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Atopic dermatitis is a prevalent condition in children and can be effectively managed with medications such as topical calcineurin inhibitors (pimecrolimus or tacrolimus). A key unresolved safety concern is whether use of topical calcineurin inhibitors is associated with cancer. We systematically reviewed the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors.As part of the 2022 American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters atopic dermatitis guidelines, we searched MEDLINE, Embase, the Latin American and Caribbean Health Sciences Literature database, the Índice Bibliográfico Espanhol de Ciências da Saúde database, the Global Resource of Eczema Trials database, WHO's International Clinical Trials Registry Platform, the US Food and Drug Administration database, the European Medicines Agency database, company registers, and relevant citations from inception to June 6, 2022. We included randomised controlled trials and comparative and non-comparative non-randomised studies in any language addressing cancer risk in patients with atopic dermatitis using topical calcineurin inhibitors. We excluded split-body studies and studies with less than 3 weeks of follow-up. Paired reviewers independently screened records, extracted data, and assessed risk of bias in duplicate. We used Bayesian models to estimate the probability for cancer due to topical calcineurin inhibitor exposure and the GRADE approach to determine the certainty of the evidence. Patients, advocacy groups, and care providers set a priori thresholds of important effects. This study is registered with Open Science Framework, https://osf.io/v4bfc.We identified and analysed 110 unique studies (52 randomised controlled trials and 69 non-randomised studies [11 were non-randomised study extensions of randomised controlled trials]) including 3·4 million patients followed up for a mean of 11 months (range 0·7-120). The absolute risk of any cancer with topical calcineurin inhibitor exposure was not different from controls (absolute risk 4·70 per 1000 with topical calcineurin inhibitors vs 4·56 per 1000 without; odds ratio 1·03 [95% credible interval 0·94-1·11]; moderate certainty). For all age groups and using data from observational studies and randomised controlled trials, the use of pimecrolimus (OR 1·05 [95% credible interval 0·94-1·15]) or tacrolimus (0·99 [0·89-1·09]) is likely to have had little to no association with cancer compared with no topical calcineurin inhibitor exposure. For pimecrolimus versus tacrolimus, the finding was similar (0·95 [95% credible interval 0·83-1·07]). Findings were similar in infants, children, and adults, and robust to trial sequential, subgroup, and sensitivity analyses.Among individuals with atopic dermatitis, moderate-certainty evidence shows that topical calcineurin inhibitors do not increase the risk of cancer. These findings support the safe use of topical calcineurin inhibitors in the optimal treatment of patients with atopic dermatitis.American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology via the Joint Task Force on Practice Parameters.

Objectives This study aimed to investigate how value is defined and measured in existing value assessment frameworks (VAFs) in healthcare. Methods We searched PubMed, Embase, the Cochrane Library, and Centre for Reviews and Dissemination from 2008 to 2019. We also performed backward citation chaining of included studies and previously published systematic reviews. Studies reporting the development of a VAF in healthcare were included. For each included framework, we extracted and compared the context, target users, intended use, methods used to identify value attributes, description of the attributes, and attribute scoring approaches. Results Of the 8151 articles screened, 57 VAFs were included. The value attributes included in 55 VAFs were grouped into 9 categories: health benefits (n = 53, 96%), affordability (n = 45, 82%), societal impact (n = 42, 76%), burden of disease (n = 36, 65%), quality of evidence (n = 32, 58%), cost-effectiveness (n = 31, 56%), ethics and equity (n = 27, 49%), unmet needs (n = 21, 38%), and innovation (n = 15, 27%). The remaining 2 VAFs used broad attributes or user-defined attributes. Literature review was the main approach to identify value attributes in 36 VAFs. Patient or public was engaged through the development of only 11 VAFs. Weighting has been used to score 29 VAFs, of which 19 used the methods of multicriteria decision analysis. Conclusions There are substantial variations in defining and measuring value. A noticeable weakness of existing VAFs is that patient or public engagement was generally very limited or missing in framework development process. Existing VAFs tend to aggregate multiple value attributes into a single index for decision making.

Cardiac surgery is performed worldwide to treat severe cases of cardiovascular diseases. Statins have shown controversial effects on complications after cardiac surgeries. We aimed to investigate the effect of preoperative statin therapy on the frequency of postoperative mortality, renal, and neurological complications.In a retrospective cohort study, the database of patients operated on in two hospitals in southern Iran during 2008-2019 was used to compare preoperative statin use with no use on the composite outcome of mortality, renal, and neurological complications as well as on each component of the composite, separately. Effects of low dose (40 mg simvastatin equivalence) vs. high dose (≥40 mg) statins were also evaluated. Confounders that could affect the outcomes were considered in the logistic regression model, and multiple imputation techniques were used to categorize patients with unknown statin dose use as either high or lowdose users.Of total 7329 patients, 17.6% of statin users and 17% of non-statin users developed the composite outcome (P=0.51). Statin use had no statistically significant association with the composite outcome (aRR 1.01 [95% CI: 0.88-1.16]). There was no significant association with mortality [aRR: 0.75 (95% CI: 0.34-1.69)], neurological [aRR: 1.25 (95% CI: 0.77-2.12)], or renal complications [aRR: 1.03 (95% CI 0.90-1.19)] after surgery. Neither low nor high doses had any statistically significant effect on the composite or any of its components.In this large study, preoperative statin use, either high dose or low dose, did not affect short-term postoperative mortality, neurological, or renal complications.

Atopic dermatitis affects millions worldwide and is effectively managed by topical treatments, including topical calcineurin inhibitors, pimecrolimus and tacrolimus. In 2005 and 2011, the FDA released reviews associating topical calcineurin inhibitors with a theoretical cancer risk, albeit an uncertain association. We systematically reviewed the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors. We systematically identified randomized controlled trials, comparative, and non-comparative non-randomized studies from database inception to 6 June 2022, from MEDLINE, EMBASE, GREAT, LILACS, ICTRP, FDA, EMA, company registers and relevant citations. We included studies in any language addressing the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors for greater than 3 weeks. We excluded split-body studies. We conducted a Bayesian meta-analysis and used the GRADE approach to determine the certainty of the evidence. A multidisciplinary panel including patients, advocacy groups and care providers, set an a priori threshold of 1 in 1000 risk difference as a clinically important effect. We analysed 121 studies (52 randomized controlled trials and 69 non-randomized studies) including 3.4 million patents followed for a mean of 11 months (range: 0.7–120). The absolute risk of any cancer with topical calcineurin inhibitor exposure was neither different from controls (absolute risk 4.70 per 1000 with topical calcineurin inhibitor exposure vs. 4.56 per 1000 without; odds ratio 1.03 [95% credible interval 0.94–1.11], moderate-certainty evidence) nor the general US population (4.6 per 1000). Findings were similar in infants, children, and adults, and were robust to trial sequential, subgroup and sensitivity analyses. Among infants, children and adults with atopic dermatitis, moderate-certainty evidence shows that topical calcineurin inhibitors do not increase the risk of cancer. These findings support the safe use of topical calcineurin inhibitors in the management of patients with atopic dermatitis. Our findings provide actional information to inform updated clinical practice guidelines, product labels and continuing education for care providers, to clarify the safe usage of topical calcineurin inhibitors.

Evaluating the relevance of published health utilities to the context of a cost-utility analysis (CUA) remains an essential, yet often overlooked, task. The objective of this study was to provide guidance on this process through the development of the Health utility Application Tool (HAT). We conducted semi-structured telephone interviews with Canadian stakeholders from reimbursement bodies, academia, and the pharmaceutical industry to identify current practices and perspectives of the application of the health utility literature to CUAs. An online survey with international members of the general health economics and outcomes research community was also conducted to gather opinions on key concepts. Based on the themes emerging from the interviews and online questionnaire, the HAT includes questions prompting investigators to consider the following constructs: similarity of the clinical condition in the health utility study and the CUA; similarity of health utility study participant demographics and the demographics of the CUA’s target population; similarity of the health state descriptions in the health utility study and the CUA; and the method of assigning utility weights. Considerations of transparency prompted additional items, including: means by which the health utility study was identified; type of respondents; study design; and measure used to collect health utility estimates. The HAT is intended to guide the evaluation of the applicability of published health utilities for a CUA, thus promoting transparency and accountability in the selection of model inputs.

Objective To replace educational opportunities lost during the coronavirus disease 2019 (COVID-19) pandemic, the Department of Neurosurgery at Lenox Hill Hospital produced an open-access webinar series (“BRAINterns”) that covered a broad range of health care topics with a focus on neurosurgery. Methods This 8-week webinar series ran from July 1 to August 28, 2020. An optional exit survey was distributed to participants. Data were analyzed to characterize and better understand trends among a global cohort of participants. Results A total of 16,484 people registered for BRAINterns, and 6675 took the survey (40.5% response rate). Responders represented 87 countries, of which the majority were from the United States and Canada (90.48%, n = 6039). Responders were primarily female (82.9%, n = 5521). Racial and ethnic representation was majority Asian (42%, n = 2798), followed by White (22.7%, n = 1514), Hispanic/Latino (16.2%, n = 1080), and Black and African American (7.7%, n = 516). Participants reported hearing about BRAINterns through various social media platforms (72.18%, n = 4818)—the most popular was TikTok (33.4%, n = 2232). Overall, 93.4% of participants reported that the course was a good use of their time during the pandemic, and 86.7% reported that the course helped replace lost opportunities. Conclusions These data demonstrate that webinar-based education is an effective method of expanding access to careers in medicine and in particular, neurosurgery, to traditionally underrepresented populations. Social media can be a powerful tool to combat barriers to early exposure and vastly improve diversity within the field.

Published health utility studies are increasingly cited in cost–utility analyses to inform reimbursement decision-making. However, there is limited guidance for investigators looking to systematically evaluate the methodological quality of health utility studies or their applicability to decision contexts. To describe how health utility concepts are reflected in tools intended for use with the health economic literature, particularly with respect to the evaluation of methodological quality and context applicability. We reviewed the critical appraisal and reporting tools described in a 2012 report published by the Agency for Healthcare Research and Quality (AHRQ), supplemented with a keyword search of MEDLINE and EMBASE, to identify existing tools which include health utility constructs. From these tools, a list of relevant items was compiled and grouped into domain categories based on the methodological or applicability aspect they were directed toward. Of the 24 tools we identified, 12 contained items relevant to the evaluation of health utilities. Sixty-five items were considered relevant to the evaluation of quality, while 44 were relevant to the evaluation of applicability. Items were arranged into four domains: health state descriptions; selection and description of respondents; elicitation and measurement methods; and other considerations. As key inputs to cost–utility analyses, health utilities have the potential to significantly impact estimates of cost-effectiveness. Existing tools contain only general items related to the conduct or use of health utility studies. There is a need to develop tools that systematically evaluate the methodological quality and applicability of health utility studies.

Summary Objective The contributions of intervertebral disc disease and subject-specific covariates to systemic inflammation in low back pain are unknown. We examined the effects of symptomatic disc herniation (DH) and MRI herniation severity on serum cytokine levels in clinical subjects. Design Cytokine levels from lumbar DH subjects (N = 78) were compared to control subjects (N = 57) accounting for effects of DH, age, body mass index (BMI) and gender. Effect of DH severity on cytokine levels was analyzed on subsets of subjects with acute or chronic pain. Serum cytokines were also analyzed in a subset of patients between pre- and 3 months post-surgery. Results Cytokine levels were elevated in the serum of patients with symptomatic DH, and the covariates age, BMI and gender significantly contributed to levels of some cytokines. Severity of herniation was a significant contributor to pain intensity (VAS), serum levels of HMGB1, PDGFbb, and IL-9. The relationship between DH severity and cytokine levels was confirmed in subjects with chronic, but not acute symptoms. Serum levels of macrophage migration inhibitory factor (MIF) decreased, whereas levels of CCL3, CCL11, CXCL1, and CXCL10 were significantly elevated post surgery. Conclusions This study is the first to show that DH severity is coordinately associated with changes in serum levels of inflammatory cytokines in chronic pain subjects. HMGB1, PDGFbb and IL-9 are novel mediators of increasing DH severity, indicative of cellular damage, neuro-inflammation and angiogenesis. Resolution of inflammation was observed with decrease in MIF post surgery. However, elevated chemokine levels indicate ongoing remodeling and wound healing at 3-month time point.

Background The coronavirus disease 2019 (COVID-19) pandemic has infected more than 13 million people on a global scale and claimed more than half million deaths across 213 countries and territories. While the focus is currently on recovery from the pandemic, the disease has significantly changed the way we practice medicine and neurosurgery in New York City and the United States. Apart from the emergency cases, several health systems across the country have similarly started to perform elective surgeries. Although COVID-19 screening and testing guidelines have been proposed and adopted by many hospitals, these may not adequately protect the operating room personnel who are in proximity to the patient for prolonged periods. There are concerning reports of especially high transmission rates of COVID-19 in transmucosal head and neck procedures conducted by otolaryngologists and neurosurgeons, despite attempts at wearing what constitutes appropriate personal protective equipment. Methods Here, we describe a simple technique of additional draping that can be used for all cranial, endonasal, spinal, and neurointerventional cases to limit the transmission of coronavirus. Results The proposed technique offers a simple, commonly available, cost-effective alternative that avoids the use of additional retractor systems. Moreover, this technique can be used in all neurosurgical procedures. Conclusions With the rising concerns regarding airborne spread of the virus, we expect that these precautions will prove highly useful as we enter the recovery phase of this pandemic and hospitals attempt to prevent a return to widespread infection. In addition, its availability and cost effectiveness make this technique especially attractive to practical use in centers with limited resources.

Background Concordance between Common Drug Review (CDR) recommendations and provincial plans has been studied previously. However, no study has, to the best of the authors' knowledge, examined the characteristics of CDR recommendations that may be associated with concordance. Methods Recommendation-decision pairs were collected from the CDR and the provincial plans of Ontario, British Columbia and Alberta. Concordance was evaluated by province. Characteristics of each CDR recommendation were collected, and associations with concordance were evaluated by logistic regression. Results Recommendation-listing concordance was high. Positive references to cost and clinical outcomes compared to placebo were statistically associated with concordance. Negative references to cost and to the consistency and certainty of economic evidence were statistically associated with discordance. However, these findings were inconsistent across the jurisdictions studied. Conclusion Although concordance was high, the ability of recommendation characteristics to explain the relationship between province and CDR listing decisions was limited. This exploratory study highlights the complexity of the reimbursement process and possible reasons for drug listing differences across jurisdictions.

Objective To examine the frequency of, and risk factors for, disease flare following COVID-19 vaccination in patients with systemic rheumatic disease (SRD). Methods An international study was conducted from 2 April to 16 August 2021, using an online survey of 5619 adults with SRD for adverse events following COVID-19 vaccination, including flares of disease requiring a change in treatment. We examined risk factors identified a priori based on published associations with SRD activity and SARS-CoV-2 severity, including demographics, SRD type, comorbidities, vaccine type, cessation of immunosuppressive medications around vaccination and history of reactions to non-COVID-19 vaccines, using multivariable logistic regression. Results Flares requiring a change in treatment following COVID-19 vaccination were reported by 4.9% of patients. Compared with rheumatoid arthritis, certain SRD, including systemic lupus erythematosus (OR 1.51, 95% CI 1.03, 2.20), psoriatic arthritis (OR 1.95, 95% CI 1.20, 3.18) and polymyalgia rheumatica (OR 1.94, 95% CI 1.08, 2.48) were associated with higher odds of flare, while idiopathic inflammatory myopathies were associated with lower odds for flare (OR 0.54, 95% CI 0.31–0.96). The Oxford-AstraZeneca vaccine was associated with higher odds of flare relative to the Pfizer-BioNTech vaccine (OR 1.44, 95% CI 1.07, 1.95), as were a prior reaction to a non-COVID-19 vaccine (OR 2.50, 95% CI 1.76, 3.54) and female sex (OR 2.71, 95% CI 1.55, 4.72). Conclusion SRD flares requiring changes in treatment following COVID-19 vaccination were uncommon in this large international study. Several potential risk factors, as well as differences by disease type, warrant further examination in prospective cohorts.

BackgroundWe describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine.MethodsFrom 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination.ResultsWe analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%.ConclusionAmong adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.

Introduction The present study aimed to obtain Canadian stakeholders' feedback on a list of proposed recommendations for updating the Patented Medicine Prices Review Board (PMPRB)'s 2007 budget impact analysis (BIA) guidelines. Methods A mixed-methods study was designed to obtain feedback from two stakeholder perspectives-(public and private) payers and manufacturers-on the proposed BIA recommendations. We obtained policymakers' opinion through one-on-one interviews and collected feedback from manufacturers and their consultants using a survey. The interview guide and the survey were developed based on the list of recommendations related to BIA key elements, which were either not discussed or addressed differently in the PMPRB 2007 BIA guidelines. The list was derived from 16 Canadian or other national and transnational BIA guidelines. A thematic analysis was applied for analysis of the qualitative (interview) data. Results Thirty-five policymakers and manufacturers participated in the study. Stakeholders supported the inclusion of 56% of the proposed recommendations into the guidelines pertaining to the use of expert opinions, data extrapolated from the payers' database, scenario analysis, and dynamic population. Inclusion of indirect costs, and cost transfers from other jurisdictions, were not approved. There was no consensus regarding the inclusion of patients' adherence/compliance and cost offsets. Conclusions The present study has provided sufficient insights to enable the creation of a penultimate version for updating the PMPRB BIA guidelines. This penultimate version will be subject to a broader consultation among stakeholders prior to a final revision and approval. Further Canadian stakeholder feedback is required for reaching consensus on inconclusive recommendations.

Background and Objectives Forest plots are an important graphical method in meta-analyses used to show results from individual studies and pooled analyses. Forest plots are easy and straightforward to understand because they provide tabular and graphical information about estimates of comparisons or associations, corresponding precision, and statistical significance. This visual representation also makes it easier to see variations between individual study results. Forest plots are widely used in not only systematic reviews and meta-analyses but also observational studies and clinical trials. In this study, we aimed to show readers the various uses of forest plots in displaying analysis results. Study Design and Setting We used a tutorial type to show multiple uses of forest plots in meta-analyses, clinical trials, and observational studies according to the PICO (Population or Subgroup, Intervention or Exposure, Control, and Outcome) framework. Results We introduced forest plots' structure, application, current practice, and research advances in health research. We provided some examples from the literature to show the various uses of forest plot–type graphics in health research including meta-analyses, clinical trials, and observational studies. Conclusion It is expected that our discussion of the current multiple uses of forest plots in meta-analyses, clinical trials, and observational studies provides a glimpse about their potential in displaying results in a way that makes comparisons between items easier.

Aims To identify and evaluate clinical pharmacology (CP) online curricular (e-Learning) resources that are internationally available for medical students. Methods Literature searches of Medline, EMBASE and ERIC databases and an online survey of faculty members of international English language medical schools, were used to identify CP e-Learning resources. Resources that were accessible online in English and aimed to improve the quality of prescribing specific medications were then evaluated using a summary percentage score for comprehensiveness, usability and quality, and for content suitability. Results Our literature searches and survey of 252 faculty (40.7% response rate) in 219 medical schools identified 22 and 59 resources respectively. After screening and removing duplicates, 8 eligible resources remained for evaluation. Mean total score was 53% (standard deviation = 13). The Australian National Prescribing Curriculum, ranked highest with a score of 77%, based primarily on very good ratings for usability, quality and suitable content. Conclusion Using a novel method and evaluation metric to identify, classify, and rate English language CP e-Learning resources, the National Prescribing Curriculum was the highest ranked open access resource. Future work is required to implement and evaluate its effectiveness on prescribing competence.

The Canadian budget impact analysis (BIA) guidelines were published by the Patented Medicine Prices Review Board (PMPRB) in 2007. Some Canadian federal, provincial and territorial (F/P/T) drug plans have updated their BIA guidelines since then. The aim of the present review was to provide a comprehensive list of the key BIA recommendations from the various Canadian F/P/T drug plans and private payers and to highlight the differences between those guidelines and the recommendations that were in the Canadian PMPRB 2007 BIA guidelines. We searched the websites of fifteen F/P/T public drug benefit programs including the Canadian Agency for Drugs and Technologies in Health (CADTH) and Non-Insured Health Benefits Program (NIHBP) and five private payers’ websites. An Excel-based data abstraction form was designed to highlight differences between recommendations relating to the BIA key elements made by different guidelines. Eight BIA guidelines (PMPRB 2007, Alberta, British Columbia, Manitoba, Ontario, Quebec, CADTH, and Medavie Blue Cross) were identified and reviewed, and a comprehensive list of recommendations was abstracted. Recommendations were similar to the 2007 guidelines in terms of time horizon duration, comparators, target population assessment and use of direct drug costs in BIAs. Differences were mostly related to actual acquisition cost, such as whether or not to include markups and dispensing fees, the patients’ perspective, cost of supplies, cost of health care utilization, and scenario analysis. The recommendations that were not included in the PMPRB 2007 guidelines but were included in at least one of the Canadian F/P/T or private guidelines were related to the inclusion of the patients’ perspective (i.e., co-payment), the costing, the handling of uncertainty and the reporting format. The present study is a comparative review of recommendations between the Canadian PMPRB 2007 guidelines and the F/P/T or private payers’ BIA guidelines, and provides a most up-to-date list of recommendations for revising the Canadian BIA guidelines, with applicability for both public and private plan new drug submissions in Canada.

Background: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide. Methods: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis. Findings: 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjogren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514). Interpretation: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity. Funding: American College of Rheumatology.

Calculating the number needed to treat (NNT) has been widely used to help understand treatment effect results of randomized controlled trials (RCTs). Combined benefit and harm profiles from RCT results have to be taken into account to maximize benefits and minimize harms. Unfortunately, in the biomedical community, there is no easy and acceptable way to incorporate both benefit and harm information of treatments in a single summary statistic similar to an NNT. In this study, we propose a new metric, the “NNT for net effect” or NNTnet to present the combined benefit and harm effects of an intervention or therapy based on NNT-type information with the intention that it will advance decision-making for health professionals, researchers, and resource managers in real-world practice. Examples are provided to illustrate the calculation and application of the NNTnet in practice. An NNTnet is specifically applicable to the physicians and resource managers who interpret the data published in the literature to help with their decision-making and the researchers who present the trial data to the audiences in their studies and presentations, all of whom used to use NNT information to show and interpret beneficial and harmful effects separately.

Published health utility studies are increasingly cited in cost-utility analyses to inform reimbursement decision-making. However, there is limited guidance for investigators looking to systematically evaluate the methodological quality of health utility studies or their applicability to decision contexts.To describe how health utility concepts are reflected in tools intended for use with the health economic literature, particularly with respect to the evaluation of methodological quality and context applicability.We reviewed the critical appraisal and reporting tools described in a 2012 report published by the Agency for Healthcare Research and Quality (AHRQ), supplemented with a keyword search of MEDLINE and EMBASE, to identify existing tools which include health utility constructs. From these tools, a list of relevant items was compiled and grouped into domain categories based on the methodological or applicability aspect they were directed toward.Of the 24 tools we identified, 12 contained items relevant to the evaluation of health utilities. Sixty-five items were considered relevant to the evaluation of quality, while 44 were relevant to the evaluation of applicability. Items were arranged into four domains: health state descriptions; selection and description of respondents; elicitation and measurement methods; and other considerations.As key inputs to cost-utility analyses, health utilities have the potential to significantly impact estimates of cost-effectiveness. Existing tools contain only general items related to the conduct or use of health utility studies. There is a need to develop tools that systematically evaluate the methodological quality and applicability of health utility studies.

OBJECTIVE We aimed to explore whether frailty was associated with fracture risk and whether frailty could modify the propensity of type 2 diabetes toward increased risk of fractures. RESEARCH DESIGN AND METHODS Data were from a prospective cohort study. Our primary outcome was time to the first incident clinical fragility fracture; secondary outcomes included time to hip fracture and to clinical spine fracture. Frailty status was measured by a Frailty Index (FI) of deficit accumulation. The Cox model incorporating an interaction term (frailty × diabetes) was used for analyses. RESULTS The analysis included 3,149 (70% women) participants; 138 (60% women) had diabetes. Higher bone mineral density and FI were observed in participants with diabetes compared with control subjects. A significant relationship between the FI and the risk of incident fragility fractures was found, with a hazard ratio (HR) of 1.02 (95% CI 1.01–1.03) and 1.19 (95% CI 1.10–1.33) for per-0.01 and per-0.10 FI increase, respectively. The interaction was also statistically significant (P = 0.018). The HR for per-0.1 increase in the FI was 1.33 for participants with diabetes and 1.19 for those without diabetes if combining the estimate for the FI itself with the estimate from the interaction term. No evidence of interaction between frailty and diabetes was found for risk of hip and clinical spine fractures. CONCLUSIONS Participants with type 2 diabetes were significantly frailer than individuals without diabetes. Frailty increases the risk of fragility fracture and enhances the effect of diabetes on fragility fractures. Particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.

Background The Coronavirus disease 2019 (COVID-19) outbreak has left a lasting mark on medicine globally. Methods Here we outline the steps that the Lenox Hill Hospital/Northwell Health Neurosurgery Department—located within the epicenter of the pandemic in New York City—is currently taking to recover our neurosurgical efforts in the age of COVID-19. Results We outline measurable milestones to identify the transition to the recovery period and hope these recommendations may serve as a framework for an effective path forward. Conclusions We believe that recovery following the COVID-19 pandemic offers unique opportunities to disrupt and rebuild the historical patient and office experience as we evolve with modern medicine in a post–COVID-19 world.

Introduction Budget impact analysis (BIA) in health care, sometimes referred to as resource impact, is the financial change in the use of health resources associated with adding a new drug to a formulary or the adoption of a new health technology. Several national and transnational organizations worldwide have updated their BIA guidelines in the past 4 years. The aim of the present review was to provide a comprehensive list of the key recommendations of BIA guidelines from different countries that may be of interest for those who wish to build or to update BIA guidelines. Methods National and transnational BIA guidelines were searched in databases including MEDLINE, EMBASE, Cochrane, EconLit, CINAHL, Business Source Premier, HealthSTAR, and the gray literature including regulatory agency websites. Data were reviewed and abstracted based on key elements in a standard BIA model (analytical model structure, input and data sources, and reporting format). Results Eight national (Australia, UK, Belgium, Ireland, France, Poland, Brazil, and Canada) and one transnational (International Society for Pharmacoeconomics and Outcomes Research) BIA guidelines were included in this review, and a comprehensive list of BIA recommendations was identified. The review showed that certain recommendations such as patient population assessment, drug-related direct costs, discounting, and disaggregated results were common across the various jurisdictions. BIA guidelines differed from each other in terms of the number and scope of recommendations, the terminology used (eg, the definition of comparators or cost offsets) and the direction of the recommendations (ie, to include or not to include with respect to such items as off-label indications, indirect costs, clinical outcomes, and resource utilization). Conclusion While there was a common purpose for all of the BIA guidelines that were identified, substantial differences did occur in the specific recommendations. The pharmaceutical financing system structure might explain why guidelines from the UK, Australia, and Canada have more country-specific recommendations. The desire to be consistent with adopted economic evaluation assumptions might be another reason for some observed differences between countries. Further research is required to assess the source of the heterogeneity between BIA recommendations are identified in different guidelines.

Intervertebral disc (IVD) degeneration (DD) is associated with low back pain, the leading cause of disability worldwide. Damage-associated molecular patterns (DAMPs) that contribute to inflammation and trigger DD have not been well characterized. Extracellular high mobility group box-1 (HMGB1) protein has been implicated as a potent DAMP and pro-inflammatory stimulus in the immune system. In this study, we show that HMGB1 and IL-6 levels increase in patients with advanced DD in comparison to early DD. This study further tested the hypothesis that HMGB1 promotes inflammatory signaling driving DD in human nucleus pulposus (NP) cells and tissue. Immunofluorescence and western blot analysis confirmed the expression of HMGB1 and its extracellular release by NP cells under cell stress. Gene expression and protein quantification indicate that HMGB1 stimulates the expression IL-6 and MMP-1 in a dose-dependent manner. The contributions of toll-like receptor (TLR) -2, -4 and receptor for advanced glycation end products (RAGE) as receptors mediating HMGB1 signaling was examined using small molecule inhibitors. Inhibition of TLR-4 signaling, with TAK-242, completely abrogated HMGB1 induced IL-6 and MMP-1 expression, whereas inhibition of TLR-2, with O-vanillin, or RAGE, with FPS-ZM1, had mild inhibitory effects. HMGB1 stimulation activated NF-ĸB signaling while TAK-242 co-treatment abrogated it. Lastly, effects of HMGB1 on matrix deposition was evaluated in a 3D culture system of human NP cells. These results implicate HMGB1 as a potent DAMP that promotes inflammation in NP cells and degradation of NP tissues. TLR4-HMGB1 axis is a potential major pathway to alleviate disc inflammation and mitigate DD. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Background Evidence on the long-term clinical benefits of individual members of angiotensin II receptor blockers is limited given the lack of head-to-head studies. We conducted a network meta-analysis to determine the comparative efficacy of different members within this drug class with respect to outcomes of (i) blood pressure reduction (at 24 and 52 weeks) and (ii) prevention of cardiovascular disease (>104 weeks). Methods A systematic literature review was conducted – Protocol registration: (PROSPERO – CRD42014007067) – to identify relevant literature from the following databases: Cochrane Library, PubMed, MEDLINE and Embase; searched from inception to July 2016. Randomised controlled trials (RCTs) were included if they reported long-term effectiveness relating to blood pressure, mortality, myocardial infarction or stroke. Eligible studies included those with placebo or specific active-treatment comparators (either another angiotensin II receptor blockers or hydrochlorothiazide). A Bayesian random-effects network model was used to combine direct within-trial comparisons between treatment groups with indirect evidence from other trials. Results Thirty-six studies were identified, representing 28 unique trials. Blood pressure reduction, based on 12 studies (n=807) with fixed dosing regimen, was found to be similar amongst members of the angiotensin receptor blocker drug class at both 24 and 52 weeks. A network meta-analysis of five studies (n=16,716) with a treat-to-target approach found that prevention of all-cause mortality, stroke and myocardial infarction was similar across the angiotensin-receptor blockers therapies initiated. Conclusions Current evidence is insufficient to show differences in any members within the angiotensin II receptor blocker drug class with respect to blood pressuring lowering effects or a reduction in cardiovascular diseases.

Guowei Li,1–3 Yanling Jin,1 Lawrence Mbuagbaw,1,2 Lisa Dolovich,1,2,4 Jonathan D Adachi,2,5 Mitchell AH Levine,1–3,5 Deborah Cook,1,2,5 Zainab Samaan,1,2 Lehana Thabane1,2 1Department of Health Research Methods, Impact and Evidence, McMaster University, Hamilton, ON, Canada; 2St. Joseph’s Healthcare Hamilton, McMaster University, Hamilton, ON, Canada; 3Centre for Evaluation of Medicines, Programs for Assessment of Technology in Health (PATH) Research Institute, McMaster University, Hamilton, ON, Canada; 4Department of Family Medicine, McMaster University, Hamilton, ON, Canada; 5Department of Medicine, McMaster University, Hamilton, ON, Canada Background: Disseminating research protocols, processes, methods or findings via peer-reviewed publications has substantive merits and benefits to various stakeholders. Purpose: In this article, we share strategies to enhance research publication contents (ie, what to write about) and to facilitate scientific writing (ie, how to write) in health research collaborations. Methods: Empirical experience sharing. Results: To enhance research publication contents, we encourage identifying appropriate opportunities for publications, publishing protocols ahead of results papers, seeking publications related to methodological issues, considering justified secondary analyses, and sharing academic process or experience. To advance writing, we suggest setting up scientific writing as a goal, seeking an appropriate mentorship, making full use of scientific meetings and presentations, taking some necessary formal training in areas such as effective communication and time and stress management, and embracing the iterative process of writing. Conclusion: All the strategies we share are dependent upon each other; and they advocate gradual academic accomplishments through study and training in a “success-breeds-success” way. It is expected that the foregoing shared strategies in this paper, together with other previous guidance articles, can assist one with enhancing research publications, and eventually one’s academic success in health research collaborations. Keywords: research publication, scientific writing, health research collaboration