The INMSG Survey on the Loss of Signal Management on the First Side During Planned Bilateral Thyroid Surgery.

BACKGROUND: The aim of this study is to describe the management and associated follow-up strategies adopted by thyroid surgeons with different surgical volumes when loss of signal (LOS) occurred on the first side of planned bilateral thyroid surgery, and to further define the consensus on intraoperative neuromonitoring (IONM) applications. METHODS: The International Neural Monitoring Study Group (INMSG) web-based survey was sent to 950 thyroid surgeons worldwide. The survey included information on the participants, IONM team/equipment/procedure, intraoperative/postoperative management of LOS, and management of LOS on the first side of thyroidectomy for benign and malignant disease. RESULTS: Out of 950, 318 (33.5%) respondents completed the survey. Subgroup analyses were performed based on thyroid surgery volume: <50 cases/year (n = 108, 34%); 50 to 100 cases/year (n = 69, 22%); and >100 cases/year (n = 141, 44.3%). High-volume surgeons were significantly (P < .05) more likely to perform the standard procedures (L1-V1-R1-S1-S2-R2-V2-L2), to differentiate true/false LOS, and to verify the LOS lesion/injury type. When LOS occurs, most surgeons arrange otolaryngologists or speech consultation. When first-side LOS occurs, not all respondents decided to perform stage contralateral surgery, especially for malignant patients with severe disease (eg, extrathyroid invasion and poorly differentiated thyroid cancer). CONCLUSIONS: Respondents felt that IONM was optimized when conducted under a collaborative team-based approach, and completed IONM standard procedures and management algorithm for LOS, especially those with high volume. In cases of first-site LOS, surgeons can determine the optimal management of disease-related, patient-related, and surgical factors. Surgeons need additional education on LOS management standards and guidelines to master their decision-making process involving the application of IONM.

Latent profiles of modifiable dementia risk factors in later midlife: relationships with incident dementia, cognition, and neuroimaging outcomes.

In 2020, the Lancet Commission identified 12 modifiable factors that increase population-level dementia risk. It is unclear if these risk factors co-occur among individuals in a clinically meaningful way. Using latent class analysis, we identified profiles of modifiable dementia risk factors in dementia-free adults aged 60-64 years from the UK Biobank. We then estimated associations between these profiles with incident dementia, cognition, and neuroimaging outcomes, and explored the differences across profiles in the effects of a polygenic risk score for Alzheimer's disease on outcomes. In 55,333 males and 63,063 females, three sex-specific latent profiles were identified: cardiometabolic risk, substance use-related risk, and low risk. The cardiometabolic risk profile in both males and females was associated with greater incidence of all-cause dementia (male: OR [95% CI] = 2.33 [2.03, 2.66]; female: OR [95% CI] = 1.44 [1.24, 1.68]), poorer cognitive performance, greater brain atrophy, and greater white matter hyperintensity volume compared to the low risk profile. The substance use-related risk profile in males was associated with poorer cognitive performance and greater white matter hyperintensities compared to the low risk profile, but no difference in all-cause dementia incidence was observed (OR [95% CI] = 1.00 [0.95, 1.06]). In females, the substance use-related risk profile demonstrated increased dementia incidence (OR [95% CI] = 1.58 [1.57, 1.58]) and greater brain atrophy but smaller white matter hyperintensity volume compared to the low risk profile. The polygenic risk score had larger effects among females, and differentially influenced outcomes across profiles; for instance, there were larger effects of the polygenic risk score on atrophy in the cardiometabolic profile vs. the low risk profile among males, and larger effects of the polygenic risk score on loss of white matter integrity in the cardiometabolic profile vs. the low risk profile among females. These results reveal three modifiable dementia risk profiles, their unique cognitive/neuroimaging outcomes, and their interactions with genetic risk for Alzheimer's disease. These differences highlight the need to consider population heterogeneity in risk prediction tools and in planning personalized prevention strategies.

Phosphodiesterase-5 Inhibitors and Dementia Risk: Confounding by Indication in Real-World Studies.

Pharmacoepidemiologic studies using routinely collected data allow researchers to propose drugs for repurposing trials for dementia prevention or treatment. A recent cohort study reported a 54% lower dementia risk among users of sildenafil compared to users of certain cardiovascular medications. We caution that "confounding by indication" can arise when outcomes are compared between a drug of interest and an inappropriate comparator. Here, we emphasize important considerations in selecting an active comparator. We assess the implications of substantial risk of confounding by indication in pharmacoepidemiologic studies linking phosphodiesterase-5 inhibitors to lower dementia risk.

Longitudinal relationships between depressive symptoms, functional impairment, and physical activity in later late life.

The purpose of this study was to investigate relationships between depressive symptoms, functional disability, and physical activity over time in community-dwelling older adults. The Religious Order Study and Rush Memory and Aging Project are longitudinal cohort studies based in the United States which began recruitment in 1994 and 1997, respectively. This analysis included 1611 participants (27.4% male, 92.9% White, 74.7% cognitively normal) who were included at age 80 and followed until age 90. Depressive symptoms were assessed using the modified Center for Epidemiologic Studies Depression scale. Functional disability was assessed using the Instrumental Activities of Daily Living (IADL) scale. Physical activity was self-reported hours of weekly exercise. Reciprocal temporal relationships between these variables were investigated using a random intercept cross-lagged panel model, which decomposes observed variables into stable between-person ('trait') and variable within-person ('state') components to estimate the directional effects between variables over time. Traits for depressive symptoms, IADL disability, and physical activity were correlated. IADL disability showed autoregressive effects; disability starting at age 82 strongly predicted subsequent disability. Consistent autoregressive effects were not observed for depressive symptoms nor physical activity. Several small cross-lagged effects between states were observed for IADL disability and physical activity, as well as for IADL disability and depressive symptoms. There were no direct effects between depressive symptoms and physical activity, but several paths through IADL disability were observed between ages 82 and 88. Functional disability played an important role in octogenarians, highlighting the importance of maintaining functional independence later in life.

Real-time surgical simulation training for recurrent laryngeal nerve and facial nerve dissection.

BACKGROUND: Head and neck surgical simulation training (SST) is an important part in otolaryngology head and neck surgical education. In this study, we provide a live porcine model for SST in recurrent laryngeal nerve (RLN) and facial nerve (FN) dissection for otolaryngology head and neck residents. METHODS: A lecture with surgical manual is provided to illustrate the surgical landmarks of pig, and step-by-step procedures for thyroid and parotid surgery, as well as neck dissection. We used 4-month-old pig weighting 32 kg for the SST. The mentor demonstrated result of RLN injury with continuous nerve monitoring. Participants used monopolar stimulation probe (4 pulse/s, 100 µs, 3-8 mA; Medtronic) to identify and intermittent monitor the RLN and FN during the SST. After the dissection course, we conducted a questionnaire survey to check the effectiveness of this training model. RESULTS: Total 30 participants were recruited, including 16 female and 14 male resident doctors. There were 1, 4 and 25 learners for 3rd year, 4th and 5th years residents, respectively. Before this training course, 53 % (16/30) and 63 % (19/30) had successful experience in finding the RLN and FN, respectively. After the SST, all of our participants had successful identify the RLN and FN (p-value <0.01); all had positive response to stimulation and familiar with the procedure. CONCLUSIONS: The live porcine model is effectiveness in SST for RLN and FN dissection. Live porcine model with real-time RLN and FN monitoring should be provided for otolaryngology head and neck resident training.

Insights into the molecular mechanism of ParABS system in chromosome partition by HpParA and HpParB.

The ParABS system, composed of ParA (an ATPase), ParB (a DNA binding protein), and parS (a centromere-like DNA), regulates bacterial chromosome partition. The ParB-parS partition complex interacts with the nucleoid-bound ParA to form the nucleoid-adaptor complex (NAC). In Helicobacter pylori, ParA and ParB homologs are encoded as HpSoj and HpSpo0J (HpParA and HpParB), respectively. We determined the crystal structures of the ATP hydrolysis deficient mutant, HpParAD41A, and the HpParAD41A-DNA complex. We assayed the CTPase activity of HpParB and identified two potential DNA binding modes of HpParB regulated by CTP, one is the specific DNA binding by the DNA binding domain and the other is the non-specific DNA binding through the C-terminal domain under the regulation of CTP. We observed an interaction between HpParAD41A and the N-terminus fragment of HpParB (residue 1-10, HpParBN10) and determined the crystal structure of the ternary complex, HpParAD41A-DNA-HpParBN10 complex which mimics the NAC formation. HpParBN10 binds near the HpParAD41A dimer interface and is clamped by flexible loops, L23 and L34, through a specific cation-π interaction between Arg9 of HpParBN10 and Phe52 of HpParAD41A. We propose a molecular mechanism model of the ParABS system providing insight into chromosome partition in bacteria.

Transcriptional, post-transcriptional, and post-translational regulation of polyunsaturated fatty acid synthase genes in Aurantiochytrium limacinum strain BL10: Responses to nitrogen starvation.

Under nitrogen deficient conditions, the Aurantiochytrium limacinum strain BL10 greatly increases the production of docosahexaenoic acid (DHA) and n-6 docosapentaenoic acid. Researchers have yet to elucidate the mechanism by which BL10 promotes the activity of polyunsaturated fatty acid synthase (Pfa), which plays a key role in the synthesis of polyunsaturated fatty acid (PUFA). Analysis in the current study revealed that in nitrogen-depleted environments, BL10 boosts the transcription and synthesis of proteins by facilitating the expression of pfa genes via transcriptional regulation. It was also determined that BL10 adjusts the lengths of the 5'- and 3'-untranslated regions (suggesting post-transcriptional regulation) and modifies the ratio of two Pfa1 isoforms to favor PUFA production via post-translational regulation (ubiquitination). These findings clarify the exceptional DHA production of BL10 and provide additional insights into the regulatory mechanisms of PUFA biosynthesis in Aurantiochytrium.

Intraoperative neuromonitoring during thyroidectomy does not decrease vocal cord palsy risk, but the cumulative experience of the surgeon may.

PURPOSE: To evaluate the influence of intraoperative neuromonitoring (IONM) on vocal cord palsy (VCP) rates and assess the temporal trends in VCP rates. METHODS: The subjects of this retrospective study were patients who underwent thyroidectomy for thyroid cancer between March, 2014 and June, 2022, at a university hospital in Korea. We compared VCP rates between the non-IONM and IONM groups and analyzed the risk factors for VCP and VCP rates over time. RESULTS: A total of 712 patients were included in the analysis. The rates of transient and permanent VCP did not differ significantly between the non-IONM and IONM groups. Transient VCP occurred in 4.6% and 4.3% patients (p = 0.878) and VCP was permanent in 0.7% and 0.4% patients (p = 0.607) in the non-IONM and IONM groups, respectively. Among the nerves at risk, transient damage occurred in 2.8% and 3.0% patients (p = 0.901), and permanent damage occurred in 0.4% and 0.3% (p = 0.688), respectively. Multivariate analysis revealed no significant risk factors for VCP. There was a significant decreasing trend in VCP rates over time as the cumulative number of cases increased (p = 0.017). CONCLUSIONS: IONM did not reduce the risk of VCP significantly. However, the declining trend of VCP rates suggests that the surgeon's experience may mitigate VCP risk.

Bacterial Colonization on Endoscopic Materials and Surgical Field Without Infections After Transoral Endoscopic Thyroidectomy.

INTRODUCTION: Our aim was to determine whether bacteria contamination occurred within the surgical field or on endoscopic equipment during surgery using the transoral endoscopic thyroidectomy vestibular approach (TOETVA). MATERIALS AND METHODS: Participants were recruited from patients planned for TOETVA between May 2017 and December 2019. Bacterial samples were taken before and at the conclusion of the TOETVA procedure. The preoperative and postoperative samples were taken from the endoscopic materials and inferior oral vestibulum using a sterile flocked swab. RESULTS: The study resulted in 480 samples (80 TOETVAs). No vestibular, port site, or neck infections occurred in any of the patients. Three (3.7%) out of 80 patients developed postoperative fever. Our results show different microbial communities during TOETVA. The most prevalent species detected were S treptococcus species. Multivariate logistic regression analyses revealed that the degree of contamination depended on the sampling site (inferior vestibulum > equipment) ( P =0.03). In addition, the abundance of bacteria was affected by operative time ( P =0.013). There were no significant differences observed in isolation frequencies of bacteria in malignancy ( P =0.34). CONCLUSIONS: TOETVA surgery is categorized as a "clean-contaminated" operation. A swab identified the common colonizers of oral microbiota on the endoscopic equipment and within the surgical field.

Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging.

BACKGROUND AND OBJECTIVES: Mounting evidence supports sex differences in Alzheimer disease (AD) risk. Vascular and hormonal factors may together contribute to AD risk in female adults. We investigated whether age at menopause, vascular risk, and history of hormone therapy (HT) containing estrogens together influence cognition over a 3-year follow-up period. We hypothesized that earlier menopause and elevated vascular risk would have a synergistic association with lower cognitive scores at follow-up and that HT containing estrogens would attenuate this synergistic association to preserve cognition. METHODS: We used data from postmenopausal female participants and age-matched male participants in the Canadian Longitudinal Study on Aging. Vascular risk was calculated using a summary score of elevated blood pressure, antihypertensive medications, elevated low-density lipoprotein cholesterol, diabetes, smoking, and obesity. Cognition was measured with a global cognitive composite at baseline and 3-year follow-up. Linear models tested independent and interactive associations of age at menopause, vascular risk, and HT history with cognition at 3-year follow-up, adjusting for baseline cognition, baseline age, years of education, and test language (English/French). RESULTS: We included 8,360 postmenopausal female participants (mean age at baseline = 65.0 ± 8.53 years, mean age at menopause = 50.1 ± 4.62 years) and 8,360 age-matched male participants for comparison. There was an interaction between age at menopause and vascular risk, such that earlier menopause and higher vascular risk were synergistically associated with lower cognitive scores at follow-up (ß = 0.013, 95% CI 0.001-0.025, p = 0.03). In stratified analyses, vascular risk was associated with lower cognitive scores in female participants with earlier menopause (menopausal ages 35-48 years; ß = -0.044, 95% CI -0.066 to -0.022, p < 0.001), but not average (ages 49-52 years; ß = -0.007, 95% CI -0.027 to 0.012, p = 0.46) or later menopause (ages 53-65 years; ß = 0.003, 95% CI -0.020 to 0.025, p = 0.82). The negative association of vascular risk with cognition in female participants with earlier menopause was stronger than the equivalent association in age-matched male participants. HT history did not further modify the synergistic association of age at menopause and vascular risk with follow-up cognition (ß = -0.005, 95% CI -0.032 to 0.021, p = 0.69). DISCUSSION: Endocrine and vascular processes may synergistically contribute to increased risk of cognitive decline in female adults. These findings have implications for the development of sex-specific dementia prevention strategies.

Evaluation of a National Radiation Oncology Research and Mentorship Program.

PURPOSE: The Canadian Association of Radiation Oncology Annual Scientific Meeting Medical Student Research and Mentorship Award was established in 2020 to support medical students pursuing radiation oncology (RO) research and RO as a career. This study is an evaluation of the effect of this national research and mentorship award on medical students, resident mentors, and research supervisors over 3 iterations. METHODS AND MATERIALS: Three separate surveys were created for medical student mentees, RO resident mentors, and attending research supervisors. These surveys were developed using best practice strategies for medical education surveys and circulated for peer review among experts in oncology medical education. The surveys were sent to the 52 individuals (18 students, 18 residents, 16 supervisors) who participated in 3 cycles of Canadian Association of Radiation Oncology ASM MSRMA (2020-21, 2021-22, 2022-23). After anonymization, quantitative answers were analyzed using descriptive statistics, and narrative responses were evaluated using a grounded theory approach. RESULTS: There was a 90% survey response rate. For medical student mentees, the award maintained (71%) or increased (24%) interest in pursuing an RO career. Students reported receiving helpful tips for residency applications and insight into RO residency, research, and career planning advice. Only the first student cohort currently has matching results for residency, with approximately 50% matching to RO. All resident mentor respondents felt the program either maintained or increased motivation to mentor students in RO. Research project supervisors unanimously enjoyed their role in this program and would recommend and participate in this program again. CONCLUSIONS: A national research and mentorship award for medical students has shown a positive effect on participants. Medical students felt this award program motivated them to continue pursuing oncology research and a potential career in RO. The program also enhanced mentorship skills in residents and research supervisors, which encourages further RO mentorship, teaching, and exposure for future generations of students.

Prognostic nutritional index as a predictive marker for acute kidney injury in adult critical illness population: a systematic review and diagnostic test accuracy meta-analysis.

BACKGROUND: The prognostic nutritional index (PNI), integrating nutrition and inflammation markers, has been increasingly recognized as a prognostic predictor in diverse patient cohorts. Recently, its effectiveness as a predictive marker for acute kidney injury (AKI) in various clinical settings has gained attention. This study aims to assess the predictive accuracy of the PNI for AKI in critically ill populations through systematic review and meta-analysis. METHODS: A systematic review was conducted using the databases MEDLINE, EMBASE, PubMed, and China National Knowledge Infrastructure up to August 2023. The included trials reported the PNI assessment in adult population with critical illness and its predictive capacity for AKI. Data on study characteristics, subgroup covariates, and diagnostic performance of PNI, including sensitivity, specificity, and event rates, were extracted. A diagnostic test accuracy meta-analysis was performed. Subgroup analyses and meta-regression were utilized to investigate the sources of heterogeneity. The GRADE framework evaluated the confidence in the meta-analysis's evidence. RESULTS: The analysis encompassed 16 studies with 17 separate cohorts, totaling 21,239 patients. The pooled sensitivity and specificity of PNI for AKI prediction were 0.67 (95% CI 0.58-0.74) and 0.74 (95% CI 0.67-0.80), respectively. The pooled positive likelihood ratio was 2.49 (95% CI 1.99-3.11; low certainty), and the negative likelihood ratio was 0.46 (95% CI 0.37-0.56; low certainty). The pooled diagnostic odds ratio was 5.54 (95% CI 3.80-8.07), with an area under curve of summary receiver operating characteristics of 0.76. Subgroup analysis showed that PNI's sensitivity was higher in medical populations than in surgical populations (0.72 vs. 0.55; p < 0.05) and in studies excluding patients with chronic kidney disease (CKD) than in those including them (0.75 vs. 0.56; p < 0.01). Overall, diagnostic performance was superior in the non-chronic kidney disease group. CONCLUSION: Our study demonstrated that PNI has practical accuracy for predicting the development of AKI in critically ill populations, with superior diagnostic performance observed in medical and non-CKD populations. However, the diagnostic efficacy of the PNI has significant heterogeneity with different cutoff value, indicating the need for further research.

Correction: A Novel Convolutional Neural Network for the Diagnosis and Classification of Rosacea: Usability Study.

[This corrects the article DOI: 10.2196/23415.].

Importance of age at 2nd implantation and interimplant interval to the outcome of bilateral prelingually deafened pediatric cochlear implantation.

BACKGROUND: In Taiwan, the number of cases of sequential bilateral pediatric cochlear implantation (CI) is increasing but data regarding its effectiveness and impact of the reimbursement policy are lacking. We examined the speech perception and quality of life (QOL) of bilateral prelingually deaf children who underwent sequential CI, considering the effects of age at the time of second implantation and interimplant interval. METHODS: We enrolled 124 Mandarin-speaking participants who underwent initial cochlear implant (CI1) in 2001-2019 and a second CI (CI2) in 2015-2020. Patients were followed up for ≥2 years and were categorized into groups based on age at the time of CI2 implantation (<3.5, 3.6-7, 7.1-10, 10.1-13, and 13.1-18 years) and interimplant interval (0.5-3, 3.1-5, 5.1-7, 7.1-10, and >10 years). We evaluated speech perception, device usage rates, and QOL using subjective questionnaires (Speech, Spatial, and Qualities of Hearing and Comprehension Cochlear Implant Questionnaire). RESULTS: Speech perception scores of CI2 were negatively correlated with ages at the time of CI1 and CI2 implantation and interimplant interval. Older age and a longer interimplant interval were associated with higher nonuse rates for CI2 and worse auditory performance and QOL. Among individuals aged >13 years with interimplant intervals >10 years, up to 44% did not use their second ear. Patients aged 7.1 to 10 years had better speech perception and higher questionnaire scores than those aged 10.1 to 13 and 13.1 to 18 years. Furthermore, patients aged 10.1 to 13 years had a lower rate of continuous CI2 usage compared to those aged 7.1 to 10 years. CONCLUSION: Timely implantation of CI2 is essential to achieve optimal outcomes, particularly among sequentially implanted patients with long-term deafness in the second ear and no improvement with hearing aids following CI1 implantation. For CI2 implantation, an upper limit of age of 10 years and interimplant interval of 7 years are essential to prevent suboptimal outcomes. These data can provide useful information to implant recipients, their families, and medical and audiological professionals, enabling a comprehensive understanding of the benefits and potential impacts of the timing of CI2 implantation.

Two-stage deep-learning-based colonoscopy polyp detection incorporating fisheye and reflection correction.

BACKGROUND AND AIM: Colonoscopy is a useful method for the diagnosis and management of colorectal diseases. Many computer-aided systems have been developed to assist clinicians in detecting colorectal lesions by analyzing colonoscopy images. However, fisheye-lens distortion and light reflection in colonoscopy images can substantially affect the clarity of these images and their utility in detecting polyps. This study proposed a two-stage deep-learning model to correct distortion and reflections in colonoscopy images and thus facilitate polyp detection. METHODS: Images were collected from the PolypSet dataset, the Kvasir-SEG dataset, and one medical center's patient archiving and communication system. The training, validation, and testing datasets comprised 808, 202, and 1100 images, respectively. The first stage involved the correction of fisheye-related distortion in colonoscopy images and polyp detection, which was performed using a convolutional neural network. The second stage involved the use of generative and adversarial networks for correcting reflective colonoscopy images before the convolutional neural network was used for polyp detection. RESULTS: The model had higher accuracy when it was validated using corrected images than when it was validated using uncorrected images (96.8% vs 90.8%, P < 0.001). The model's accuracy in detecting polyps in the Kvasir-SEG dataset reached 96%, and the area under the receiver operating characteristic curve was 0.94. CONCLUSION: The proposed model can facilitate the clinical diagnosis of colorectal polyps and improve the quality of colonoscopy.

Insulin-like growth factor-1 and cognition in normoglycemia, prediabetes, and type 2 diabetes mellitus.

BACKGROUND: The relationship between insulin-like growth factor-1 (IGF-1) and cognition has been studied in healthy individuals, but not extensively with regards to insulin resistance and type 2 diabetes mellitus (T2DM). In this retrospective observational study, we investigated relationships of IGF-1 with memory and executive function across people with normoglycemia, prediabetes, and T2DM. METHODS: Data from the Midlife in the United States (MIDUS) study were used. Episodic memory and executive function were assessed using the Brief Test of Adult Cognition by Telephone approximately 21.42 ± 12.10 months prior to measuring IGF-1 levels from a fasting blood sample. Normoglycemia was identified as individuals without a physician diagnosis of diabetes and glycated hemoglobin (HbA1c) ≤5.6%. Prediabetes was identified as those without a physician diagnosis of diabetes and HbA1c between 5.7%-6.4%. T2DM was identified as anyone with a physician diagnosis of diabetes, or HbA1c ≥6.5%, or anyone using an oral hypoglycemic medication. The associations were assessed using linear regressions controlling for age, sex, education, body mass index, C-reactive protein, HbA1c or homeostatic model of insulin resistance, MIDUS wave, exercise, smoking status, sleep quality, alcohol intake, oral hypoglycemic use, and insulin use. RESULTS: The study included 1400 participants, which consisted of 583 normoglycemic (48.4% female, mean age 51.0 ± 12.2 years), 512 prediabetes (58.4% female, mean age 57.3 ± 11.8 years), and 305 T2DM participants (53.8% female, mean age 57.6 ± 11.5 years). Peripheral IGF-1 concentrations were lower (F2,1397 = 28.29, p < 0.001) in people with prediabetes or T2DM, vs. normoglycemia. Participants with prediabetes or T2DM had lower episodic memory (F2,1397 = 9.21, p < 0.001) and executive function (F2,1397 = 20.29, p < 0.001) composite z-scores than people with normoglycemia. Higher IGF-1 concentrations were associated with better executive performance in individuals with prediabetes (ß = 0.115 [0.028, 0.202], p = 0.010), but not in individuals with normoglycemia or T2DM. An interaction between IGF-1 and sex in predicting executive function was observed in the prediabetes group (ß = -0.344, p = 0.042), where the relationship was weaker in females (ß = 0.106 [-0.012, 0.224], p = 0.077) than males (ß = 0.251 [0.123, 0.380], p < 0.001). No associations were seen between IGF-1 and memory. CONCLUSION: The results suggest that peripheral IGF-1 concentrations may be related to executive function, and that the relationship may be sex-specific and dependent on diabetes status.

No association between metformin initiation and incident dementia in older adults newly diagnosed with diabetes.

BACKGROUND: Metformin has been suggested to reduce dementia risk; however, most epidemiologic studies have been limited by immortal time bias or confounding due to disease severity. OBJECTIVES: To investigate the association of metformin initiation with incident dementia using strategies that mitigate these important sources of bias. METHODS: Residents of Ontario, Canada ≥66 years newly diagnosed with diabetes from January 1, 2008 to December 31, 2017 entered this retrospective population-based cohort. To consider the indication for metformin monotherapy initiation, people with hemoglobin A1c of 6.5%-8.0% and estimated glomerular filtration rate ≥45 mL/min/1.73 m2 were selected. Using the landmark method to address immortal time bias, exposure was grouped into "metformin monotherapy initiation within 180 days after new diabetes diagnosis" or "no glucose-lowering medications within 180 days." To address disease latency, 1-year lag time was applied to the end of the 180-day landmark period. Incident dementia was defined using a validated algorithm for Alzheimer's disease and related dementias. Adjusted hazard ratios (aHR) and confidence intervals (CIs) were estimated from propensity-score weighted Cox proportional hazard models. RESULTS: Over mean follow-up of 6.77 years from cohort entry, metformin initiation within 180 days after new diabetes diagnosis (N = 12,331; 978 events; 65,762 person-years) showed no association with dementia risk (aHR [95% CI] = 1.05 [0.96-1.15]), compared to delayed or no glucose-lowering medication initiation (N = 22,369; 1768 events; 117,415 person-years). CONCLUSION: Early metformin initiation was not associated with incident dementia in older adults newly diagnosed with diabetes. The utility of metformin to prevent dementia was not supported.

A Qualitative Analysis of Medical Student Reflections Following Participation in a Canadian Radiation Oncology Studentship.

Exposure to radiation oncology in medical school curricula is limited; thus, mentorship and research opportunities like the Dr. Pamela Catton Summer Studentship Program attempt to bridge this gap and stimulate interest in the specialty. In 2021, the studentship was redesigned as virtual research, mentorship, and case-based discussions due to the COVID-19 pandemic. This study explores the impact of COVID-19 on the studentship, on students' perceptions of the program, and on medical training and career choice. Fifteen studentship completion essays during 2021-2022 were obtained and anonymized. Thematic analysis was performed to interpret the essays with NVivo. Two independent reviewers coded the essays. Themes were established by identifying connections between coded excerpts. Consensus was achieved through multiple rounds of discussion and iteratively reviewing each theme. Representative quotes were used to illustrate the themes. The themes confirmed the studentship was feasible during the pandemic. Perceived benefits of the program included mentorship and networking opportunities; gaining practical and fundamental knowledge in radiation oncology; developing clinical and research skills; and creating positive attitudes towards radiation oncology and the humanistic aspect of the field. The studentship supported medical specialty selection by helping define student values, shaping perceptions of the specialty, and promoting self-reflection upon students' personal needs. This study informs future iterations of the studentship to promote radiation oncology in Canadian medical school curricula. It serves as a model for studentships in other specialties that have limited exposure and similar challenges with medical student recruitment.