Low-Dose CT-derived Bronchial Parameters in Individuals with Healthy Lungs.

Background CT-derived bronchial parameters have been linked to chronic obstructive pulmonary disease and asthma severity, but little is known about these parameters in healthy individuals. Purpose To investigate the distribution of bronchial parameters at low-dose CT in individuals with healthy lungs from a Dutch general population. Materials and Methods In this prospective study, low-dose chest CT performed between May 2017 and October 2022 were obtained from participants who had completed the second-round assessment of the prospective, longitudinal Imaging in Lifelines study. Participants were aged at least 45 years, and those with abnormal spirometry, self-reported respiratory disease, or signs of lung disease at CT were excluded. Airway lumens and walls were segmented automatically. The square root of the bronchial wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10), luminal area (LA), wall thickness (WT), and wall area percentage were calculated. Associations between sex, age, height, weight, smoking status, and bronchial parameters were assessed using univariable and multivariable analyses. Results The study sample was composed of 8869 participants with healthy lungs (mean age, 60.9 years ± 10.4 [SD]; 4841 [54.6%] female participants), including 3672 (41.4%) never-smokers and 1197 (13.5%) individuals who currently smoke. Bronchial parameters for male participants were higher than those for female participants (Pi10, slope [ß] range = 3.49-3.66 mm; LA, ß range = 25.40-29.76 mm2; WT, ß range = 0.98-1.03 mm; all P < .001). Increasing age correlated with higher Pi10, LA, and WT (r2 range = 0.06-0.09, 0.02-0.01, and 0.02-0.07, respectively; all P < .001). Never-smoking individuals had the lowest Pi10 followed by formerly smoking and currently smoking individuals (3.62 mm ± 0.13, 3.68 mm ± 0.14, and 3.70 mm ± 0.14, respectively; all P < .001). In multivariable regression models, age, sex, height, weight, and smoking history explained up to 46% of the variation in bronchial parameters. Conclusion In healthy individuals, bronchial parameters differed by sex, height, weight, and smoking history; male sex and increasing age were associated with wider lumens and thicker walls. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Emrich and Varga-Szemes in this issue.

Head and neck cancer patients with geriatric deficits are more often non-responders and lost from follow-up in quality of life studies.

OBJECTIVES: To identify associations between frailty and non-response to follow-up questionnaires, in a longitudinal head and neck cancer (HNC) study with patient-reported outcome measures (PROMs). MATERIALS AND METHODS: Patients referred with HNC were included in OncoLifeS, a prospective data-biobank, underwent Geriatric Assessment (GA) and frailty screening ahead of treatment, and were followed up at 3, 6, 12 and 24 months after treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Head and Neck 35. Statistical analysis for factors associated with non-response was done using Generalized Linear Mixed Models. RESULTS: 289 patients were eligible for analysis. Mean age was 68.4 years and 68.5% were male. Restrictions in Activities of Daily Living [OR 4.46 (2.04-9.78)] and Instrumental Activities of Daily Living [OR 4.33 (2.27-8.24)], impaired mobility on Timed Up and Go test [OR 3.95 (1.85-8.45)], cognitive decline [OR 4.85 (2.28-10.35)] and assisted living (OR 5.54 (2.63-11.67)] were significantly associated with non-response. Frailty screening, with Geriatric 8 and Groningen Frailty Indicator, was also associated with non-response [OR, respectively, 2.64 (1.51-4.59) and 2.52 (1.44-4.44)]. All findings remained significant when adjusted for other factors that were significantly associated with non-response, such as higher age, longer study duration and subsequent death. CONCLUSION: Frail HNC patients respond significantly worse to follow-up PROMs. The drop-out and underrepresentation of frail patients in studies may lead to attrition bias, and as a result underestimating the effect sizes of associations. This is of importance when handling and interpreting such data.

Heart Rate Variability in Surgical Patients Experiencing Live Bedside Music; An Explorative Study.

It's known that surgery elicits a stress response involving the autonomic nervous system (ANS) which is important in general recovery but can also have detrimental effects in older patients. Music seems to positively effect postoperative recovery, although the mechanism requires further unravelling. Our objective was to explore the response of the ANS to live bedside music in older surgical patients, by using heart rate variability (HRV) as a proxy. This explorative prospective non-randomized controlled cohort study included 101 older non-cardiac surgical patients, with a median age of 70 (range 60-88 years). HRV was measured in a cohort receiving live bedside music provided by professional musicians and in a control group that did not receive music. HRV was measured pre-intervention, during the intervention, 30 min after the intervention, and again after three hours. Mixed linear modelling was used to assess the effect of the intervention compared to the control group over time. A significant change in both the low and high frequency bands (p = 0.041) and (p = 0.041) respectively, was found over time in the music group compared to the control group indicating relaxation and increased parasympathetic activity in the music group. Other measures revealed a trend but no significant effect was shown. These results provide a first glance and contribute to a better understanding of the effect of music on the recovery of older surgical patients.

Multi-source data approach for personalized outcome prediction in lung cancer screening: update from the NELSON trial.

Trials show that low-dose computed tomography (CT) lung cancer screening in long-term (ex-)smokers reduces lung cancer mortality. However, many individuals were exposed to unnecessary diagnostic procedures. This project aims to improve the efficiency of lung cancer screening by identifying high-risk participants, and improving risk discrimination for nodules. This study is an extension of the Dutch-Belgian Randomized Lung Cancer Screening Trial, with a focus on personalized outcome prediction (NELSON-POP). New data will be added on genetics, air pollution, malignancy risk for lung nodules, and CT biomarkers beyond lung nodules (emphysema, coronary calcification, bone density, vertebral height and body composition). The roles of polygenic risk scores and air pollution in screen-detected lung cancer diagnosis and survival will be established. The association between the AI-based nodule malignancy score and lung cancer will be evaluated at baseline and incident screening rounds. The association of chest CT imaging biomarkers with outcomes will be established. Based on these results, multisource prediction models for pre-screening and post-baseline-screening participant selection and nodule management will be developed. The new models will be externally validated. We hypothesize that we can identify 15-20% participants with low-risk of lung cancer or short life expectancy and thus prevent ~140,000 Dutch individuals from being screened unnecessarily. We hypothesize that our models will improve the specificity of nodule management by 10% without loss of sensitivity as compared to assessment of nodule size/growth alone, and reduce unnecessary work-up by 40-50%.

Influence of Frailty and Life Expectancy on Guideline Adherence and Outcomes in Cutaneous Squamous Cell Carcinoma of the Head and Neck: A Prospective Pilot Study.

BACKGROUND: Cutaneous squamous cell carcinoma is the second most common malignancy of the skin, often occurring in older patients and in the head and neck area (cSCCHN). Age, life expectancy, and frailty are not taken into consideration by current guidelines. OBJECTIVES: The objective of this study was to evaluate the influence of frailty and life expectancy on guideline deviation, treatment outcomes, and quality of life (QoL) after treatment in patients with cSCCHN. METHODS: Patients with cSCCHN were prospectively included. A geriatric assessment was performed, including the Geriatric 8 (G8), Groningen Frailty Indicator, and Timed Up and Go test (TUG). The Lee index was used to predict a limited life expectancy, and the Adult Comorbidity Evaluation-27 was used as a comorbidity index. QoL was assessed by the Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire at three time points. RESULTS: Seventy-seven patients with cSCCHN were included. Frail patients had significantly more high-risk tumours. Guideline deviation occurred in 7.8% and was more common in patients who were frail (G8), with high-risk tumours (≥T2), with a limited life expectancy or an increased TUG. Guideline deviation did not lead more often to progression of disease in our study. No predictors for post-operative complications were found. BaSQoL subscores were very low at each time point and did not change significantly with time in the total group. Frail patients reported more fear of recurrence or new tumours 3 months after treatment, and less concern about other people's skin 6 months after treatment, compared to non-frail patients. Complication rate, gender, or guideline deviation did not affect any subscale scores. CONCLUSIONS: Assessment of frailty and life expectancy can guide physicians and patients in treatment decisions. Deviation from guidelines towards less aggressive treatment schedules can be considered in frail patients with a limited life expectancy, since it did not negatively affect short-term outcomes or QoL in patients with cSCCHN in our study. However, these results should be confirmed by other, larger prospective studies with a longer follow-up period.

Impact of health-related behavioral factors on participation in a cervical cancer screening program: the lifelines population-based cohort.

BACKGROUND: Regular participation in cervical cancer screening is critical to reducing mortality. Although certain sociodemographic factors are known to be associated with one-time participation in screening, little is known about other factors that could be related to regular participation. Therefore, this study evaluated the association between health-related behavioral factors and regular participation in cervical cancer screening. METHODS: The Lifelines population-based cohort was linked to data for cervical cancer screening from the Dutch Nationwide Pathology Databank. We included women eligible for all four screening rounds between 2000 and 2019, classifying them as regular (4 attendances), irregular (1-3 attendances), and never participants. Multinomial logistic regression was performed to evaluate the association between behavioral factors and participation regularity, with adjustment made for sociodemographic factors. RESULTS: Of the 48,325 included women, 55.9%, 35.1%, and 9% were regular, irregular, and never screening participants. After adjustment for sociodemographic factors, the likelihood of irregular or never screening participation was increased by smoking, obesity, marginal or inadequate sleep duration, alcohol consumption and low physical activity, while it was decreased by hormonal contraception use. CONCLUSION: An association exists between unhealthy behavioral factors and never or irregular participation in cervical cancer screening.

Dutch National Round Robin Trial on Plasma-Derived Circulating Cell-Free DNA Extraction Methods Routinely Used in Clinical Pathology for Molecular Tumor Profiling.

BACKGROUND: Efficient recovery of circulating tumor DNA (ctDNA) depends on the quantity and quality of circulating cell-free DNA (ccfDNA). Here, we evaluated whether various ccfDNA extraction methods routinely applied in Dutch laboratories affect ccfDNA yield, ccfDNA integrity, and mutant ctDNA detection, using identical lung cancer patient-derived plasma samples. METHODS: Aliquots of 4 high-volume diagnostic leukapheresis plasma samples and one artificial reference plasma sample with predetermined tumor-derived mutations were distributed among 14 Dutch laboratories. Extractions of ccfDNA were performed according to local routine standard operating procedures and were analyzed at a central reference laboratory for mutant detection and assessment of ccfDNA quantity and integrity. RESULTS: Mutant molecule levels in extracted ccfDNA samples varied considerably between laboratories, but there was no indication of consistent above or below average performance. Compared to silica membrane-based methods, samples extracted with magnetic beads-based kits revealed an overall lower total ccfDNA yield (-29%; P < 0.0001) and recovered fewer mutant molecules (-41%; P < 0.01). The variant allelic frequency and sample integrity were similar. In samples with a higher-than-average total ccfDNA yield, an augmented recovery of mutant molecules was observed. CONCLUSIONS: In the Netherlands, we encountered diversity in preanalytical workflows with potential consequences on mutant ctDNA detection in clinical practice. Silica membrane-based methodologies resulted in the highest total ccfDNA yield and are therefore preferred to detect low copy numbers of relevant mutations. Harmonization of the extraction workflow for accurate quantification and sensitive detection is required to prevent introduction of technical divergence in the preanalytical phase and reduce interlaboratory discrepancies.

Association between visual emphysema and lung nodules on low-dose CT scan in a Chinese Lung Cancer Screening Program (Nelcin-B3).

OBJECTIVES: This study aimed to evaluate the association between visual emphysema and the presence of lung nodules, and Lung-RADS category with low-dose CT (LDCT). METHODS: Baseline LDCT scans of 1162 participants from a lung cancer screening study (Nelcin-B3) performed in a Chinese general population were included. The presence, subtypes, and severity of emphysema (at least trace) were visually assessed by one radiologist. The presence, size, and classification of non-calcified lung nodules (≥ 30 mm3) and Lung-RADS category were independently assessed by another two radiologists. Multivariable logistic regression and stratified analyses were performed to estimate the association between emphysema and lung nodules, Lung-RADS category, after adjusting for age, sex, BMI, smoking status, pack-years, and passive smoking. RESULTS: Emphysema and lung nodules were observed in 674 (58.0%) and 424 (36.5%) participants, respectively. Participants with emphysema had a 71% increased risk of having lung nodules (adjusted odds ratios, aOR: 1.71, 95% CI: 1.26-2.31) and 70% increased risk of positive Lung-RADS category (aOR: 1.70, 95% CI: 1.09-2.66) than those without emphysema. Participants with paraseptal emphysema (n = 47, 4.0%) were at a higher risk for lung nodules than those with centrilobular emphysema (CLE) (aOR: 2.43, 95% CI: 1.32-4.50 and aOR: 1.60, 95% CI: 1.23-2.09, respectively). Only CLE was associated with positive Lung-RADS category (p = 0.02). CLE severity was related to a higher risk of lung nodules (ranges aOR: 1.44-2.61, overall p < 0.01). CONCLUSION: In a Chinese general population, visual emphysema based on LDCT is independently related to the presence of lung nodules (≥ 30 mm3) and specifically CLE subtype is related to positive Lung-RADS category. The risk of lung nodules increases with CLE severity. KEY POINTS: • Participants with emphysema had an increased risk of having lung nodules, especially smokers. • Participants with PSE were at a higher risk for lung nodules than those with CLE, but nodules in participants with CLE had a higher risk of positive Lung-RADS category. • The risk of lung nodules increases with CLE severity.

The effect of treatment delay on quality of life and overall survival in head and neck cancer patients.

OBJECTIVE: Head and neck squamous cell carcinomas (HNSCC) are rapidly developing tumours, and substantial delay in treatment initiation is associated with decreased overall survival. The effect of delay on health-related quality of life (HRQOL) is unknown. The aim of this study was to assess the impact of delay on QOL and overall survival. METHODS: Patients with mucosal HNSCC were prospectively included. HRQOL and 2-year overall survival were analysed using linear mixed-model analyses and cox regression, respectively. Delay was defined as care pathway interval (CPI) of ≥30 days between first consultation and treatment initiation. RESULTS: Median CPI was 39 days for the 173 patients included. A trend towards higher HRQOL-scores (indicating better HRQOL) during 2-year follow-up for patients with delay in treatment initiation was visible in the adjusted models (HRQOL summary score-ß: 2.62, 95% CI: 0.57-4.67, p = 0.012). Factors associated with decreased overall survival were moderate comorbidities (HR: 5.10, 95% CI: 1.65-15.76, p = 0.005) and stage-IV tumours (HR: 12.37, 95% CI: 2.81-54.39, p = 0.001). Delay was not associated with worse overall survival. CONCLUSION: Timely treatment initiation is challenging, especially for patients with advanced tumours and initial radiotherapy treatment. Encountering delay in treatment initiation did not result in clinically relevant differences in HRQOL-scores or decreased overall survival during 2-year follow-up.

AI-Driven Model for Automatic Emphysema Detection in Low-Dose Computed Tomography Using Disease-Specific Augmentation.

The objective of this study is to evaluate the feasibility of a disease-specific deep learning (DL) model based on minimum intensity projection (minIP) for automated emphysema detection in low-dose computed tomography (LDCT) scans. LDCT scans of 240 individuals from a population-based cohort in the Netherlands (ImaLife study, mean age ± SD = 57 ± 6 years) were retrospectively chosen for training and internal validation of the DL model. For independent testing, LDCT scans of 125 individuals from a lung cancer screening cohort in the USA (NLST study, mean age ± SD = 64 ± 5 years) were used. Dichotomous emphysema diagnosis based on radiologists' annotation was used to develop the model. The automated model included minIP processing (slab thickness range: 1 mm to 11 mm), classification, and detection maps generation. The data-split for the pipeline evaluation involved class-balanced and imbalanced settings. The proposed DL pipeline showed the highest performance (area under receiver operating characteristics curve) for 11 mm slab thickness in both the balanced (ImaLife = 0.90 ± 0.05) and the imbalanced dataset (NLST = 0.77 ± 0.06). For ImaLife subcohort, the variation in minIP slab thickness from 1 to 11 mm increased the DL model's sensitivity from 75 to 88% and decreased the number of false-negative predictions from 10 to 5. The minIP-based DL model can automatically detect emphysema in LDCTs. The performance of thicker minIP slabs was better than that of thinner slabs. LDCT can be leveraged for emphysema detection by applying disease specific augmentation.

Focal pericoronary adipose tissue attenuation is related to plaque presence, plaque type, and stenosis severity in coronary CTA.

OBJECTIVES: To investigate the association of pericoronary adipose tissue mean attenuation (PCATMA) with coronary artery disease (CAD) characteristics on coronary computed tomography angiography (CCTA). METHODS: We retrospectively investigated 165 symptomatic patients who underwent third-generation dual-source CCTA at 70kVp: 93 with and 72 without CAD (204 arteries with plaque, 291 without plaque). CCTA was evaluated for presence and characteristics of CAD per artery. PCATMA was measured proximally and across the most severe stenosis. Patient-level, proximal PCATMA was defined as the mean of the proximal PCATMA of the three main coronary arteries. Analyses were performed on patient and vessel level. RESULTS: Mean proximal PCATMA was -96.2 ± 7.1 HU and -95.6 ± 7.8HU for patients with and without CAD (p = 0.644). In arteries with plaque, proximal and lesion-specific PCATMA was similar (-96.1 ± 9.6 HU, -95.9 ± 11.2 HU, p = 0.608). Lesion-specific PCATMA of arteries with plaque (-94.7 HU) differed from proximal PCATMA of arteries without plaque (-97.2 HU, p = 0.015). Minimal stenosis showed higher lesion-specific PCATMA (-94.0 HU) than severe stenosis (-98.5 HU, p = 0.030). Lesion-specific PCATMA of non-calcified, mixed, and calcified plaque was -96.5 HU, -94.6 HU, and -89.9 HU (p = 0.004). Vessel-based total plaque, lipid-rich necrotic core, and calcified plaque burden showed a very weak to moderate correlation with proximal PCATMA. CONCLUSIONS: Lesion-specific PCATMA was higher in arteries with plaque than proximal PCATMA in arteries without plaque. Lesion-specific PCATMA was higher in non-calcified and mixed plaques compared to calcified plaques, and in minimal stenosis compared to severe; proximal PCATMA did not show these relationships. This suggests that lesion-specific PCATMA is related to plaque development and vulnerability. KEY POINTS: • In symptomatic patients undergoing CCTA at 70 kVp, PCATMA was higher in coronary arteries with plaque than those without plaque. • PCATMA was higher for non-calcified and mixed plaques compared to calcified plaques, and for minimal stenosis compared to severe stenosis. • In contrast to PCATMA measurement of the proximal vessels, lesion-specific PCATMA showed clear relationships with plaque presence and stenosis degree.

Towards reference values of pericoronary adipose tissue attenuation: impact of coronary artery and tube voltage in coronary computed tomography angiography.

OBJECTIVES: To determine normal pericoronary adipose tissue mean attenuation (PCATMA) values for left the anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) in patients without plaques on coronary CT angiography (cCTA), taking into account tube voltage influence. METHODS: This retrospective study included 192 patients (76 (39.6%) men; median age 49 years (range, 19-79)) who underwent cCTA with third-generation dual-source CT for the suspicion of CAD between 2015 and 2017. We selected patients without plaque on cCTA. PCATMA was measured semi-automatically on cCTA images in the proximal segment of the three main coronary arteries with 10 mm length. Paired t-testing was used to compare PCATMA between combinations of two coronary arteries within each patient, and one-way ANOVA testing was used to compare PCATMA in different kV groups. RESULTS: The overall mean ± standard deviation (SD) PCATMA was - 90.3 ± 11.1 HU. PCATMA in men was higher than that in women: - 88.5 ± 10.5 HU versus - 91.5 ± 11.3 HU (p = 0.001). PCATMA of LAD, LCX, and RCA was - 92.4 ± 11.6 HU, - 88.4 ± 9.9 HU, and - 90.2 ± 11.4 HU, respectively. Pairwise comparison of the arteries showed significant difference in PCATMA: LAD and LCX (p < 0.001), LAD and RCA (p = 0.009), LCX and RCA (p = 0.033). PCATMA of the 70 kV, 80 kV, 90 kV, 100 kV, and 120 kV groups was - 95.6 ± 9.6 HU, - 90.2 ± 11.5 HU, - 87.3 ± 9.9 HU, - 82.7 ± 6.2 HU, and - 79.3 ± 6.8 HU, respectively (p < 0.001). CONCLUSIONS: In patients without plaque on cCTA, PCATMA varied by tube voltage, with minor differences in PCATMA between coronary arteries (LAD, LCX, RCA). PCATMA values need to be interpreted taking into account tube voltage setting. KEY POINTS: • In patients without plaque on cCTA, PCATMA differs slightly by coronary artery (LAD, LCX, RCA). • Tube voltage of cCTA affects PCATMA measurement, with mean PCATMA increasing linearly with increasing kV. • For longitudinal cCTA analysis of PCATMA , the use of equal kV setting is strongly recommended.

Early imaging biomarkers of lung cancer, COPD and coronary artery disease in the general population: rationale and design of the ImaLife (Imaging in Lifelines) Study.

Lung cancer, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD) are expected to cause most deaths by 2050. State-of-the-art computed tomography (CT) allows early detection of lung cancer and simultaneous evaluation of imaging biomarkers for the early stages of COPD, based on pulmonary density and bronchial wall thickness, and of CAD, based on the coronary artery calcium score (CACS), at low radiation dose. To determine cut-off values for positive tests for elevated risk and presence of disease is one of the major tasks before considering implementation of CT screening in a general population. The ImaLife (Imaging in Lifelines) study, embedded in the Lifelines study, is designed to establish the reference values of the imaging biomarkers for the big three diseases in a well-defined general population aged 45 years and older. In total, 12,000 participants will undergo CACS and chest acquisitions with latest CT technology. The estimated percentage of individuals with lung nodules needing further workup is around 1-2%. Given the around 10% prevalence of COPD and CAD in the general population, the expected number of COPD and CAD is around 1000 each. So far, nearly 4000 participants have been included. The ImaLife study will allow differentiation between normal aging of the pulmonary and cardiovascular system and early stages of the big three diseases based on low-dose CT imaging. This information can be finally integrated into personalized precision health strategies in the general population.

The OncoLifeS data-biobank for oncology: a comprehensive repository of clinical data, biological samples, and the patient's perspective.

BACKGROUND: Understanding cancer heterogeneity, its temporal evolution over time, and the outcomes of guided treatment depend on accurate data collection in a context of routine clinical care. We have developed a hospital-based data-biobank for oncology, entitled OncoLifeS (Oncological Life Study: Living well as a cancer survivor), that links routine clinical data with preserved biological specimens and quality of life assessments. The aim of this study is to describe the organization and development of a data-biobank for cancer research. RESULTS: We have enrolled 3704 patients aged ≥ 18 years diagnosed with cancer, of which 45 with hereditary breast-ovarian cancer (70% participation rate) as of October 24th, 2019. The average age is 63.6 ± 14.2 years and 1892 (51.1%) are female. The following data are collected: clinical and treatment details, comorbidities, lifestyle, radiological and pathological findings, and long-term outcomes. We also collect and store various biomaterials of patients as well as information from quality of life assessments. CONCLUSION: Embedding a data-biobank in clinical care can ensure the collection of high-quality data. Moreover, the inclusion of longitudinal quality of life data allows us to incorporate patients' perspectives and inclusion of imaging data provides an opportunity for analyzing raw imaging data using artificial intelligence (AI) methods, thus adding new dimensions to the collected data.

Predicting short- and long-term glycated haemoglobin response after insulin initiation in patients with type 2 diabetes mellitus using machine-learning algorithms.

AIM: To assess the potential of supervised machine-learning techniques to identify clinical variables for predicting short-term and long-term glycated haemoglobin (HbA1c) response after insulin treatment initiation in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We included patients with T2DM from the Groningen Initiative to Analyse Type 2 diabetes Treatment (GIANTT) database who started insulin treatment between 2007 and 2013 and had a minimum follow-up of 2 years. Short- and long-term responses at 6 (±2) and 24 (±2) months after insulin initiation, respectively, were assessed. Patients were defined as good responders if they had a decrease in HbA1c ≥ 5 mmol/mol or reached the recommended level of HbA1c ≤ 53 mmol/mol. Twenty-four baseline clinical variables were used for the analysis and an elastic net regularization technique was used for variable selection. The performance of three traditional machine-learning algorithms was compared for the prediction of short- and long-term responses and the area under the receiver-operating characteristic curve (AUC) was used to assess the performance of the prediction models. RESULTS: The elastic net regularization-based generalized linear model, which included baseline HbA1c and estimated glomerular filtration rate, correctly classified short- and long-term HbA1c response after treatment initiation, with AUCs of 0.80 (95% CI 0.78-0.83) and 0.81 (95% CI 0.79-0.84), respectively, and outperformed the other machine-learning algorithms. Using baseline HbA1c alone, an AUC = 0.71 (95% CI 0.65-0.73) and 0.72 (95% CI 0.66-0.75) was obtained for predicting short-term and long-term response, respectively. CONCLUSIONS: Machine-learning algorithm performed well in the prediction of an individual's short-term and long-term HbA1c response using baseline clinical variables.

HbA1c response after insulin initiation in patients with type 2 diabetes mellitus in real life practice: Identifying distinct subgroups.

AIMS: To identify subgroups of patients with type 2 diabetes mellitus (T2DM) following distinct trajectories of HbA1c after insulin initiation and explore underlying differences in clinical characteristics. MATERIALS AND METHODS: A cohort study was conducted in patients with T2DM initiating insulin in 2007-2013 with a follow-up of 2 to 4 years. Data were collected from the Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) database. The primary outcome was subgroups with different trajectories of HbA1c patterns after insulin initiation, as identified by latent class growth modeling. Differences between subgroups were tested using one-way ANOVA, Kruskal-Wallis or chi-square tests, where appropriate. RESULTS: From 1459 patients, three subgroups with distinct HbA1c patterns were identified. Group 1 (8%) initially showed a moderate decrease followed by an increase in HbA1c 2 years later, despite receiving more comedication. Group 2 (84%) showed a stable decrease. Group 3 (8%) had a high initial level of HbA1c and a rapid decline within the first year, followed by a slow increase thereafter. Group 1 patients were on average 6-7 years younger than patients in groups 2 and 3 and were more likely to receive sulfonylureas than Group 3 patients. Group 3 patients had a shorter diabetes duration and were less well-controlled for HbA1c, systolic blood pressure and LDL-cholesterol at insulin initiation. CONCLUSIONS: Most patients showed a stable HbA1c response, but one out of six patients showed either a poor response, or a rapid initial response only after insulin initiation. Response patterns were associated with age, diabetes duration and risk-factor controls at the time of insulin initiation.

Development and validation of prescribing quality indicators for patients with type 2 diabetes.

AIM: Quality indicators are used to measure whether healthcare professionals act according to guidelines, but few indicators focus on the quality of pharmacotherapy for diabetes. The aim of this study was to develop and validate a set of prescribing quality indicators (PQIs) for type 2 diabetes in primary care, and to apply this set in practice. To take into account the stepwise treatment of chronic disease, clinical action indicators were specifically considered. METHODS: Potential PQIs were derived from clinical practice guidelines and evaluated using the RAND/UCLA Appropriateness Method, a modified Delphi panel. Thereafter, the feasibility of calculating the PQIs was tested in two large Dutch primary care databases including >80 000 diabetes patients in 2012. RESULTS: 32 PQIs focusing on treatment with glucose, lipid, blood pressure and albuminuria lowering drugs, and on vaccination, medication safety and adherence were assessed by ten experts. After the Delphi panel, the final list of twenty PQIs was tested for feasibility. All PQIs definitions were feasible for measuring the quality of medication treatment using these databases. Indicator scores ranged from 18.8% to 90.8% for PQIs focusing on current medication use, clinical action and medication choice, and from 2.1% to 37.2% for PQIs focusing on medication safety. DISCUSSION AND CONCLUSIONS: Twenty PQIs focusing on treatment with glucose, lipid, blood pressure and albuminuria lowering drugs, and on medication safety in type 2 diabetes were developed, considered valid and operationally feasible. Results showed room for improvement, especially in initiation and intensification of treatment as measured with clinical action indicators.

Development and initial validation of prescribing quality indicators for patients with chronic kidney disease.

BACKGROUND: Quality assessment is a key element for improving the quality of care. Currently, a comprehensive indicator set for measuring the quality of medication treatment in patients with chronic kidney disease (CKD) is lacking. Our aim was to develop and validate a set of prescribing quality indicators (PQIs) for CKD care, and to test the feasibility of applying this set in practice. METHODS: Potential indicators were based on clinical practice guidelines and evaluated using the RAND/UCLA Appropriateness Method. This is a structured process in which an expert panel assesses the validity of the indicators. Feasibility was tested in a Dutch primary care database including >4500 diabetes patients with CKD. RESULTS: An initial list of 22 PQIs was assessed by 12 experts. After changing 10 PQIs, adding 2 and rejecting 8, a final list of 16 indicators was accepted by the expert panel as valid. These PQIs focused on the treatment of hypertension, albuminuria, mineral and bone disorder, statin prescribing and possible unsafe medication. The indicators were successfully applied to measure treatment quality in the primary care database, but for some indicators the number of eligible patients was too small for reliable calculation. Results showed that there was room for improvement in the treatment quality of this population. CONCLUSIONS: We developed a set of 16 PQIs for measuring the quality of treatment in CKD patients, which had sufficient content and face validity as well as operational feasibility. These PQIs can be used to point out priority areas for improvement.

Process quality indicators for chronic kidney disease risk management: a systematic literature review.

BACKGROUND AND OBJECTIVES: Quality indicators (QIs) can be used for measuring the quality of actions of healthcare providers. This systematic review gives an overview of such QIs measuring processes of care for chronic kidney disease (CKD), and identifies the QIs that have content, face, operational and/or predictive validity. METHODS: PubMed and Embase were searched using a strategy combining the terms "quality of care," "quality indicators" and "chronic kidney disease". Papers were included if they focused on developing, testing or applying QIs for assessing the quality of care in adult patients with CKD not on renal replacement therapy. RESULTS: Two hundred and seventy-three QIs from thirty-one papers were extracted, including QIs on adequate monitoring of kidney function and vascular risk factors, on indicated treatment, drug safety, adherence and referral to a specialist. The QIs that were considered content, face and operational valid focused on monitoring of glomerular filtration rate, albumin-creatinine ratio, lipid levels and blood pressure, the use of non-steroidal anti-inflammatory drugs, nitrofurantoin and biphosphonates in patients with CKD, and QIs on monitoring haemoglobin and treatment with angiotensin-converting-enzyme-inhibitors/angiotensin-receptor-II-blockers in patients with CKD and comorbidities. No QIs were tested for predictive validity. In addition, only two QIs focused on diet and no other QIs focused on lifestyle management. CONCLUSIONS: Based on this review, sufficiently validated QIs can be selected for measuring the quality of CKD care. This review provides insight in QIs that need further validation, and in areas of care where QIs are still lacking.

Statin use as a moderator on the association between metformin and breast cancer risk in women with type 2 diabetes mellitus.

INTRODUCTION: Metformin and statins are considered as potential agents for prevention of breast cancer, however, existing evidence does not uniformly substantiate this claim, and the data is scarce concerning their interaction in relation to breast cancer risk. This study aims to investigate whether the effect of metformin on breast cancer incidence varied by statin use among women with type 2 diabetes mellitus (T2DM). METHODS: This study included women with T2DM, without a history of cancers, and followed up for more than one year from the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) for the period 1998-2014. The dataset was structured using a person-time approach, where the cumulative medication usage was annually updated for each person. The extended Cox proportional hazards models were employed, reporting adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: During a median follow-up of 5 years, 515 of 29,498 women received a breast cancer diagnosis. Each additional year of metformin or statins use corresponded to a decrease in breast cancer incidence, while the magnitude attenuated over time. Noteworthily, statin use modified the effect of metformin on breast cancer incidence. For instance, after 5 years of follow-up, one-year increase of metformin use among women who used statins for 3 years was linked to a substantially reduced breast cancer risk (HR, 95% CI: 0.88, 0.84-0.93), however, there was no significant decrease in risk for those non-statins users (HR, 95% CI: 0.96, 0.89-1.04). CONCLUSIONS: Extending metformin or statin usage by one year conferred breast cancer protection in women with T2DM. Enhanced protective effect of metformin was observed among those who also use statins. These results suggest the potential of combined metformin and statin therapy as promising breast cancer prevention strategies.