The association between glycaemic control during hospitalization and risk of adverse events: A retrospective cohort study.

INTRODUCTION: Hyperglycaemia is common during hospitalization; glycaemic targets in non-critical care settings have not been well studied. We assessed associations between inpatient glycaemic control and adverse events. METHODS: We conducted a retrospective cohort study on non-critically ill medical patients hospitalized in a tertiary care hospital between 2015 and 2018. Mean glycaemia during the first four days of hospitalization was categorized as 4.0-7.0 mmol/L, 7.1-10.0 mmol/L and >10.0 mmol/L. The primary outcome was a composite of adverse events including mortality, infections, acute kidney injury, thromboembolic and cardiovascular events. The secondary outcome was hypoglycaemia, defined as any glycaemia <4.0 mmol/L. Logistic regression was used to assess adverse events, and a Cox proportional hazards model was used to estimate hypoglycaemia risk. RESULTS: Our cohort included 1,368 patients, of whom 407 (29.8%) experienced an adverse event. We did not find associations between glycaemia of 4.0-7.0 mmol/L (adjusted odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.63-1.23) or glycaemia of >10.0 mmol/L (adjusted OR: 0.98, 95% CI: 0.75-1.28) and the occurrence of adverse events, compared to a glycaemia of 7.1-10.0 mmol/L. Glycaemia of >10.0 mmol/L was associated with an increased risk of hypoglycaemia (adjusted hazard ratio [HR]: 1.72, 95% CI: 1.21-2.45). Hypoglycaemia was associated with adverse events (adjusted OR 1.85, 95% CI 1.31-2.60). CONCLUSIONS: Neither glycaemia of 4.0-7.0 mmol/L nor glycaemia of >10.0mmol/L during non-critical care hospitalization was associated with increased adverse events. Glycaemia of >10.0 mmol/L was associated with increased hypoglycaemia, likely due to aggressive glucose lowering. These findings highlight the need for further studies to discern optimal inpatient glycaemic targets.

A retrospective cohort study: do patients with graves' disease need to be euthyroid prior to surgery?

BACKGROUND: The 2016 American Thyroid Association guidelines indicate that patients with Graves' disease who undergo a thyroidectomy should be rendered euthyroid through the use of antithyroid drugs (ATD) prior to surgery to avoid complications such as a thyroid storm. At times, the use of ATDs can have limited efficacy and therefore some patients will inevitably remain biochemically hyperthyroid at the time of surgery. The aim of this study is to assess if hyperthyroid patients undergoing a thyroidectomy are at an increased risk of developing a thyroid storm in comparison to euthyroid patients. Furthermore, this study seeks to establish a correlation between thyroid storm identified by the levels of thyroid hormones (T3 and T4) and the level of thyroid stimulating hormone (TSH). METHODS: A retrospective cohort study was conducted at two Canadian centers, one in Montreal and the other in Nova Scotia. Sixty-seven patients undergoing thyroidectomy for Graves' disease from January 2006 to December 2016 were evaluated. RESULTS: The study comprised 67 participants with a mean age of 46 years (range16-78 years). A total of 78% of patients were on methimazole, 34% on beta-blockers, 27% on potassium iodine solution, 10% on propylthiouracil and 7% on steroids. At the time of surgery 21% were in an overt hyperthyroid state and 33% were in a subclinical hyperthyroid state. The average TSH level of 0.03 mIUL/L (range 0.01-0.23 mIUL/L). Sixteen percent of patients had a TSH level less than 0.01 mIUL/L. The average free T4 level was 29.58 pmol/L (range 11.5-95.2 pmol/L). The average total T3 level was 11.52 nmol/L (range 4.5-29.1 nmol/L) and free T3 level was 6.35 pmol/L (range 6.1-6.6 pmol/L). No patient developed thyroid storm. CONCLUSIONS: In our study, biochemically hyperthyroid patients undergoing thyroidectomy did not develop thyroid storm. Additional studies with larger sample sizes are needed to better understand the risk of thyroid storm in hyperthyroid patients.

Long-Term Use of Long-Acting Insulin Analogs and Breast Cancer Incidence in Women With Type 2 Diabetes.

Purpose The association between long-acting insulin analogs and increased breast cancer risk is uncertain, particularly with the short follow-up in previous studies. We assessed this risk long term in women with type 2 diabetes. Methods A population-based cohort of women 40 years or older, all of whom were treated with long-acting (glargine, detemir) or neutral protamine Hagedorn (NPH) insulin between 2002 and 2012, was formed using the United Kingdom's Clinical Practice Research Datalink. Women were followed until February 2015 or breast cancer diagnosis. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% CIs of incident breast cancer, comparing long-acting insulin analogs with NPH overall, as well as by duration and cumulative dose. Results The cohort included 22,395 women who received insulin treatment, with 321 incident breast cancer events occurring during up to 12 years of follow-up (incidence rate 3.3 per 1,000 person-years). Compared with NPH insulin, insulin glargine was associated with an increased risk of breast cancer (HR, 1.44; 95% CI, 1.11 to 1.85), mainly increasing 5 years after glargine initiation (HR, 2.23; 95% CI, 1.32 to 3.77) and after > 30 prescriptions (HR, 2.29; 95% CI, 1.26 to 4.16). The risk was particularly elevated among prior insulin users (HR, 1.53; 95% CI, 1.10 to 2.12) but not for new users, which included fewer patients and for which one cannot rule out an HR of 1.81. The risk associated with insulin detemir was not significantly elevated (HR, 1.17; 95% CI, 0.77 to 1.77). Conclusion Long-term use of insulin glargine is associated with an increased risk of breast cancer in women with type 2 diabetes. The risk associated with insulin detemir remains uncertain because there are fewer users of this insulin.

The Use of Glyburide Compared With Other Sulfonylureas and the Risk of Cancer in Patients With Type 2 Diabetes.

OBJECTIVE: To determine whether the use of glyburide is associated with an increased risk of cancer compared with the use of other second-generation sulfonylureas among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The U.K. Clinical Practice Research Datalink was used to conduct a cohort study among 52,600 patients newly prescribed glyburide or other second-generation sulfonylureas between 1 January 1988 and 31 July 2013. A time-dependent Cox proportional hazards model was used to estimate adjusted hazard ratios (HRs) and 95% CIs of any cancer associated with the use of glyburide compared with the use of second-generation sulfonylureas. Secondary analyses were conducted to determine whether the association varied with cumulative duration of use and cumulative dose (expressed as defined daily dose [DDD]). RESULTS: During 280,288 person-years of follow-up, 4,105 patients were given a new diagnosis of cancer (incidence rate 14.6 per 1,000 person-years). Overall, when compared with the use of other second-generation sulfonylureas, the use of glyburide was associated with a nonsignificant increased risk of any cancer (HR 1.09 [95% CI 0.98-1.22]). In secondary analyses, duration- and dose-response relationships were observed, with longer cumulative durations and cumulative doses associated with an increased risk of any cancer (>36 months: HR 1.21 [95% CI: 1.03-1.42]; >1,096 DDDs: HR 1.27 [95% CI 1.06-1.51]). CONCLUSIONS: In this population-based cohort study, longer cumulative durations and higher cumulative doses of glyburide were associated with an increased risk of cancer.

Incretin-based drugs and the risk of congestive heart failure.

OBJECTIVE: To determine whether the use of incretin-based drugs, including GLP-1 analogs and dipeptidyl peptidase-4 inhibitors, is associated with an increased risk of congestive heart failure (CHF) among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The U.K. Clinical Practice Research Datalink, linked to the Hospital Episode Statistics database, was used to conduct a cohort study with a nested case-control analysis among patients newly prescribed antidiabetic drugs between 1 January 2007 and 31 March 2012 and no prior history of CHF. Case subjects were defined as patients hospitalized for a first CHF and matched with up to 20 control subjects on age, duration of treated diabetes, calendar year, and time since cohort entry. Conditional logistic regression was used to estimate odds ratios (ORs) with corresponding 95% CIs of incident CHF comparing current use of incretin-based drugs with current use of two or more oral antidiabetic drugs. RESULTS: The cohort consisted of 57,737 patients followed for a mean 2.4 years, during which time 1,118 incident cases of hospitalized CHF were identified (incidence rate 8.1/1,000 person-years). Current use of incretin-based drugs was not associated with an increased risk of CHF (adjusted OR 0.85 [95% CI 0.62-1.16]). Secondary analyses revealed no duration-response relationship (P trend = 0.39). CONCLUSIONS: In our population-based study, incretin-based drug use was not associated with an increased risk of CHF among patients with type 2 diabetes. These findings provide some reassurance, but will need to be replicated in other large-scale studies.

Strategies to optimize participation in diabetes prevention programs following gestational diabetes: a focus group study.

OBJECTIVE: We performed a qualitative study among women within 5 years of Gestational Diabetes (GDM) diagnosis. Our aim was to identify the key elements that would enhance participation in a type 2 diabetes (DM2) prevention program. RESEARCH DESIGN AND METHODS: Potential participants received up to three invitation letters from their GDM physician. Four focus groups were held. Discussants were invited to comment on potential facilitators/barriers to participation and were probed on attitudes towards meal replacement and Internet/social media tools. Recurring themes were identified through qualitative content analysis of discussion transcripts. RESULTS: Among the 1,201 contacted and 79 eligible/interested, 29 women attended a focus group discussion. More than half of discussants were overweight/obese, and less than half were physically active. For DM2 prevention, a strong need for social support to achieve changes in dietary and physical activity habits was expressed. In this regard, face-to-face interactions with peers and professionals were preferred, with adjunctive roles for Internet/social media. Further, direct participation of partners/spouses in a DM2 prevention program was viewed as important to enhance support for behavioural change at home. Discussants highlighted work and child-related responsibilities as potential barriers to participation, and emphasized the importance of childcare support to allow attendance. Meal replacements were viewed with little interest, with concerns that their use would provide a poor example of eating behaviour to children. CONCLUSIONS: Among women within 5 years of a GDM diagnosis who participated in a focus group discussion, participation in a DM2 prevention program would be enhanced by face-to-face interactions with professionals and peers, provision of childcare support, and inclusion of spouses/partners.

Vitamin D deficiency as a potentially modifiable risk factor for thyroid cancer.

BACKGROUND: Vitamin D, classically involved in calcium homeostasis, has garnered recent interest for its potential role in cancer prevention and therapy. Although few risk factors have been established in the development of well-differentiated thyroid carcinoma, some would argue that no clear modifiable risk factor exists. Our study is one of the first to explore the relationship between vitamin D deficiency and thyroid cancer. METHODS: This retrospective cohort study was done at a university-affiliated thyroid cancer centre. In 2010, 212 patients undergoing thyroidectomy had their preoperative 25-hydroxyvitamin D(3) levels recorded in addition to the final pathologies of their resected thyroid nodule. The patients were stratified based on vitamin D status; vitamin D deficiency (VDD), reflecting levels under the established threshold of 37.5 nmol/L; and vitamin D sufficiency (VDS), reflecting levels above it. The primary outcome of malignancy rate was used to compare the proportion of malignant nodules in the VDD versus the VDS groups. RESULTS: The malignancy rate rises when comparing the VDS and VDD groups, from 37.5 (33 of 88) to 75% (9 of 12), respectively, corresponding to a relative risk of 2.0 (p  =  .03, 95% CI 1.07-2.66). CONCLUSION: This is the first study to demonstrate the inverse relationship between VDD and well-differentiated thyroid carcinoma. Larger prospective studies are needed to replicate these results. Should this happen, VDD may be the first modifiable risk factor for thyroid cancer.

The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study.

OBJECTIVE: To determine if the use of pioglitazone is associated with an increased risk of incident bladder cancer in people with type 2 diabetes. DESIGN: Retrospective cohort study using a nested case-control analysis. SETTING: Over 600 general practices in the United Kingdom contributing to the general practice research database. PARTICIPANTS: The cohort consisted of people with type 2 diabetes who were newly treated with oral hypoglycaemic agents between 1 January 1988 and 31 December 2009. All incident cases of bladder cancer occurring during follow-up were identified and matched to up to 20 controls on year of birth, year of cohort entry, sex, and duration of follow-up. Exposure was defined as ever use of pioglitazone, along with measures of duration and cumulative dosage. MAIN OUTCOME MEASURE: Risk of incident bladder cancer associated with use of pioglitazone. RESULTS: The cohort included 115,727 new users of oral hypoglycaemic agents, with 470 patients diagnosed as having bladder cancer during follow-up (rate 89.4 per 100,000 person years). The 376 cases of bladder cancer that were diagnosed beyond one year of follow-up were matched to 6699 controls. Overall, ever use of pioglitazone was associated with an increased rate of bladder cancer (rate ratio 1.83, 95% confidence interval 1.10 to 3.05). The rate increased as a function of duration of use, with the highest rate observed in patients exposed for more than 24 months (1.99, 1.14 to 3.45) and in those with a cumulative dosage greater than 28,000 mg (2.54, 1.05 to 6.14). CONCLUSION: The use of pioglitazone is associated with an increased risk of incident bladder cancer among people with type 2 diabetes.

What are thyroidectomy patients really concerned about?

OBJECTIVE: To better appreciate perioperative concerns affecting patients considering thyroidectomy and to understand how they may vary according to patient characteristics. STUDY DESIGN: Cross-sectional analysis. SETTING: Tertiary referral center. SUBJECTS AND METHODS: The authors recruited patients scheduled for thyroid surgery at the McGill University Thyroid Cancer Center. A total of 148 patients completed the 18-item Western Surgical Concern Inventory-Thyroid (WSCI-T) questionnaire. Psychometrics of the WSCI-T were assessed through a principal component analysis with varimax rotation and reliability analyses. Independent-samples t tests and 2-tailed Pearson correlations were ran, identifying areas of elevated concerns and their relationship to gender, age, and surgical procedure (total vs hemithyroidectomy). RESULTS: The principal component analysis revealed the presence of 3 domains of presurgical concerns on the WSCI-T:Surgery-Related Concerns, Psychosocial Concerns, and Daily-Living Concerns. Reliability coefficients for the WSCI-T Total and subscales were satisfactory. Responses on the WSCI-T indicated on average a moderate overall level of concerns before thyroidectomy. Surgery-Related Concerns was the highest domain of concerns, followed by Daily-Living and Psychosocial Concerns, respectively. Patients were mainly worried about the nodule being cancerous, experiencing a change in voice, and surgical complications. Areas of minor concern included being judged or treated differently, becoming depressed, and feeling embarrassed. Women had higher overall levels of concern than men did. Although there were no significant differences in overall levels of concern according to age and surgical procedure, differences were noted at a subscale and item level. CONCLUSION: This study establishes a mean that will permit adequate physician counseling and a better management of patients' perioperative worries.

Underexpression of mineralocorticoid receptor in colorectal carcinomas and association with VEGFR-2 overexpression.

BACKGROUND: The human mineralocorticoid receptor (MR) is a steroid receptor widely expressed in colorectal mucosa. A significant role for the MR in the reduction of vascular endothelial growth factor receptor-2 (VEGFR-2) mRNA levels has been demonstrated in vitro. To evaluate a potential contribution of MR to colorectal carcinoma progression, we analyzed the expression of MR in relation to VEGFR-2. METHODS: Fresh human colorectal cancer tissue and adjacent normal mucosa were harvested from 48 consecutive patients. MR and VEGFR-2 mRNA expression levels were determined by real-time reverse transcriptase-polymerase chain reaction and correlated with clinicopathological parameters. RESULTS: A decline of MR expression was observed in all carcinomas compared to normal mucosa. Expression of MR was a median of 11-fold lower in carcinoma compared to the normal mucosa, irrespective of the location, size, stage, and differentiation. MR was a median of 20-fold underexpressed in carcinomas with VEGFR-2 overexpression vs only 9-fold in carcinomas with VEGFR-2 underexpression (p = 0.035, Mann-Whitney test). CONCLUSIONS: These findings support the hypothesis that reduction of MR expression may be one of the early events involved in colorectal carcinoma progression. The inverse association between MR and VEGFR-2 expression in carcinoma suggests a potential tumor-suppressive function for MR.