Surgical and non-surgical interventions for primary and salvage treatment of growth hormone-secreting pituitary adenomas in adults.

BACKGROUND: Growth hormone (GH)-secreting pituitary adenoma is a severe endocrine disease. Surgery is the currently recommended primary therapy for patients with GH-secreting tumours. However, non-surgical therapy (pharmacological therapy and radiation therapy) may be performed as primary therapy or may improve surgical outcomes. OBJECTIVES: To assess the effects of surgical and non-surgical interventions for primary and salvage treatment of GH-secreting pituitary adenomas in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, WHO ICTRP, and ClinicalTrials.gov. The date of the last search of all databases was 1 August 2022. We did not apply any language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of more than 12 weeks' duration, reporting on surgical, pharmacological, radiation, and combination interventions for GH-secreting pituitary adenomas in any healthcare setting. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for relevance, screened for inclusion, completed data extraction, and performed a risk of bias assessment. We assessed studies for overall certainty of the evidence using GRADE. We estimated treatment effects using random-effects meta-analysis. We expressed results as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) for continuous outcomes, or in descriptive format when meta-analysis was not possible. MAIN RESULTS: We included eight RCTs that evaluated 445 adults with GH-secreting pituitary adenomas. Four studies reported that they included participants with macroadenomas, one study included a small number of participants with microadenomas. The remaining studies did not specify tumour subtypes. Studies evaluated surgical therapy alone, pharmacological therapy alone, or combination surgical and pharmacological therapy. Methodological quality varied, with many studies providing insufficient information to compare treatment strategies or accurately judge the risk of bias. We identified two main comparisons, surgery alone versus pharmacological therapy alone, and surgery alone versus pharmacological therapy and surgery combined. Surgical therapy alone versus pharmacological therapy alone Three studies with a total of 164 randomised participants investigated this comparison. Only one study narratively described hyperglycaemia as a disease-related complication. All three studies reported adverse events, yet only one study reported numbers separately for the intervention arms; none of the 11 participants were observed to develop gallbladder stones or sludge on ultrasonography following surgery, while five of 11 participants experienced any biliary problems following pharmacological therapy (RR 0.09, 95% CI 0.01 to 1.47; 1 study, 22 participants; very low-certainty evidence). Health-related quality of life was reported to improve similarly in both intervention arms during follow-up. Surgery alone compared to pharmacological therapy alone may slightly increase the biochemical remission rate from 12 weeks to one year after intervention, but the evidence is very uncertain; 36/78 participants in the surgery-alone group versus 15/66 in the pharmacological therapy group showed biochemical remission. The need for additional surgery or non-surgical therapy for recurrent or persistent disease was described for single study arms only. Surgical therapy alone versus preoperative pharmacological therapy and surgery Five studies with a total of 281 randomised participants provided data for this comparison. Preoperative pharmacological therapy and surgery may have little to no effect on the disease-related complication of a difficult intubation (requiring postponement of surgery) compared to surgery alone, but the evidence is very uncertain (RR 2.00, 95% CI 0.19 to 21.34; 1 study, 98 participants; very low-certainty evidence). Surgery alone may have little to no effect on (transient and persistent) adverse events when compared to preoperative pharmacological therapy and surgery, but again, the evidence is very uncertain (RR 1.23, 95% CI 0.75 to 2.03; 5 studies, 267 participants; very low-certainty evidence). Concerning biochemical remission, surgery alone compared to preoperative pharmacological therapy and surgery may not increase remission rates up until 16 weeks after surgery; 23 of 134 participants in the surgery-alone group versus 51 of 133 in the preoperative pharmacological therapy and surgery group showed biochemical remission. Furthermore, the very low-certainty evidence did not suggest benefit or detriment of preoperative pharmacological therapy and surgery compared to surgery alone for the outcomes 'requiring additional surgery' (RR 0.48, 95% CI 0.05 to 5.06; 1 study, 61 participants; very low-certainty evidence) or 'non-surgical therapy for recurrent or persistent disease' (RR 1.22, 95% CI 0.65 to 2.28; 2 studies, 100 participants; very low-certainty evidence). None of the included studies measured health-related quality of life. None of the eight included studies measured disease recurrence or socioeconomic effects. While three of the eight studies reported no deaths to have occurred, one study mentioned that overall, two participants had died within five years of the start of the study. AUTHORS' CONCLUSIONS: Within the context of GH-secreting pituitary adenomas, patient-relevant outcomes, such as disease-related complications, adverse events and disease recurrence were not, or only sparsely, reported. When reported, we found that surgery may have little or no effect on the outcomes compared to the comparator treatment. The current evidence is limited by the small number of included studies, as well as the unclear risk of bias in most studies. The high uncertainty of evidence significantly limits the applicability of our findings to clinical practice. Detailed reporting on the burden of recurrent disease is an important knowledge gap to be evaluated in future research studies. It is also crucial that future studies in this area are designed to report on outcomes by tumour subtype (that is, macroadenomas versus microadenomas) so that future subgroup analyses can be conducted. More rigorous and larger studies, powered to address these research questions, are required to assess the merits of neoadjuvant pharmacological therapy or first-line pharmacotherapy.

COVID-19 vaccine uptake, conspiracy theories, and health literacy among Black individuals in Canada: Racial discrimination, confidence in health, and COVID-19 stress as mediators.

Factors influencing vaccine uptake in Black individuals remain insufficiently documented. Understanding the role of COVID-19 related stress, conspiracy theories, health literacy, racial discrimination experiences, and confidence in health authorities can inform programs to increase vaccination coverage. We sought to analyze these factors and vaccine uptake among Black individuals in Canada. A representative sample of 2002 Black individuals from Ontario, Quebec, Alberta, Nova Scotia, New Brunswick, British Columbia, and Manitoba, aged 14 years or older completed questionnaires assessing vaccine uptake, health literacy, conspiracy theories, racial discrimination experiences, COVID-19-related stress, and confidence in health authorities. Mediation analyses were conducted to assess (1) the effect of health literacy on COVID-19 vaccination uptake through confidence and need, COVID-19 related traumatic stress, and racial discrimination, and (2) the effect of conspiracy beliefs on COVID-19 vaccination uptake through the same factors. Overall, 69.57% (95% confidence interval, 67.55%-71.59%) of the participants were vaccinated and 83.48% of them received two or more doses. Those aged 55 years and older were less likely to be vaccinated, as well as those residing in British Columbia and Manitoba. Mediation models showed that the association between health literacy and COVID-19 vaccine uptake was mediated by confidence in health authorities (B = 0.02, p < 0.001), COVID-19-related stress (B = -0.02, p < 0.001), and racial discrimination (B = -0.01, p = 0.032), but both direct and total effects were nonsignificant. Lastly, conspiracy beliefs were found to have a partial mediation effect through the same mediators (B = 0.02, p < 0.001, B = -0.02, p < 0.001, B = -0.01, p = 0.011, respectively). These findings highlight the need for targeted interventions to address vaccine hesitancy and inform approaches to improve access to vaccinations among Black communities.

Transparency, openness, and reproducible research practices are frequently underused in health economic evaluations.

OBJECTIVES: To investigate the extent to which articles of economic evaluations of healthcare interventions indexed in MEDLINE incorporate research practices that promote transparency, openness, and reproducibility. STUDY DESIGN AND SETTING: We evaluated a random sample of health economic evaluations indexed in MEDLINE during 2019. We included articles written in English reporting an incremental cost-effectiveness ratio in terms of costs per life years gained, quality-adjusted life years, and/or disability-adjusted life years. Reproducible research practices, openness, and transparency in each article were extracted in duplicate. We explored whether reproducible research practices were associated with self-report use of a guideline. RESULTS: We included 200 studies published in 147 journals. Almost half were published as open access articles (n = 93; 47%). Most studies (n = 150; 75%) were model-based economic evaluations. In 109 (55%) studies, authors self-reported use a guideline (e.g., for study conduct or reporting). Few studies (n = 31; 16%) reported working from a protocol. In 112 (56%) studies, authors reported the data needed to recreate the incremental cost-effectiveness ratio for the base case analysis. This percentage was higher in studies using a guideline than studies not using a guideline (72/109 [66%] with guideline vs. 40/91 [44%] without guideline; risk ratio 1.50, 95% confidence interval 1.15-1.97). Only 10 (5%) studies mentioned access to raw data and analytic code for reanalyses. CONCLUSION: Transparency, openness, and reproducible research practices are frequently underused in health economic evaluations. This study provides baseline data to compare future progress in the field.

From complexity to clarity: how directed acyclic graphs enhance the study design of systematic reviews and meta-analyses.

While frameworks to systematically assess bias in systematic reviews and meta-analyses (SRMAs) and frameworks on causal inference are well established, they are less frequently integrated beyond the data analysis stages. This paper proposes the use of Directed Acyclic Graphs (DAGs) in the design stage of SRMAs. We hypothesize that DAGs created and registered a priori can offer a useful approach to more effective and efficient evidence synthesis. DAGs provide a visual representation of the complex assumed relationships between variables within and beyond individual studies prior to data analysis, facilitating discussion among researchers, guiding data analysis, and may lead to more targeted inclusion criteria or set of data extraction items. We illustrate this argument through both experimental and observational case examples.

The impact of social restrictions on the incidence and microbiology of peritonsillar abscess: a retrospective cohort study.

OBJECTIVES: We aimed to explore the impact of social distancing on the incidence and microbiology of peritonsillar abscess (PTA). METHODS: We performed a cross-sectional analysis of all patients with PTA and their microbiological findings in the 2 years preceding versus the 2 years following the COVID-19 lockdown in Denmark (11 March 2020), who were admitted to the Ear-Nose-Throat Department, Aarhus University Hospital. Age-stratified population data for the catchment area were obtained from Statistics Denmark. RESULTS: The annual incidence rate was significantly higher in the 2-year period before (21.8 cases/100 000 inhabitants) compared with after (14.9 cases/100 000) the lockdown (p < 0.001). The number of cases with growth of Streptococcus pyogenes was significantly higher in the period before (n = 67) compared with after (n = 28) the lockdown (p < 0.001), whereas the number of cases positive for Fusobacterium necrophorum (n = 60 vs. n = 64) and streptococcus anginosus group (SAG) (n = 37 vs. n = 43) were stabile (p 0.79 and p 0.58, respectively). The relative prevalence of S. pyogenes was significantly higher in the period before (67/246 cultures, 27%) compared with after (28/179, 16%) the lockdown (p 0.007). On the contrary, the relative prevalence of F. necrophorum and SAG is significantly lower before (60/246, 24% and 37/246, 15%) compared with after (64/179, 36% and 43/179, 24%) the lockdown (p 0.013 and p 0.023). DISCUSSION: Social distancing had a significant impact on the incidence and microbiology of PTA. Our findings suggest that S. pyogenes-positive PTA is highly related to direct social interaction, and represents a contagious pathogen. By contrast, PTA development caused by F. necrophorum and SAG is unrelated to direct social interaction and may be derived from flora imbalance.

EUFOREA/EPOS2020 statement on the clinical considerations for chronic rhinosinusitis with nasal polyps care.

Following the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) treatment algorithm for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), patients suffering from severe uncontrolled CRSwNP are recommended to receive oral corticosteroids, (revision) sinus surgery, systemic biologicals and/or aspirin treatment after desensitization (ATAD). Given the major differences in indications, outcomes, practical considerations, risks and costs of these key pillars of treatment, there is a growing need to define criteria for each treatment option and list the clinically relevant and major considerations for them. This EUFOREA document therefore provides an expert panel overview of the expected outcomes, specific considerations and (contra)indications of the five major treatment arms of severe uncontrolled CRSwNP: oral corticosteroids, primary and revision sinus surgery, biological treatment and ATAD. This overview of treatment considerations is needed to allow physicians and patients to consider the different options in the context of providing optimal and personalized care for severe uncontrolled CRSwNP. In conclusion, the five major treatment options for severe uncontrolled CRSwNP have intrinsic advantages, specific indications and considerations that are of importance to the patient, the physician and the society. This EUFOREA statement supports the unmet need to define criteria for the indication of every treatment pillar of CRSwNP.

Cost-effectiveness of postoperative imaging surveillance strategies for nonfunctional pituitary adenomas after resection with curative intent.

OBJECTIVE: The aim of this study was to determine an optimal follow-up imaging surveillance strategy in terms of cost-effectiveness after resection of nonfunctioning pituitary adenomas with curative intent. METHODS: An individual-level state-transition microsimulation model was used to simulate costs and outcomes associated with three postoperative imaging strategies over a lifetime time horizon: 1) annual MRI surveillance, 2) tapered MRI surveillance (annual surveillance for 5 years followed by surveillance every 2 years), and 3) personalized surveillance (annual surveillance for 5 years followed by surveillance every 2 years when MRI shows remnant disease/postoperative changes, and surveillance at 7, 10, and 15 years for disease-free MRI). Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually. Model outcomes included lifetime costs (2022 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Under base case assumptions, annual surveillance yielded higher costs and lower health effects (QALYs) compared with the tapered and personalized surveillance strategies (dominated). Personalized surveillance demonstrated an additional 0.1 QALY at additional cost ($1298) compared with tapered surveillance (7.7 QALYs at a cost of $12,862). The ICER was $11,793/QALY. The optimal decision was most sensitive to the probability of postoperative changes on MRI after surgery and MRI cost. Accounting for parameter uncertainty, personalized surveillance had a higher probability of being a cost-effective surveillance option compared with the alternative strategies at 79%. CONCLUSIONS: Using standard cost-effectiveness thresholds in the US ($100,000/QALY), personalized surveillance that accounted for remnant disease or postoperative changes on MRI was cost-effective compared with alternative surveillance strategies.

Longitudinal Patient Outcomes in Chronic Dizziness: A Scoping Review.

BACKGROUND: Chronic dizziness can cause significant functional impairment. Outcome measures used in this patient population have not been examined systematically. Consequently, providers lack consensus on the ideal outcome measures to assess the impact of their interventions. OBJECTIVE AND METHODS: We conducted a scoping review to summarize existing literature on outcomes in chronic dizziness (with a minimum of 6 mo of patient follow-up). Among other details, we extracted and analyzed patient demographics, medical condition(s), and the specific outcome measures of each study. RESULTS: Of 19,426 articles meeting the original search terms, 416 met final exclusion after title/abstract and full-text review. Most studies focused on Ménière's disease (75%) and recurrent benign paroxysmal positional vertigo (21%). The most common outcome measures were hearing (62%) and number of attacks by American Academy of Otolaryngology-Head & Neck Surgery criteria (60%). A minority (35%) looked formally at quality-of-life metrics (Dizziness Handicap Index or other). CONCLUSIONS: Ménière's disease and benign paroxysmal positional vertigo are overrepresented in literature on outcome assessment in chronic dizziness. Objective clinical measures are used more frequently than quality-of-life metrics. Future work is needed to identify the optimal outcome measures that reflect new knowledge about the most common causes of chronic dizziness (including persistent postural-perceptual dizziness and vestibular migraine) and consider what is most important to patients.

Comparison of socio-economic determinants of COVID-19 testing and positivity in Canada: A multi-provincial analysis.

BACKGROUND: The effects of the COVID-19 pandemic have been more pronounced for socially disadvantaged populations. We sought to determine how access to SARS-CoV-2 testing and the likelihood of testing positive for COVID-19 were associated with demographic factors, socioeconomic status (SES) and social determinants of health (SDH) in three Canadian provinces. METHODS: An observational population-based cross-sectional study was conducted for the provinces of Ontario, Manitoba and New Brunswick between March 1, 2020 and April 27, 2021, using provincial health administrative data. After excluding residents of long-term care homes, those without current provincial health insurance and those who were tested for COVID-19 out of province, records from provincial healthcare administrative databases were reviewed for 16,900,661 healthcare users. Data was modelled separately for each province in accordance to a prespecified protocol and follow-up consultations among provincial statisticians and collaborators. We employed univariate and multivariate regression models to examine determinants of testing and test results. RESULTS: After adjustment for other variables, female sex and urban residency were positively associated with testing, while female sex was negatively associated with test positivity. In New Brunswick and Ontario, individuals living in higher income areas were more likely to be tested, whereas in Manitoba higher income was negatively associated with both testing and positivity. High ethnocultural composition was associated with lower testing rates. Both high ethnocultural composition and high situational vulnerability increased the odds of testing positive for SARS-CoV-2. DISCUSSION: We observed that multiple demographic, income and SDH factors were associated with SARS-CoV-2 testing and test positivity. Barriers to healthcare access identified in this study specifically relate to COVID-19 testing but may reflect broader inequities for certain at-risk groups.

Vaccine mistrust among Black individuals in Canada: The major role of health literacy, conspiracy theories, and racial discrimination in the healthcare system.

The COVID-19 pandemic disproportionately affected Black communities in Canada in terms of infection and mortality rates compared to the general population. Despite these facts, Black communities are among those with the highest level of COVID-19 vaccine mistrust (COVID-19 VM). We collected novel data to analyze the sociodemographic characteristics and factors associated with COVID-19 VM among Black communities in Canada. A survey was conducted among a representative sample of 2002 Black individuals (51.66% women) aged 14-94 years (M = 29.34; SD = 10.13) across Canada. Vaccine mistrust was assessed as the dependent variable and conspiracy theories, health literacy, major racial discrimination in healthcare settings, and sociodemographic characteristics of participants were assessed as independent variables. Those with a history of COVID-19 infection had higher COVID-19 VM score (M = 11.92, SD = 3.88) compared to those with no history of infection (M = 11.25, SD = 3.83), t (1999) = -3.85, p < 0.001. Participants who reported having experienced major racial discrimination in healthcare settings were more likely to report COVID-19 VM (M = 11.92, SD = 4.03) than those who were not (M = 11.36, SD = 3.77), t (1999) = -3.05, p = 0.002. Results also showed significant differences for age, education level, income, marital status, provinces, language, employment status, and religion. The final hierarchical linear regression showed that conspiracy beliefs (B = 0.69, p < 0.001) were positively associated with COVID-19 VM, while health literacy (B = -0.05, p = 0.002) was negatively associated with it. The mediated moderation model showed that conspiracy theories completely mediated the association between racial discrimination and vaccine mistrust (B = 1.71, p < 0.001). This association was also completely moderated by the interaction between racial discrimination and health literacy (B = 0.42, p = 0.008), indicating that despite having a high level of health literacy, those who experienced major racial discrimination in health services developed vaccine mistrust. This first study on COVID-19 VM exclusively among Black individuals in Canada provides data that can significantly impact the development of tools, trainings, strategies, and programs to make the health systems free of racism and increase their confidence in vaccination for COVID-19 and other infectious diseases.

Preoperative Evaluation of Thyroid Cancer: A Review of Current Best Practices.

OBJECTIVE: The incidence of thyroid cancer has significantly increased in recent decades. Although most thyroid cancers are small and carry an excellent prognosis, a subset of patients present with advanced thyroid cancer, which is associated with increased rates of morbidity and mortality. The management of thyroid cancer requires a thoughtful individualized approach to optimize oncologic outcomes and minimize morbidity associated with treatment. Because endocrinologists usually play a key role in the initial diagnosis and evaluation of thyroid cancers, a thorough understanding of the critical components of the preoperative evaluation facilitates the development of a timely and comprehensive management plan. The following review outlines considerations in the preoperative evaluation of patients with thyroid cancer. METHODS: A clinical review based on current literature was generated by a multidisciplinary author panel. RESULTS: A review of considerations in the preoperative evaluation of thyroid cancer is provided. The topic areas include initial clinical evaluation, imaging modalities, cytologic evaluation, and the evolving role of mutational testing. Special considerations in the management of advanced thyroid cancer are discussed. CONCLUSION: Thorough and thoughtful preoperative evaluation is critical for formulating an appropriate treatment strategy in the management of thyroid cancer.

Post-operative surveillance for somatotroph, lactotroph and non-functional pituitary adenomas after curative resection: a systematic review.

CONTEXT: Pituitary tumors are the third most common brain tumor and yet there is no standardization of the surveillance schedule and assessment modalities after transsphenoidal surgery. EVIDENCE ACQUISITION: OVID, EMBASE and the Cochrane Library databases were systematically screened from database inception to March 5, 2020. Inclusion and exclusion criteria were designed to capture studies examining detection of pituitary adenoma recurrence in patients 18 years of age and older following surgical resection with curative intent. EVIDENCE SYNTHESIS: A total of 7936 abstracts were screened, with 812 articles reviewed in full text and 77 meeting inclusion criteria for data extraction. A pooled analysis demonstrated recurrence rates at 1 year, 5 years and 10 years for non-functioning pituitary adenomas (NFPA; N = 3533 participants) were 1%, 17%, and 33%, for prolactin-secreting adenomas (PSPA; N = 1295) were 6%, 21%, and 28%, and for growth-hormone pituitary adenomas (GHPA; N = 1257) were 3%, 8% and 13%, respectively. Rates of recurrence prior to 1 year were 0% for NFPA, 1-2% for PSPA and 0% for GHPA. The mean time to disease recurrence for NFPA, PSPA and GHPA were 4.25, 2.52 and 4.18 years, respectively. CONCLUSIONS: This comprehensive review of the literature quantified the recurrence rates for commonly observed pituitary adenomas after transsphenoidal surgical resection with curative intent. Our findings suggest that surveillance within 1 year may be of low yield. Further clinical trials and cohort studies investigating cost-effectiveness of surveillance schedules and impact on quality of life of patients under surveillance will provide further insight to optimize follow-up.

Prevalence and factors related to COVID-19 vaccine hesitancy and unwillingness in Canada: A systematic review and meta-analysis.

This systematic review and meta-analysis examined the prevalence and factors associated with vaccine hesitancy and vaccine unwillingness in Canada. Eleven databases were searched in March 2022. The pooled prevalence of coronavirus disease 2019 (COVID-19) vaccine hesitancy and unwillingness was estimated. Subgroup analyses and meta-regressions were performed. Out of 667 studies screened, 86 full-text articles were reviewed, and 30 were included in the systematic review. Twenty-four articles were included in the meta-analysis; 12 for the pooled prevalence of vaccine hesitancy (42.3% [95% CI, 33.7%-51.0%]) and 12 for vaccine unwillingness (20.1% [95% CI, 15.2%-24.9%]). Vaccine hesitancy was higher in females (18.3% [95% CI, 12.4%-24.2%]) than males (13.9% [95% CI, 9.0%-18.8%]), and in rural (16.3% [95% CI, 12.9%-19.7%]) versus urban areas (14.1% [95%CI, 9.9%-18.3%]). Vaccine unwillingness was higher in females (19.9% [95% CI, 11.0%-24.8%]) compared with males (13.6% [95% CI, 8.0%-19.2%]), non-White individuals (21.7% [95% CI, 16.2%-27.3%]) than White individuals (14.8% [95% CI, 11.0%-18.5%]), and secondary or less (24.2% [95% CI, 18.8%-29.6%]) versus postsecondary education (15.9% [95% CI, 11.6%-20.2%]). Factors related to racial disparities, gender, education level, and age are discussed.

A Systematic Review on Vaccine Hesitancy in Black Communities in Canada: Critical Issues and Research Failures.

Black communities have been disproportionately impacted by Coronavirus Disease 2019 (COVID-19) in Canada, in terms of both number of infections and mortality rates. Yet, according to early studies, vaccine hesitancy appears to be higher in Black communities. The purpose of this systematic review is to examine the prevalence and factors associated with vaccine hesitancy in Black communities in Canada. Peer-reviewed studies published from 11 March 2020 to 26 July 2022, were searched through eleven databases: APA PsycInfo (Ovid), Cairn.info, Canadian Business & Current Affairs (ProQuest), CPI.Q (Gale OneFile), Cochrane CENTRAL (Ovid), Embase (Ovid), Érudit, Global Health (EBSCOhost), MEDLINE (Ovid), and Web of Science (Clarivate). Eligible studies were published in French or English and had empirical data on the prevalence or factors associated with vaccine hesitancy in samples or subsamples of Black people. Only five studies contained empirical data on vaccine hesitancy in Black individuals and were eligible for inclusion in this systematic review. Black individuals represented 1.18% (n = 247) of all included study samples (n = 20,919). Two of the five studies found that Black individuals were more hesitant to be vaccinated against COVID-19 compared to White individuals, whereas the other three found no significant differences. The studies failed to provide any evidence of factors associated with vaccine hesitancy in Black communities. Despite national concerns about vaccine hesitancy in Black communities, a color-blind approach is still predominant in Canadian health research. Of about 40 studies containing empirical data on vaccine hesitancy in Canada, only five contained data on Black communities. None analyzed factors associated with vaccine hesitancy in Black communities. Policies and strategies to strengthen health research in Black communities and eliminate the color-blind approach are discussed.

Salivary testing for SARS-CoV-2 in the pediatric population: a diagnostic accuracy study.

BACKGROUND: Accurate and timely testing for SARS-CoV-2 in the pediatric population is crucial to control the COVID-19 pandemic; saliva testing has been proposed as a less invasive alternative to nasopharyngeal swabs. We sought to compare the detection of SARS-CoV-2 using saliva versus nasopharyngeal swab in the pediatric population, and to determine the optimum time of testing for SARS-CoV-2 using saliva. METHODS: We conducted a longitudinal diagnostic study in Ottawa, Canada, from Jan. 19 to Mar. 26, 2021. Children aged 3-17 years were eligible if they exhibited symptoms of COVID-19, had been identified as a high-risk or close contact to someone confirmed positive for SARS-CoV-2 or had travelled outside Canada in the previous 14 days. Participants provided both nasopharyngeal swab and saliva samples. Saliva was collected using a self-collection kit (DNA Genotek, OM-505) or a sponge-based kit (DNA Genotek, ORE-100) if they could not provide a saliva sample into a tube. RESULTS: Among 1580 paired nasopharyngeal and saliva tests, 60 paired samples were positive for SARS-CoV-2. Forty-four (73.3%) were concordant-positive results and 16 (26.6%) were discordant, among which 8 were positive only on nasopharyngeal swab and 8 were positive only on saliva testing. The sensitivity of saliva was 84.6% (95% confidence interval 71.9%-93.1%). INTERPRETATION: Salivary testing for SARS-CoV-2 in the pediatric population is less invasive and shows similar detection of SARS-CoV-2 to nasopharyngeal swabs. It may therefore provide a feasible alternative for diagnosis of SARS-CoV-2 infection in children.

Cost-effectiveness of direct surgery versus preoperative octreotide therapy for growth-hormone secreting pituitary adenomas.

PURPOSE: The objective of this study was to compare the cost-effectiveness of preoperative octreotide therapy followed by surgery versus the standard treatment modality for growth-hormone secreting pituitary adenomas, direct surgery (that is, surgery without preoperative treatment) from a public third-party payer perspective. METHODS: We developed an individual-level state-transition microsimulation model to simulate costs and outcomes associated with preoperative octreotide therapy followed by surgery and direct surgery for patients with growth-hormone secreting pituitary adenomas. Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs [2020 United States (US) Dollars], quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: Under base case assumptions, direct surgery was found to be the dominant strategy as it yielded lower costs and greater health effects (QALYs) compared to preoperative octreotide strategy in the second-order Monte Carlo microsimulation. The ICER was most sensitive to probability of remission following primary therapy and duration of preoperative octreotide therapy. Accounting for joint parameter uncertainty, direct surgery had a higher probability of demonstrating a cost-effective profile compared to preoperative octreotide treatment at 77% compared to 23%, respectively. CONCLUSIONS: Using standard benchmarks for cost-effectiveness in the US ($100,000/QALY), preoperative octreotide therapy followed by surgery may not be cost-effective compared to direct surgery for patients with growth-hormone secreting pituitary adenomas but the result is highly sensitive to initial treatment failure and duration of preoperative treatment.

Evaluating the Rising Incidence of Thyroid Cancer and Thyroid Nodule Detection Modes: A Multinational, Multi-institutional Analysis.

Importance: There is epidemiologic evidence that the increasing incidence of thyroid cancer is associated with subclinical disease detection. Evidence for a true increase in thyroid cancer incidence has also been identified. However, a true increase in disease would likely be heralded by an increased incidence of thyroid-referable symptoms in patients presenting with disease. Objectives: To evaluate whether modes of detection (MODs) used to identify thyroid nodules for surgical removal have changed compared with historic data and to determine if MODs vary by geographic location. Design, Setting, and Participants: This was a retrospective analysis of pathology and medical records of 1328 patients who underwent thyroid-directed surgery in 16 centers in 4 countries: 4 centers in Canada, 1 in Denmark, 1 in South Africa, and 12 in the US. The participants were the first 100 patients (or the largest number available) at each center who had thyroid surgery in 2019. The MOD of the thyroid finding that required surgery was classified using an updated version of a previously validated tool as endocrine condition, symptomatic thyroid, surveillance, or without thyroid-referable symptoms (asymptomatic). If asymptomatic, the MOD was further classified as clinician screening examination, patient-requested screening, radiologic serendipity, or diagnostic cascade. Main Outcomes and Measures: The MOD of thyroid nodules that were surgically removed, by geographic variation; and the proportion and size of thyroid cancers discovered in patients without thyroid-referable symptoms compared with symptomatic detection. Data analyses were performed from April 2021 to February 2022. Results: Of the 1328 patients (mean [SD] age, 52 [15] years; 993 [75%] women; race/ethnicity data were not collected) who underwent thyroid surgery that met inclusion criteria, 34% (448) of the surgeries were for patients with thyroid-related symptoms, 41% (542) for thyroid findings discovered without thyroid-referable symptoms, 14% (184) for endocrine conditions, and 12% (154) for nodules with original MOD unknown (under surveillance). Cancer was detected in 613 (46%) patients; of these, 30% (183 patients) were symptomatic and 51% (310 patients) had no thyroid-referable symptoms. The mean (SD) size of the cancers identified in the symptomatic group was 3.2 (2.1) cm (median [range] cm, 2.6 [0.2-10.5]; 95% CI, 2.91-3.52) and in the asymptomatic group, 2.1 (1.4) cm (median [range] cm, 1.7 [0.05-8.8]; 95% CI, 1.92-2.23). The MOD patterns were significantly different among all participating countries. Conclusions and Relevance: This retrospective analysis found that most thyroid cancers were discovered in patients who had no thyroid-referable symptoms; on average, these cancers were smaller than symptomatic thyroid cancers. Still, some asymptomatic cancers were large, consistent with historic data. The substantial difference in MOD patterns among the 4 countries suggests extensive variations in practice.

Recovery of Cranial Nerve Deficits in Patients Presenting with Pituitary Apoplexy: A Case Series.

Background Pituitary apoplexy (PA) is a rare complication of pituitary tumors that can present with a myriad of symptoms, including sudden onset cranial nerve deficits. After patient stabilization and hormone replacement, surgical decompression is often recommended. The timing of surgical decompression remains controversial. In this case series, we describe our institutional experience pertaining to the cranial nerve recovery in patients who underwent endoscopic endonasal transsphenoidal (EETS) surgery for PA while evaluating outcome based on tumor stage using the suprasellar infrasellar parasellar anterior posterior (SIPAP) classification. Design Present study is a single-institution retrospective cohort. Methods A retrospective review of all EETS cases for pituitary tumor resection between November 2009 and August 2018. Queries of the hospital database were completed by trained personnel to identify cases of PA treated using the EETS approach. Baseline characteristics, tumor type, endocrine data, and SIPAP classification based on preoperative magnetic resonance imaging (MRI) and operation characteristics were extracted from medical records. Postoperative results were extracted for the duration of the follow-up period available for each patient. Results Fifteen cases of PA were identified. Patient follow-up period was a mean of 30 months. The cranial nerve deficits present at admission were visual deficit (33%); unilateral third nerve palsy (47%) and unilateral sixth nerve palsy (27%). No fourth nerve palsies were observed. Following EETS, 60% of patients with preoperative visual deficit had normal visual fields. For those with third and sixth nerve palsies preoperatively, 43 and 75%, respectively, had return to normal function postoperatively. SIPAP tumor characteristics were not related to postoperative cranial nerve recovery. Conclusion In this series of surgically treated patients with pituitary apoplexy, all cranial nerve deficits normalized or improved following surgery. The tumor SIPAP classification was not associated with patient outcome. Though in a small series, the presented results suggest surgical treatment is beneficial for these patients.

Vitamin D Supplementation for Benign Paroxysmal Positional Vertigo: A Systematic Review.

OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is commonly attributed to displaced otoconia. These have been shown to have biomineralization close to that of bone, and vitamin D deficiency has been associated with BPPV. We aim to systematically review the available literature on vitamin D supplementation and BPPV intensity and recurrence in adults. DATABASES REVIEWED: PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Current Controlled Trials, and ClinicalTrials.gov. METHODS: We systematically reviewed the available literature from 1947 to April 2020. The study protocol was registered in the PROSPERO database (trial registration: CRD42020183195). RESULTS: A total of 179 abstracts were identified and screened by two independent reviewers. Based on inclusion and exclusion criteria, six studies were selected and subjected to a quality assessment. In one randomized clinical trial (RCT), vitamin D supplementation was found to reduce annual recurrence rate of vertigo in patient with BPPV and subnormal serum vitamin D levels compared with placebo (odds ratio, 0.69; 95% confidence interval, 0.54-0.90). Non-RCTs demonstrated the possibility of a null effect in the random effects model (odds ratio, 0.08; 95% confidence interval, 0.00-1.56). The RCT considered as low risk of bias. All of the nonrandomized studies were assessed as serious risk of bias. CONCLUSIONS: The intervention studies identified consistently demonstrated a decrease in BPPV recurrence with supplementation of vitamin D in patients with subnormal vitamin D levels. Although there is a paucity of high-quality studies, the present literature does highlight a role for optimization of vitamin D levels in patients with BPPV.