: These findings suggest that clinical trials of three of the most common upper gastrointestinal malignancies have a publication bias towards studies with significant primary outcome findings. This study has implications to the way evidence-based medicine is practiced as the medical literature appears to be failing to capture important data for consideration of clinical decision making.

Revisiting Level of Evidence Ratings in Plastic Surgery: A Call to Action.

BACKGROUND: Evidence-based medicine underpins medical and surgical practice, with level of evidence (LOE) being a key aspect that allows clinicians and researchers to better discriminate the methodological context by which studies are conducted and appropriately interpret their conclusions, and more specifically the strength of their recommendations. OBJECTIVES: The aim of this study was to reassess the LOE of articles published in plastic surgery journals. METHODS: To assess the overall LOE of publications from January 1 to December 31, 2021, a review of the following plastic surgery journals was performed: Aesthetic Surgery Journal (ASJ), Annals of Plastic Surgery (Annals), Journal of Plastic Reconstructive and Aesthetic Surgery (JRPAS), Plastic and Reconstructive Surgery (PRS), and Plastic and Reconstructive Surgery Global Open (PRS GO). RESULTS: Of 3698 PUBMED articles, 1649 original articles and systematic reviews were analyzed. The average LOE for each journal was: ASJ 3.02 ± 0.94, Annals 3.49 ± 0.62, JPRAS 3.33 ± 0.77, PRS 2.91 ± 0.77, and PRS GO 3.45 ± 0.70. The collective average LOE was 3.28 ± 0.78. Only 4.4% were LOE 1 and 7.3% were LOE 2. Compared to past studies, PRS showed a significant LOE improvement (P = .0254), while ASJ and JPRAS saw nonsignificant changes; Annals experienced a significant decrease (P = .0092). CONCLUSIONS: ASJ and PRS showed the highest LOE among the journals analyzed. Despite this, low LOE studies remain prevalent in plastic surgery. This paper serves as a call to action for both researchers and academic journals to elevate the standard, offering several strategies to help improve the LOE in plastic surgery.

Understanding Use of Real-World Data and Real-World Evidence to Support Regulatory Decisions on Medical Product Effectiveness.

RWE has potential to provide efficient and relevant information on the effectiveness of medical products, complementing the data generated in clinical trials; however, how RWE can support regulatory decision-making is unclear, potentially limiting its use. The objective of this study was to identify and characterize instances where RWE was included in the evidence package to support the effectiveness of a medical product regulated by U.S. Food and Drug Administration. A retrospective landscape analysis was conducted to identify instances where RWE was submitted to support effectiveness through targeted review of white and gray literature and publicly available FDA reviews of medical products. Trained evaluators examined FDA reviews to determine if and how RWE contributed to regulatory decision-making regarding effectiveness. Evaluators identified 34 instances of RWE submitted between 1954 and 2020, where 26% of instances were for oncology, 18% for hematology, and 12% for neurology. Over 50% of the products were indicated for use in rare disease or pediatric populations. 82% of products where RWE was submitted received an orphan designation. RWE was included in the product label in 59% of instances. Stated reasons indicating why submitted RWE did not significantly contribute to regulatory decision-making included lack of pre-specification of study design and analysis as well as data reliability and relevancy concerns. While there is historical use of RWE to support medical product effectiveness for oncology and rare diseases, potential exists to leverage the strengths of RWE to support other therapeutic areas and capture outcomes that are most relevant to patients.

Use of Real-World Data and Evidence in Drug Development of Medicinal Products Centrally Authorized in Europe in 2018-2019.

Real-world data/real-world evidence (RWD/RWE) are considered to have a great potential to complement, in some cases, replace the evidence generated through randomized controlled trials. By tradition, use of RWD/RWE in the postauthorization phase is well-known, whereas published evidence of use in the pre-authorization phase of medicines development is lacking. The primary aim of this study was to identify and quantify the role of potential use of RWD/RWE (RWE signatures) during the pre-authorization phase, as presented in the initial marketing authorization applications of new medicines centrally evaluated with a positive opinion in 2018-2019 (n = 111) by the European Medicines Agency (EMA). Data for the study was retrieved from the evaluation overviews of the European Public Assessment Reports (EPARs), which reflect the scientific conclusions of the assessment process and are accessible through the EMA website. RWE signatures were extracted into an RWE Data Matrix, including 11 categories divided over 5 stages of the drug development lifecycle. Nearly all EPARs included RWE signatures for the discovery (98.2%) and life-cycle management (100.0%). Half of them included RWE signatures for the full development phase (48.6%) and for supporting regulatory decisions at the registration (46.8%), whereas over a third (35.1%) included RWE signatures for the early development. RWE signatures were more often seen for orphan and conditionally approved medicines. Oncology, hematology, and anti-infectives stood out as therapeutic areas with most RWE signatures in their full development phase. The findings bring unprecedented insights about the vast use of RWD/RWE in drug development supporting the regulatory decision making.

Opioid Prescribing after Carpal Tunnel Release: Analysis from the Michigan Collaborative Hand Initiative for Quality in Surgery.

BACKGROUND: Little is known regarding the national practice patterns for postoperative opioid prescribing after carpal tunnel release, which is one of the most common surgical procedures performed. The authors sought to assess the rate of opioid prescribing after carpal tunnel release and patient-, surgeon-, and practice-level predictors of opioid prescriptions after surgery. METHODS: The authors conducted a cohort study from the Michigan Collaborative Hand Initiative for Quality in Surgery, a national consortium of nine practices with 33 surgeons who prospectively collect data for the purpose of quality improvement. Patients were included who underwent carpal tunnel release between July 1, 2019, and December 31, 2019. Multilevel logistic regression was used to determine practice and surgeon variation in postoperative opioid prescribing related to patient characteristics. RESULTS: Of the 648 patients with 792 operative hands, 52.9 percent were prescribed a postoperative opioid. After controlling for patient, surgeon, and practice characteristics, endoscopic carpal tunnel releases were associated with a decreased odds of receiving a postoperative opioid prescription compared to open carpal tunnel releases (OR, 0.19; 95 percent CI, 0.07 to 0.52). However, 57.4 percent of the variation in opioid prescribing was explained at the practice level, and 4.1 percent of the variation was explained at the surgeon level. CONCLUSIONS: Practice-level prescribing patterns play a substantial role in opioid prescribing. National efforts should consider development of evidence-based opioid prescribing recommendations for carpal tunnel release that target all prescribers, including trainees and advanced practice providers. In addition, endoscopic carpal tunnel release may offer an opportunity to minimize opioid prescribing. The authors recommend that providers encourage the use of nonopioid analgesia and limit opioid prescriptions after carpal tunnel release. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

2021 update of the AGIHO guideline on evidence-based management of COVID-19 in patients with cancer regarding diagnostics, viral shedding, vaccination and therapy.

The worldwide spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated infectious coronavirus disease (COVID-19) has posed a unique challenge to medical staff, patients and their families. Patients with cancer, particularly those with haematologic malignancies, have been identified to be at high risk to develop severe COVID-19. Since publication of our previous guideline on evidence-based management of COVID-19 in patients with cancer, research efforts have continued and new relevant data has come to light, maybe most importantly in the field of vaccination studies. Therefore, an update of our guideline on several clinically important topics is warranted. Here, we provide a concise update of evidence-based recommendations for rapid diagnostics, viral shedding, vaccination and therapy of COVID-19 in patients with cancer. This guideline update was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology by critically reviewing the currently available data on these topics applying evidence-based medicine criteria.

Utilization of systemic therapy for treatment of advanced urothelial carcinoma: Lessons from real world experience.

Metastatic bladder cancer has poor overall survival. Though systemic therapies have shown to improve overall survival, real-world studies have shown that more than half of the patients do not receive any systemic therapy, while only around 15-20% receive second-line therapy. Even in patients receiving systemic therapies a disproportionately higher use of carboplatin is observed in the first line despite proven superior effectiveness of cisplatin. Reasons for these observations include moderate effectiveness and relatively toxicity of platinum-based chemotherapy regimens, concerns with performance status and co-morbidities in this predominantly older patient population, communications barriers, lack of social support, and access to affordable healthcare. Herein we discuss potential ways to overcome these challenges which include (1) preventing/delaying metastatic disease by maximizing the receipt of neoadjuvant cisplatin-based therapy, and development of better tolerated and more effective neoadjuvant and adjuvant therapies, (2) use of avelumab maintenance therapy after 4-6 cycles of platinum-based chemotherapy to overcome attrition of patients from first to second-line therapy, (3) advancing effective and well-tolerated systemic therapies such as enfortumab vedotin, and erdafitinib to the first-line metastatic setting or even to the localized setting, (4) further development of effective and well-tolerated therapies like sacituzumab govitecan, a novel antibody-drug conjugate and (5) improving affordability and accessibility to systemic therapy agents.

Periprocedural complications in patients with SARS-CoV-2 infection compared to those without infection: A nationwide propensity-matched analysis.

BACKGROUND: Reports on emergency surgery performed soon after a COVID-19 infection that are not controlled for premorbid risk-factors show increased 30-day mortality and pulmonary complications. This contributed to a virtual cessation of elective surgery during the pandemic surge. To inform evidence-based guidance on the decisions for surgery during the recovery phase of the pandemic, we compare 30-day outcomes in patients testing positive for COVID-19 before their operation, to contemporary propensity-matched COVID-19 negative patients undergoing the same procedures. METHODS: This prospective multicentre study included all patients undergoing surgery at 170 Veterans Health Administration (VA) hospitals across the United States. COVID-19 positive patients were propensity matched to COVID-19 negative patients on demographic and procedural factors. We compared 30-day outcomes between COVID-19 positive and negative patients, and the effect of time from testing positive to the date of procedure (≤10 days, 11-30 days and >30 days) on outcomes. RESULTS: Between March 1 and August 15, 2020, 449 COVID-19 positive and 51,238 negative patients met inclusion criteria. Propensity matching yielded 432 COVID-19 positive and 1256 negative patients among whom half underwent elective surgery. Infected patients had longer hospital stays (median seven days), higher rates of pneumonia (20.6%), ventilator requirement (7.6%), acute respiratory distress syndrome (ARDS, 17.1%), septic shock (13.7%), and ischemic stroke (5.8%), while mortality, reoperations and readmissions were not significantly different. Higher odds for ventilation and stroke persisted even when surgery was delayed 11-30 days, and for pneumonia, ARDS, and septic shock >30 days after a positive test. DISCUSSION: 30-day pulmonary, septic, and ischaemic complications are increased in COVID-19 positive, compared to propensity score matched negative patients. Odds for several complications persist despite a delay beyond ten days after testing positive. Individualized risk-stratification by pulmonary and atherosclerotic comorbidities should be considered when making decisions for delaying surgery in infected patients.

Female Lower Urinary Tract Symptom Prevention and Treatment Strategies on Social Media: Mixed Correlation With Evidence.

OBJECTIVE: To evaluate the level of evidence behind recommendations on social media for disease prevention in five lower urinary tract symptoms. MATERIALS AND METHODS: We conducted a digital analysis of anonymous online posts on social media sites collected by a social media data mining service. One thousand posts about pelvic organ prolapse, stress urinary incontinence, overactive bladder, urinary tract infection, and interstitial cystitis/bladder pain syndrome were randomly selected. We analyzed these posts for recommendations regarding the prevention and treatment of these diseases, which were then compared to recommendations in available clinical guidelines and assessed for level of evidence. RESULTS: A total of 158 of 1000 posts contained 239 prevention strategies. For pelvic organ prolapse, there were 41 strategies identified, 25 (61%) of which had no evidence. For urinary tract infection 14 of 58 (29%) had no evidence, including recommendations for dietary modifications and urinary alkalization. For overactive bladder 8 of 28 (29%) had level 4 or no evidence. For stress urinary incontinence, 12 of 34 (36%) of prevention strategies had no evidence, such as laser rejuvenation and bladder training. Interstitial cystitis had the highest number of prevention strategies, and most were low or nonevidence based (70/79, 89%). CONCLUSION: Prevention and treatment strategies are common in online discussions of pelvic floor disorders, but at least one third of these recommendations have no evidential support. There is a role for further online education and social media engagement by health care specialists to promote evidence-based practices.

Benefits and limitations of real-world evidence: lessons from EGFR mutation-positive non-small-cell lung cancer.

While randomized controlled trials (RCTs) are the gold standard for evidence-based medicine, they do not always reflect real-world patient populations, limiting their generalizability and external validity. Real-world evidence (RWE), generated during routine clinical practice, is increasingly important in determining effectiveness outside of the tightly controlled conditions of RCTs, and is now recognized by regulatory bodies as a valuable complement to RCTs. Consequently, it is increasingly important for physicians to understand how RWE data can be used alongside clinical trial data. Here, we discuss the different types of real-world observational studies, outline the benefits and limitations of RWE, and, using examples from EGFR mutation-positive non-small-cell lung cancer, outline how RWE can be used to help inform treatment decisions.

Association Between a National Insurer's Pay-for-Performance Program for Oncology and Changes in Prescribing of Evidence-Based Cancer Drugs and Spending.

PURPOSE: Cancer drug prescribing by medical oncologists accounts for the greatest variation in practice and the largest portion of spending on cancer care. We evaluated the association between a national commercial insurer's ongoing pay-for-performance (P4P) program for oncology and changes in the prescribing of evidence-based cancer drugs and spending. METHODS: We conducted an observational difference-in-differences study using administrative claims data covering 6.7% of US adults. We leveraged the geographically staggered, time-varying rollout of the P4P program to simulate a stepped-wedge study design. We included patients age 18 years or older with breast, colon, or lung cancer who were prescribed cancer drug regimens by 1,867 participating oncologists between 2013 and 2017. The exposure was a time-varying dichotomous variable equal to 1 for patients who were prescribed a cancer drug regimen after the P4P program was offered. The primary outcome was whether a patient's drug regimen was a program-endorsed, evidence-based regimen. We also evaluated spending over a 6-month episode period. RESULTS: The P4P program was associated with an increase in evidence-based regimen prescribing from 57.1% of patients in the preintervention period to 62.2% in the intervention period, for a difference of +5.1 percentage point (95% CI, 3.0 percentage points to 7.2 percentage points; P < .001). The P4P program was also associated with a differential $3,339 (95% CI, $1,121 to $5,557; P = .003) increase in cancer drug spending and a differential $253 (95% CI, $100 to $406; P = .001) increase in patient out-of-pocket spending, but no significant changes in total health care spending ($2,772; 95% CI, -$181 to $5,725; P = .07) over the 6-month episode period. CONCLUSION: P4P programs may be effective in increasing evidence-based cancer drug prescribing, but may not yield cost savings.

Integration of partners of young women with cancer in oncofertility evidence-based informational resources.

Oncofertility has evolved over the years, with a prodigious amount of research documenting the importance of fertility for young patients with cancer, and the potential impact that fertility impairments due to cancer treatments has on their Quality of Life (QoL). Multiple professional bodies and scientific societies have included fertility as an integral part of clinical management. Clinical guidelines advocate that health professionals have the duty to discuss the risk of infertility and fertility preservation options as early as possible and refer to fertility specialists when appropriate. Collectively, fertility decisions are regarded as difficult for both patients and providers. Since providing fertility-related information is vital for better decision making, researchers and policy makers have concentrated their efforts in developing educational tools to aid decisions and guidelines to optimize the delivery of this information, focusing mainly on patients-providers and largely neglecting the role and influence that partners play in this process. Here, we reflect on the importance of partners in fertility decisions, with a focus on the provision of fertility-related information that is also geared towards partner. We highlight the need to involve partners in fertility discussions, and that their needs should be taken into account in both clinical guidelines and in the development of educational tools, for an optimal decision-making process.

Regional Anaesthesia Alone is Reasonable for Major Lower Extremity Amputation in High Risk Patients and May Initiate a More Efficacious Enhanced Recovery Programme.

OBJECTIVE: Major limb amputations are physiologically stressful and subject patients to peri-operative cardiovascular risk. Up to 90% of major lower extremity amputations (LEAMP) are being performed under general anaesthesia, despite regional anaesthesia being an acceptable option in most cases. Obtaining a better understanding of who would benefit from regional vs. general anaesthesia could reduce complications and help establish best evidence based practice. It was hypothesised that patients undergoing LEAMP with regional anaesthesia would have better post-operative outcomes than patients receiving general anaesthesia. METHODS: This retrospective cohort study used the U.S. Vascular Quality Initiative lower extremity amputation module to identify patients (≥18 years) who underwent LEAMP from 2013 to 2018. Outcomes included 30 day incidence of major adverse cardiac events (MACE) and all cause mortality. Multivariable logistic regression models were used to compute odds ratios (OR) and 95% confidence intervals (CI). Time to death was analysed using standard survival analysis. RESULTS: The final sample included 5 567 patients (median age: 65 years, 67% white, 65% male). Only 719 (13%) of patients received regional anaesthesia. Compared with patients undergoing general anaesthesia, patients in the regional group were older (67 vs. 65 years, p < .001) and more likely to have diabetes (78% vs. 69%; p < .001), end stage renal disease (26% vs. 18%; p < .001), congestive heart failure (33% vs. 27%; p < .01) and coronary artery disease (35% vs. 30%; p < .01). The overall incidence of MACE, death, and MACE or death was 5%, 6%, and 9%, respectively. There was no statistically significant difference by anaesthesia groups for MACE (OR 0.98, 95% CI 0.69-1.39) or mortality (HR 1.03, 95% CI 0.90-1.17). CONCLUSION: There was no difference in outcomes between regional or general anaesthesia techniques in patients undergoing LEAMP, despite the regional group having more comorbidities. Regional anaesthesia may be under used for high risk patients undergoing LEAMP. Further studies are needed to establish best practices in LEAMP procedures.

Drug treatments for covid-19: living systematic review and network meta-analysis

OBJECTIVE: To compare the effects of treatments for coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 1 December 2021 were included in the analysis. STUDY SELECTION: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. RESULTS: 463 trials enrolling 166 581 patients were included; 267 (57.7%) trials and 89 814 (53.9%) patients are new from the previous iteration; 265 (57.2%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, three drugs reduced mortality in patients with mostly severe disease with at least moderate certainty: systemic corticosteroids (risk difference 23 fewer per 1000 patients, 95% credible interval 40 fewer to 7 fewer, moderate certainty), interleukin-6 receptor antagonists when given with corticosteroids (23 fewer per 1000, 36 fewer to 7 fewer, moderate certainty), and Janus kinase inhibitors (44 fewer per 1000, 64 fewer to 20 fewer, high certainty). Compared with standard care, two drugs probably reduce hospital admission in patients with non-severe disease: nirmatrelvir/ritonavir (36 fewer per 1000, 41 fewer to 26 fewer, moderate certainty) and molnupiravir (19 fewer per 1000, 29 fewer to 5 fewer, moderate certainty). Remdesivir may reduce hospital admission (29 fewer per 1000, 40 fewer to 6 fewer, low certainty). Only molnupiravir had at least moderate quality evidence of a reduction in time to symptom resolution (3.3 days fewer, 4.8 fewer to 1.6 fewer, moderate certainty); several others showed a possible benefit. Several drugs may increase the risk of adverse effects leading to drug discontinuation; hydroxychloroquine probably increases the risk of mechanical ventilation (moderate certainty). CONCLUSION: Corticosteroids, interleukin-6 receptor antagonists, and Janus kinase inhibitors probably reduce mortality and confer other important benefits in patients with severe covid-19. Molnupiravir and nirmatrelvir/ritonavir probably reduce admission to hospital in patients with non-severe covid-19. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol is publicly available in the supplementary material. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fifth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

Trigger Finger Treatment: Identifying Predictors of Nonadherence and Cost.

BACKGROUND: Evidence-based practices in medicine are linked with a higher quality of care and lower health care cost. For trigger finger, identifying patient factors associated with nonadherence to evidence-based practices will aid physicians in treatment decisions. The objectives were to (1) determine patient factors associated with treatment nonadherence, (2) examine the success rates of steroid injections, and (3) evaluate the economic consequences of nonadherence to treatment recommendations. METHODS: The authors used data from the Clinformatics DataMart database from 2010 to 2017 to conduct a population-based analysis of patients with single-digit trigger finger. The authors calculated rates of steroid injection success and examined associations between injection success and patient factors using chi-square tests. In addition, the authors analyzed differences in the cost to the insurer, the cost to the patient, and total cost. RESULTS: A total of 29,722 patients were included in this analysis. Injection success rates were similar for diabetic (72 percent) and nondiabetic patients (73 percent), women (73 percent), and men (73 percent). Nonetheless, diabetics (OR, 1.4; 95 percent CI, 1.4 to 1.5; p < 0.001) and women (OR, 1.2; 95 percent CI, 1.1 to 1.2; p < 0.001) were significantly more likely to receive nonadherent treatment. In total, $23 million (U.S. dollars) were spent on nonadherent trigger finger care. CONCLUSIONS: Diabetics and women have increased odds of having surgery without a prior steroid injection, despite similar success rates of steroid injections compared to nondiabetics and men. Because performing surgical release before any steroid injections may represent a higher cost treatment option, providers should provide steroid injections before surgery for all patients regardless of diabetes status or sex to minimize overtreatment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Lessons from American Board of Plastic Surgery Maintenance of Certification Tracer Data: A 16-Year Review of Clinical Practice Patterns and Evidence-Based Medicine in Cleft Palate Repair.

BACKGROUND: As a component of the Maintenance of Certification process from 2003 to 2019, the American Board of Plastic Surgery tracked 20 common plastic surgery operations. By evaluating the data collected over 16 years, the authors are able to examine the practice patterns of pediatric/craniofacial surgeons in the United States. METHODS: Cumulative tracer data for cleft palate repair was reviewed as of April of 2014 and September of 2019. Evidence-based medicine articles were reviewed. Results were tabulated in three categories: pearls, or topics that were covered in both the tracer data and evidence-based medicine articles; topics that were covered by evidence-based medicine articles but not collected in the tracer data; and topics that were covered in tracer data but not addressed in evidence-based medicine articles. RESULTS: Two thousand eight hundred fifty cases had been entered as of September of 2019. With respect to pearls, pushback, von Langenbeck, and Furlow repairs all declined in use, whereas intravelar veloplasty increased. For items not in the tracer, the quality of studies relating to analgesia is among the highest of all areas of study regarding cleft palate repair. In terms of variables collected by the tracer but not studied, in 2019, 41 percent of patients received more than 1 day of antibiotics. CONCLUSIONS: This article provides a review of cleft palate tracer data and summarizes the research in the field. Review of the tracer data enables cleft surgeons to compare their outcomes to national norms and provides an opportunity for them to consider modifications that may enhance their practice.

Evaluation of a Comprehensive Skin Toxicity Program for Patients Treated With Epidermal Growth Factor Receptor Inhibitors at a Cancer Treatment Center.

Importance: Up to 90% of patients treated with an epidermal growth factor receptor inhibitor (EGFRi) experience cutaneous toxic effects that are negatively associated with quality of life and lead to treatment interruptions. The Skin Toxicity Evaluation Protocol With Panitumumab trial found reduced incidence of skin toxicity and quality of life impairment with preemptive use of doxycycline hyclate, topical corticosteroids, moisturizers, and sunscreen, demonstrating the benefit of prophylactic treatment for skin toxicity. Objective: To evaluate the association of a comprehensive skin toxicity program with adherence to prophylaxis guidelines for the prevention of EGFRi-associated cutaneous toxic effects. Design, Setting, and Participants: A retrospective cohort study was conducted of all adult patients receiving at least 1 dose of cetuximab at the Dana-Farber Cancer Institute in the calendar year 2012 (2 years after publication of the Skin Toxicity Evaluation Protocol With Panitumumab) or the calendar year 2017 (2 years after full implementation of the Skin Toxicities from Anticancer Therapies program). Main Outcomes and Measures: Primary outcomes were rate of preemptive rash treatment and selection of preemptive agents. Secondary outcomes were incidence of rash, rates of rescue treatments, rates of cetuximab dose changes or interruptions, and overall survival at 2 years. Results: There were 118 patients (85 men; median age, 62.4 years [range, 23.5-91.7 years]) treated with cetuximab in 2012 and 90 patients (70 men; median age, 62.5 years [range, 30.7-90.5 years]) treated with cetuximab in 2017; 11 patients (9%) in 2012 and 31 patients (34%) in 2017 were treated at Dana-Farber Cancer Institute affiliate sites. At cetuximab treatment initiation, 29 patients (25%) in 2012 and 42 patients (47%) in 2017 were prophylactically treated for skin toxicity (P < .001). From 2012 to 2017, preemptive tetracycline use (13 of 29 [45%] to 30 of 42 [71%]; P = .02) and topical corticosteroid use (2 of 29 [7%] to 24 of 42 [57%]; P < .001) increased and topical antibiotic use (23 of 29 [79%] to 18 of 42 [43%]; P = .002) decreased. There was no significant difference in incidence of rash by prophylaxis status. Patients prescribed prophylactic treatment were 94% less likely to require a first rescue treatment for rash (adjusted odds ratio, 0.06; 95% CI, 0.02-0.16; P < .001), 74% less likely to require a second rescue treatment for rash (adjusted odds ratio, 0.26; 95% CI, 0.08-0.83; P = .02), and 79% less likely to experience a cetuximab dose change or interruption (adjusted odds ratio, 0.21; 95% CI, 0.06-0.81; P = .02) than patients not prescribed prophylactic treatment, adjusting for treatment site and year. Conclusions and Relevance: Dermatologists can add value to oncology care by raising awareness of appropriate treatment options and increasing adherence to evidence-based prophylaxis protocols for EGFRi-associated rash, which is associated with decreased interventions and toxicity-associated chemotherapy interruptions.

Epidemiological guideline influence on the therapeutic trend and patient outcome of uterine cervical cancer in Japan: Japan society of gynecologic oncology guideline evaluation committee project.

OBJECTIVE: The Japan Society of Gynecologic Oncology published its first clinical guidelines for uterine cervical cancer in 2007 which has been revised twice in 2011 and 2017. The aim of this study was to investigate the influence of the first guideline publication on the therapeutic trend and patient outcome by analyzing uterine cervical cancer cases registered to the cancer registry organized by the Japan Society of Obstetrics and Gynecology. METHODS: Data of uterine cervical cancer cases registered to the cancer registry from 2000 to 2012 were provided. Epidemiological and clinical trend were analyzed by the Chi-squared test with subsequent standardized residual analysis. Overall survival among the patients registered between 2004 and 2009 was analyzed using the Fine and Gray competing risk model. RESULTS: 68,707 cases were registered during the study period. A trend analysis revealed that the guideline publication may have led to a decrease in neoadjuvant chemotherapy in parallel with an increase in radiation therapy mainly in stage II and III patients undergoing primary treatment. A survival analysis indicated that the introduction of the guideline may have improved overall survival among stage III uterine cervical cancer patients, even though a significant difference was not observed in all of the cases. CONCLUSIONS: This study demonstrated the potential influence of the guideline publication on the clinical trend and patient outcome. As this is the first assessment of the guideline for uterine cervical cancer in Japan, continuous evaluation is necessary to further comprehend the significance of this guideline.