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Introduction: Pre‐invasive squamous lesions of the central airways can progress into invasive lung cancers. Identifying these high‐risk patients could enable detection of invasive lung cancers at an early stage. In this study, we investigated the value of 18F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET) scans in predicting progression in patients with pre‐invasive squamous endobronchial lesions. Methods: In this retrospective study, patients with pre‐invasive endobronchial lesions, who underwent an 18F‐FDG PET scan at the VU University Medical Center Amsterdam, between January 2000 and December 2016, were included. Autofluorescence bronchoscopy (AFB) was used for tissue sampling and was repeated every 3 months. The minimum and median follow‐up was 3 and 46.5 months. Study endpoints were the occurrence of biopsy proven invasive carcinoma, time‐to‐progression and overall survival (OS). Results: A total number of 40 of 225 patients met the inclusion criteria of which 17 (42.5%) patients had a positive baseline 18F‐FDG PET scan. A total of 13 of 17 (76.5%) developed invasive lung carcinoma during follow‐up, with a median time to progression of 5.0 months (range, 3.0–25.0). In 23 (57.5%) patients with a negative 18F‐FDG PET scan at baseline, 6 (26%) developed lung cancer, with a median time to progression of 34.0 months (range, 14.0–42.0 months, p < 0.002). With a median OS of 56.0 months (range, 9.0–60.0 months) versus 49.0 months (range, 6.0–60.0 months) (p = 0.876) for the 18F‐FDG PET positive and negative groups, respectively. Conclusions: Patients with pre‐invasive endobronchial squamous lesions and a positive baseline 18F‐FDG PET scan were at high‐risk for developing lung carcinoma, highlighting that this patient group requires early radical treatment. [ABSTRACT FROM AUTHOR]

Background: We aimed to find the best predictive model for 14-day mortality in antibiotic-treated nursing home residents with dementia and pneumonia by first applying an existing model to the recent PneuMonitor study. Second, we evaluated whether model performance improved by revising variables or adding variables related to recent changes in the care for older people.Methods: The original prognostic model included gender, respiratory rate, respiratory difficulty, pulse rate, decreased alertness, fluid intake, eating dependency, and pressure sores. This model was applied to 380 recent pneumonia episodes in nursing home residents with dementia, updated by considering revising and/or adding variables, internally validated using bootstrapping, and transformed into a simplified risk score that can be used in clinical practice. Model performance was evaluated by Hosmer-Lemeshow statistics and calibration graphs to assess calibration; and area under the receiver operating characteristic curve (AUC) to assess discrimination.Results: The newer cohort had lower 14-day mortality and was less often dehydrated or malnourished. Median AUC of the original model over the imputed datasets was 0.76 (interquartile range: 0.76-0.77), compared to 0.80 in the old cohort. Extending the model with dehydration, bowel incontinence, increase in eating dependency and cardiovascular history, while removing pressure sores, improved AUC: 0.80 (interquartile range: 0.80-0.81) after internal validation. Calibration remained adequate (Hosmer-Lemeshow statistic: p = .67).Conclusions: In the newer cohort with less severe illness, model performance of the existing model was adequate, but a new extended model distinguished better between residents at low and high mortality risk. [ABSTRACT FROM AUTHOR]

Objective: Gastrointestinal adverse effects occur in 20-30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5-10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects.Research Design and Methods: The study included 286 severe metformin-intolerant and 1,128 metformin-tolerant individuals from the IMI DIRECT (Innovative Medicines Initiative: DIabetes REsearCh on patient straTification) consortium. We assessed the association of patient characteristics, concomitant medication, and the burden of mutations in the SLC29A4 and SLC22A1 genes on odds of intolerance.Results: Women (P < 0.001) and older people (P < 0.001) were more likely to develop metformin intolerance. Concomitant use of transporter-inhibiting drugs increased the odds of intolerance (odds ratio [OR] 1.72, P < 0.001). In an adjusted logistic regression model, the G allele at rs3889348 (SLC29A4) was associated with gastrointestinal intolerance (OR 1.34, P = 0.005). rs3889348 is the top cis-expression quantitative trait locus for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with transporter-inhibiting drugs had more than three times higher odds of intolerance compared with carriers of no G allele and not treated with inhibiting drugs (OR 3.23, P < 0.001). Use of a genetic risk score derived from rs3889348 and SLC22A1 variants found that the odds of intolerance were more than twice as high in individuals who carry three or more risk alleles compared with those carrying none (OR 2.15, P = 0.01).Conclusions: These results suggest that intestinal metformin transporters and concomitant medications play an important role in the gastrointestinal adverse effects of metformin. [ABSTRACT FROM AUTHOR]

Objective Management of type 2 diabetes mellitus (T2DM) requires frequent monitoring of patients. Within a collective care group setting, doubts on the clinical effects of registration are a barrier for full adoption of T2DM registration in general practice. We explored whether full monitoring of biomedical and lifestyle-related target indicators within a care group approach is associated with lower HbA1c levels. Design Observational, real-life cohort study. Setting Primary care data registry from the Hadoks (EerstelijnsZorggroepHaaglanden) care group. Exposure The care group provides general practitioners collectively with organisational support to facilitate structured T2DM primary care. Patients are offered quarterly medical and lifestyle-related consultation. Main outcome measure Full monitoring of each target indicator in patients with T2DM which includes minimally one measure of HbA1c level, systolic blood pressure, LDL, BMI, smoking behaviour and physical exercise between January and December 2014; otherwise, patients were defined as 'incompletely monitored'. HbA1c levels of 8137 fully monitored and 3958 incompletely monitored patients were compared, adjusted for the confounders diabetes duration, age and gender. Since recommended HbA1c values depend on age, medication use and diabetes duration, analyses were stratified into three HbA1c profile groups. Linear multilevel analyses enabled adjustment for general practice. Results Compared with incompletely monitored patients, fully monitored patients had significantly lower HbA1c levels (95% CI) in the first (-2.03 [-2.53 to -1.52] mmol/mol) (-0.19% [-0.23% to -0.14%]), second (-3.36 [-5.28 to -1.43] mmol/mol) (-0.31% [-0.48% to -0.13%]) and third HbA1c profile group (-1.89 [-3.76 to -0.01] mmol/mol) (-0.17% [-0.34% to 0.00%]). Conclusions/interpretation This study shows that in a care group setting, fully monitored patients had significantly lower HbA1c levels compared with incompletely monitored patients. Since this difference might have considerable clinical impact in terms of T2DM-related risks, this might help general practices in care group settings to overcome barriers on adequate registration and thus improve structured T2DM primary care. From population health management perspective, we recommend a systematic approach to adjust the structured care protocol for incompletely monitored subgroups. [ABSTRACT FROM AUTHOR]

Background: Chronic cardiometabolic diseases, including cardiovascular disease (CVD), type 2 diabetes (T2D) and chronic kidney disease (CKD), share many modifiable risk factors and can be prevented using combined prevention programs. Valid risk prediction tools are needed to accurately identify individuals at risk.Objective: We aimed to validate a previously developed non-invasive risk prediction tool for predicting the combined 7-year-risk for chronic cardiometabolic diseases.Design: The previously developed tool is stratified for sex and contains the predictors age, BMI, waist circumference, use of antihypertensives, smoking, family history of myocardial infarction/stroke, and family history of diabetes. This tool was externally validated, evaluating model performance using area under the receiver operating characteristic curve (AUC)-assessing discrimination-and Hosmer-Lemeshow goodness-of-fit (HL) statistics-assessing calibration. The intercept was recalibrated to improve calibration performance.Participants: The risk prediction tool was validated in 3544 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab).Key Results: Discrimination was acceptable, with an AUC of 0.78 (95% CI 0.75-0.81) in men and 0.78 (95% CI 0.74-0.81) in women. Calibration was poor (HL statistic: p < 0.001), but improved considerably after intercept recalibration. Examination of individual outcomes showed that in men, AUC was highest for CKD (0.85 [95% CI 0.78-0.91]) and lowest for T2D (0.69 [95% CI 0.65-0.74]). In women, AUC was highest for CVD (0.88 [95% CI 0.83-0.94)]) and lowest for T2D (0.71 [95% CI 0.66-0.75]).Conclusions: Validation of our previously developed tool showed robust discriminative performance across populations. Model recalibration is recommended to account for different disease rates. Our risk prediction tool can be useful in large-scale prevention programs for identifying those in need of further risk profiling because of their increased risk for chronic cardiometabolic diseases. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the time to insulin initiation in type 2 diabetes mellitus (T2DM) patients treated with oral glucose-lowering agents and to determine the baseline characteristics associated with time to insulin initiation. This was evaluated in T2DM patients with HbA1c levels consistently ≥7.0% during total follow up and in those with fluctuating HbA1c levels around 7.0%. Design and methods: Prospective, observational study was performed, comprising 2418 persons with T2DM aged ≥40 years who entered the Diabetes Care System between 1998 and 2012 with a minimum follow up of at least 3 years, following the first HbA1c level ≥7.0%. Cox regression analyses were performed to assess the determinants of time to insulin initiation. Data related to long-term effects ofinsulin initiation were studied at baseline and at the end of follow up using descriptive summary statistics. Results: Two-thirds of the patients initiated insulin during follow up. The time to insulin varied from 1.2 years (range 0.3-3.1) in patients with HbA1c levels consistently≥7.0% to 5.4 years (range 3.0-7.5) in patients with fluctuating HbA1c levels around 7.0%. Longer diabetes duration (hazard ratio (HR) 1.04 95% CI 1.03-1.05) and lower age (HR 1.00 95% CI 0.99-1.00) at baseline were associated with a shorter time to initiation. More insulin initiators had retinopathy compared with patients that remained on oral glucose-lowering agents during follow up. Conclusion: The time to insulin initiation was short, and most of the patients with HbA1c levels consistently ≥7.0% were initiating insulin. Longer diabetes duration and younger age shortened the time to insulin. [ABSTRACT FROM AUTHOR]

Introduction: Pre-invasive squamous lesions of the central airways can progress into invasive lung cancers. Identifying these high-risk patients could enable detection of invasive lung cancers at an early stage. In this study, we investigated the value of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) scans in predicting progression in patients with pre-invasive squamous endobronchial lesions., Methods: In this retrospective study, patients with pre-invasive endobronchial lesions, who underwent an 18 F-FDG PET scan at the VU University Medical Center Amsterdam, between January 2000 and December 2016, were included. Autofluorescence bronchoscopy (AFB) was used for tissue sampling and was repeated every 3 months. The minimum and median follow-up was 3 and 46.5 months. Study endpoints were the occurrence of biopsy proven invasive carcinoma, time-to-progression and overall survival (OS)., Results: A total number of 40 of 225 patients met the inclusion criteria of which 17 (42.5%) patients had a positive baseline 18 F-FDG PET scan. A total of 13 of 17 (76.5%) developed invasive lung carcinoma during follow-up, with a median time to progression of 5.0 months (range, 3.0-25.0). In 23 (57.5%) patients with a negative 18 F-FDG PET scan at baseline, 6 (26%) developed lung cancer, with a median time to progression of 34.0 months (range, 14.0-42.0 months, p < 0.002). With a median OS of 56.0 months (range, 9.0-60.0 months) versus 49.0 months (range, 6.0-60.0 months) (p = 0.876) for the  18 F-FDG PET positive and negative groups, respectively., Conclusions: Patients with pre-invasive endobronchial squamous lesions and a positive baseline 18 F-FDG PET scan were at high-risk for developing lung carcinoma, highlighting that this patient group requires early radical treatment., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Structured primary diabetes care within a collectively supported setting is associated with better monitoring of biomedical and lifestyle-related target indicators amongst people with type 2 diabetes and with better HbA1c levels. Whether socioeconomic status affects the delivery of care in terms of monitoring and its association with HbA1c levels within this approach, is unclear. This study aims to understand whether, within a structured care approach, (1) socioeconomic categories differ concerning diabetes monitoring as recommended; (2) socioeconomic status modifies the association between monitoring as recommended and HbA1c., Methods: Observational real-life cohort study with primary care registry data from general practitioners within diverse socioeconomic areas, who are supported with the implementation of structured diabetes care. People with type 2 diabetes mellitus were offered quarterly diabetes consultations. "Monitoring as recommended" by professional guidelines implied minimally one annual registration of HbA1c, systolic blood pressure, LDL, BMI, smoking behaviour and physical activity. Regarding socioeconomic status, deprived, advantageous urban and advantageous suburban categories were compared to the intermediate category concerning (a) recommended monitoring; (b) association between recommended monitoring and HbA1c., Results: Aim 1 (n = 13 601 people): Compared to the intermediate socioeconomic category, no significant differences in odds of being monitored as recommended were found in the deprived (OR 0.45 (95% CI 0.19-1.08)), advantageous urban (OR 1.27 (95% CI 0.46-3.54)) and advantageous suburban (OR 2.32 (95% CI 0.88-6.08)) categories. Aim 2 (n = 11 164 people): People with recommended monitoring had significantly lower HbA1c levels than incompletely monitored people (-2.4 (95% CI -2.9; -1.8) mmol/mol). SES modified monitoring-related HbA1c differences, which were significantly higher in the deprived (-3.3 (95% CI -4.3; -2.4) mmol/mol) than the intermediate category (-1.3 (95% CI -2.2; -0.4) mmol/mol)., Conclusions: Within a structured diabetes care setting, socioeconomic status is not associated with recommended monitoring. Socioeconomic differences in the association between recommended monitoring and HbA1c levels advocate further exploration of practice and patient-related factors contributing to appropriate monitoring and for care adjustment to population needs., (© 2020 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd.)

Objective: Gastrointestinal adverse effects occur in 20-30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5-10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects., Research Design and Methods: The study included 286 severe metformin-intolerant and 1,128 metformin-tolerant individuals from the IMI DIRECT (Innovative Medicines Initiative: DIabetes REsearCh on patient straTification) consortium. We assessed the association of patient characteristics, concomitant medication, and the burden of mutations in the SLC29A4 and SLC22A1 genes on odds of intolerance., Results: Women ( P < 0.001) and older people ( P < 0.001) were more likely to develop metformin intolerance. Concomitant use of transporter-inhibiting drugs increased the odds of intolerance (odds ratio [OR] 1.72, P < 0.001). In an adjusted logistic regression model, the G allele at rs3889348 ( SLC29A4 ) was associated with gastrointestinal intolerance (OR 1.34, P = 0.005). rs3889348 is the top cis -expression quantitative trait locus for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with transporter-inhibiting drugs had more than three times higher odds of intolerance compared with carriers of no G allele and not treated with inhibiting drugs (OR 3.23, P < 0.001). Use of a genetic risk score derived from rs3889348 and SLC22A1 variants found that the odds of intolerance were more than twice as high in individuals who carry three or more risk alleles compared with those carrying none (OR 2.15, P = 0.01)., Conclusions: These results suggest that intestinal metformin transporters and concomitant medications play an important role in the gastrointestinal adverse effects of metformin., (© 2019 by the American Diabetes Association.)

Objective: Management of type 2 diabetes mellitus (T2DM) requires frequent monitoring of patients. Within a collective care group setting, doubts on the clinical effects of registration are a barrier for full adoption of T2DM registration in general practice. We explored whether full monitoring of biomedical and lifestyle-related target indicators within a care group approach is associated with lower HbA 1c levels., Design: Observational, real-life cohort study., Setting: Primary care data registry from the Hadoks (EerstelijnsZorggroepHaaglanden) care group., Exposure: The care group provides general practitioners collectively with organisational support to facilitate structured T2DM primary care. Patients are offered quarterly medical and lifestyle-related consultation., Main Outcome Measure: Full monitoring of each target indicator in patients with T2DM which includes minimally one measure of HbA 1c level, systolic blood pressure, LDL, BMI, smoking behaviour and physical exercise between January and December 2014; otherwise, patients were defined as 'incompletely monitored'. HbA 1c levels of 8137 fully monitored and 3958 incompletely monitored patients were compared, adjusted for the confounders diabetes duration, age and gender. Since recommended HbA 1c values depend on age, medication use and diabetes duration, analyses were stratified into three HbA 1c profile groups. Linear multilevel analyses enabled adjustment for general practice., Results: Compared with incompletely monitored patients, fully monitored patients had significantly lower HbA 1c levels (95% CI) in the first (-2.03 [-2.53 to -1.52] mmol/mol) (-0.19% [-0.23% to -0.14%]), second (-3.36 [-5.28 to -1.43] mmol/mol) (-0.31% [-0.48% to -0.13%]) and third HbA 1c profile group (-1.89 [-3.76 to -0.01] mmol/mol) (-0.17% [-0.34% to 0.00%])., Conclusions/interpretation: This study shows that in a care group setting, fully monitored patients had significantly lower HbA 1c levels compared with incompletely monitored patients. Since this difference might have considerable clinical impact in terms of T2DM-related risks, this might help general practices in care group settings to overcome barriers on adequate registration and thus improve structured T2DM primary care. From population health management perspective, we recommend a systematic approach to adjust the structured care protocol for incompletely monitored subgroups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives/hypothesis: To develop a prediction model that can accurately predict the chance of success following revision stapes surgery in patients with recurrent or persistent otosclerosis at 2- to 6-months follow-up and to validate this model internally., Study Design: A retrospective cohort study of prospectively gathered data in a tertiary referral center., Methods: The associations of 11 prognostic factors with treatment success were tested in 705 cases using multivariable logistic regression analysis with backward selection. Success was defined as a mean air-bone gap closure to 10 dB or less. The most relevant predictors were used to derive a clinical prediction rule to determine the probability of success. Internal validation by means of bootstrapping was performed. Model performance indices, including the Hosmer-Lemeshow test, the area under the receiver operating characteristics curve (AUC), and the explained variance were calculated., Results: Success was achieved in 57.7% of cases at 2- to 6-months follow-up. Certain previous surgical techniques, primary causes of failure leading up to revision stapes surgery, and positions of the prosthesis placed during revision surgery were associated with higher success percentages. The clinical prediction rule performed moderately well in the original dataset (Hosmer-Lemeshow P = .78; AUC = 0.73; explained variance = 22%), which slightly decreased following internal validation by means of bootstrapping (AUC = 0.69; explained variance = 13%)., Conclusions: Our study established the importance of previous surgical technique, primary cause of failure, and type of the prosthesis placed during the revision surgery in predicting the probability of success following stapes surgery at 2- to 6-months follow-up., Level of Evidence: 2b. Laryngoscope, 128:2390-2396, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)