Chronic kidney disease and its association with cerebral small vessel disease in the general older hypertensive population.

BACKGROUND: Cerebral small vessel disease can be identified using magnetic resonance imaging, and includes white matter hyperintensities, lacunar infarcts, cerebral microbleeds, and brain atrophy. Cerebral small vessel disease and chronic kidney disease share many risk factors, including hypertension. This study aims to explore an association between chronic kidney disease and cerebral small vessel disease, and also to explore the role of hypertension in this relationship. METHODS: With a cross sectional study design, data from 390 older adults was retrieved from the general population study Good Aging in Skåne. Chronic kidney disease was defined as glomerular filtration rate < 60 ml/min/1,73m2. Associations between chronic kidney disease and magnetic resonance imaging markers of cerebral small vessel disease were explored using logistic regression models adjusted for age and sex. In a secondary analysis, the same calculations were performed with the study sample stratified based on hypertension status. RESULTS: In the whole group, adjusted for age and sex, chronic kidney disease was not associated with any markers of cerebral small vessel disease. After stratification by hypertension status and adjusted for age and sex, we observed that chronic kidney disease was associated with cerebral microbleeds (OR 1.93, CI 1.04-3.59, p-value 0.037), as well as with cortical atrophy (OR 2.45, CI 1.34-4.48, p-value 0.004) only in the hypertensive group. In the non-hypertensive group, no associations were observed. CONCLUSIONS: In this exploratory cross-sectional study, we observed that chronic kidney disease was associated with markers of cerebral small vessel disease only in the hypertensive subgroup of a general population of older adults. This might indicate that hypertension is an important link between chronic kidney disease and cerebral small vessel disease. Further studies investigating the relationship between CKD, CSVD, and hypertension are warranted.

Artificial intelligence-supported screen reading versus standard double reading in the Mammography Screening with Artificial Intelligence trial (MASAI): a clinical safety analysis of a randomised, controlled, non-inferiority, single-blinded, screening accuracy study.

BACKGROUND: Retrospective studies have shown promising results using artificial intelligence (AI) to improve mammography screening accuracy and reduce screen-reading workload; however, to our knowledge, a randomised trial has not yet been conducted. We aimed to assess the clinical safety of an AI-supported screen-reading protocol compared with standard screen reading by radiologists following mammography. METHODS: In this randomised, controlled, population-based trial, women aged 40-80 years eligible for mammography screening (including general screening with 1·5-2-year intervals and annual screening for those with moderate hereditary risk of breast cancer or a history of breast cancer) at four screening sites in Sweden were informed about the study as part of the screening invitation. Those who did not opt out were randomly allocated (1:1) to AI-supported screening (intervention group) or standard double reading without AI (control group). Screening examinations were automatically randomised by the Picture Archive and Communications System with a pseudo-random number generator after image acquisition. The participants and the radiographers acquiring the screening examinations, but not the radiologists reading the screening examinations, were masked to study group allocation. The AI system (Transpara version 1.7.0) provided an examination-based malignancy risk score on a 10-level scale that was used to triage screening examinations to single reading (score 1-9) or double reading (score 10), with AI risk scores (for all examinations) and computer-aided detection marks (for examinations with risk score 8-10) available to the radiologists doing the screen reading. Here we report the prespecified clinical safety analysis, to be done after 80 000 women were enrolled, to assess the secondary outcome measures of early screening performance (cancer detection rate, recall rate, false positive rate, positive predictive value [PPV] of recall, and type of cancer detected [invasive or in situ]) and screen-reading workload. Analyses were done in the modified intention-to-treat population (ie, all women randomly assigned to a group with one complete screening examination, excluding women recalled due to enlarged lymph nodes diagnosed with lymphoma). The lowest acceptable limit for safety in the intervention group was a cancer detection rate of more than 3 per 1000 participants screened. The trial is registered with ClinicalTrials.gov, NCT04838756, and is closed to accrual; follow-up is ongoing to assess the primary endpoint of the trial, interval cancer rate. FINDINGS: Between April 12, 2021, and July 28, 2022, 80 033 women were randomly assigned to AI-supported screening (n=40 003) or double reading without AI (n=40 030). 13 women were excluded from the analysis. The median age was 54·0 years (IQR 46·7-63·9). Race and ethnicity data were not collected. AI-supported screening among 39 996 participants resulted in 244 screen-detected cancers, 861 recalls, and a total of 46 345 screen readings. Standard screening among 40 024 participants resulted in 203 screen-detected cancers, 817 recalls, and a total of 83 231 screen readings. Cancer detection rates were 6·1 (95% CI 5·4-6·9) per 1000 screened participants in the intervention group, above the lowest acceptable limit for safety, and 5·1 (4·4-5·8) per 1000 in the control group-a ratio of 1·2 (95% CI 1·0-1·5; p=0·052). Recall rates were 2·2% (95% CI 2·0-2·3) in the intervention group and 2·0% (1·9-2·2) in the control group. The false positive rate was 1·5% (95% CI 1·4-1·7) in both groups. The PPV of recall was 28·3% (95% CI 25·3-31·5) in the intervention group and 24·8% (21·9-28·0) in the control group. In the intervention group, 184 (75%) of 244 cancers detected were invasive and 60 (25%) were in situ; in the control group, 165 (81%) of 203 cancers were invasive and 38 (19%) were in situ. The screen-reading workload was reduced by 44·3% using AI. INTERPRETATION: AI-supported mammography screening resulted in a similar cancer detection rate compared with standard double reading, with a substantially lower screen-reading workload, indicating that the use of AI in mammography screening is safe. The trial was thus not halted and the primary endpoint of interval cancer rate will be assessed in 100 000 enrolled participants after 2-years of follow up. FUNDING: Swedish Cancer Society, Confederation of Regional Cancer Centres, and the Swedish governmental funding for clinical research (ALF).

False-positive recalls in the prospective Malmö Breast Tomosynthesis Screening Trial.

OBJECTIVES: To evaluate the total number of false-positive recalls, including radiographic appearances and false-positive biopsies, in the Malmö Breast Tomosynthesis Screening Trial (MBTST). METHODS: The prospective, population-based MBTST, with 14,848 participating women, was designed to compare one-view digital breast tomosynthesis (DBT) to two-view digital mammography (DM) in breast cancer screening. False-positive recall rates, radiographic appearances, and biopsy rates were analyzed. Comparisons were made between DBT, DM, and DBT + DM, both in total and in trial year 1 compared to trial years 2 to 5, with numbers, percentages, and 95% confidence intervals (CI). RESULTS: The false-positive recall rate was higher with DBT, 1.6% (95% CI 1.4; 1.8), compared to screening with DM, 0.8% (95% CI 0.7; 1.0). The proportion of the radiographic appearance of stellate distortion was 37.3% (91/244) with DBT, compared to 24.0% (29/121) with DM. The false-positive recall rate with DBT during trial year 1 was 2.6% (95% CI 1.8; 3.5), then stabilized at 1.5% (95% CI 1.3; 1.8) during trial years 2 to 5. The percentage of stellate distortion with DBT was 50% (19/38) trial year 1 compared to 35.0% (72/206) trial years 2 to 5. CONCLUSIONS: The higher false-positive recall rate with DBT compared to DM was mainly due to an increased detection of stellate findings. The proportion of these findings, as well as the DBT false-positive recall rate, was reduced after the first trial year. CLINICAL RELEVANCE STATEMENT: Assessment of false-positive recalls gives information on potential benefits and side effects in DBT screening. KEY POINTS: • The false-positive recall rate in a prospective digital breast tomosynthesis screening trial was higher compared to digital mammography, but still low compared to other trials. • The higher false-positive recall rate with digital breast tomosynthesis was mainly due to an increased detection of stellate findings; the proportion of these findings was reduced after the first trial year.

EMA Review of Daratumumab (Darzalex) for the Treatment of Adult Patients Newly Diagnosed with Multiple Myeloma.

The use of daratumumab in combination with established regimens for the treatment of newly diagnosed multiple myeloma has recently been authorized by the European Medicines Agency based on results from three separate phase III randomized, active controlled, open-label studies that have confirmed enhanced efficacy and tolerability in both transplant-ineligible (MMY3008 and MMY3007) and transplant-eligible (MMY3006) patients, without compromising transplant ability. Trial MMY3008 showed an improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone; the median PFS had not been reached in the daratumumab arm and was 31.9 months in the control arm (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.43-0.73; p < .0001). Trial MMY3007 showed an improvement in PFS when daratumumab was added to bortezomib, melphalan, and prednisone compared with bortezomib, melphalan, and prednisone; PFS had not been reached in the daratumumab arm and was 18.1 months in the control arm (HR, 0.5; 95% CI, 0.38-0.65; p < .0001). In trial MMY3006, daratumumab added to bortezomib, thalidomide, and dexamethasone was compared with bortezomib, thalidomide, and dexamethasone as induction and consolidation treatment prior to autologous stem cell transplant. The stringent complete response rate at day 100 after transplant in the daratumumab group was 29% compared with 20% in the control group (odds ratio, 1.60; 1.21-2.12 95% CI; p = .0010). Overall adverse events were manageable, with an increased rate of neutropenia and infections in the daratumumab arms. Regulatory assessment of efficacy and safety results from trials MMY3006, MMY3007, and MMY3008 confirmed a positive benefit-risk ratio leading to an approval of the extensions of indication. IMPLICATIONS FOR PRACTICE: A set of extensions of indication was recently approved for daratumumab (Darzalex) in the setting of newly diagnosed multiple myeloma in combination with established regimens. Results of the MMY3006, MMY3007, and MMY3008 trials have shown enhanced efficacy and a favorable side effect profile of several daratumumab-based combinations in patients both ineligible and eligible for transplant, without compromising transplant ability. The combinations of daratumumab with either lenalidomide and low-dose dexamethasone or bortezomib, melphalan, and prednisone were approved for transplant-ineligible patients. The combination of daratumumab with bortezomib, thalidomide, and dexamethasone was approved for transplant-eligible patients. These combinations are expected to improve the survival outlook for patients with multiple myeloma, without an unacceptable risk of increase in adverse events, and updated information on progression-free survival and overall survival is expected from the above trials.

Master protocols in clinical trials: a universal Swiss Army knife?

Master protocols combine several sub-trials, each with their own research objectives, which is usually presented as one single clinical trial application. Master protocols have become increasingly popular in oncology and haematology, as either basket, umbrella, or platform trials. Although master protocols are intended to accelerate drug development and to reduce futility, their use poses challenges to ethics committees, patients, study investigators, and competent authorities during the review and authorisation process of a clinical trial application. In this Personal View, we review the experiences of clinical trial applications from two European medical regulators-the Danish Medicines Agency and the German Federal Institute for Drugs and Medical Devices. We view master protocols as a good opportunity to identify new treatment options more quickly, particularly for patients with cancer. However, the complexity of trial documentation, the amount of information resulting from sub-trials, and the volume of changes and amendments made to clinical trial applications can cause issues during trial supervision, and during the analysis and review of a corresponding application for marketing authorisation. We draw attention to the potential issues arising from these trial concepts and propose possible solutions to avoid problems during clinical trial authorisation and trial conduct.

Tumor Characteristics and Molecular Subtypes in Breast Cancer Screening with Digital Breast Tomosynthesis: The Malmö Breast Tomosynthesis Screening Trial.

Background Screening accuracy can be improved with digital breast tomosynthesis (DBT). To further evaluate DBT in screening, it is important to assess the molecular subtypes of the detected cancers. Purpose To describe tumor characteristics, including molecular subtypes, of cancers detected at DBT compared with those detected at digital mammography (DM) in breast cancer screening. Materials and Methods The Malmö Breast Tomosynthesis Screening Trial is a prospective, population-based screening trial comparing one-view DBT with two-view DM. Tumor characteristics were obtained, and invasive cancers were classified according to St Gallen as follows: luminal A-like, luminal B-like human epidermal growth factor receptor (HER)2-negative/HER2-positive, HER2-positive, and triple-negative cancers. Tumor characteristics were compared by mode of detection: DBT alone or DM (ie, DBT and DM or DM alone). χ2 test was used for data analysis. Results Between January 2010 and February 2015, 14 848 women were enrolled (mean age, 57 years ± 10; age range, 40-76 years). In total, 139 cancers were detected; 118 cancers were invasive and 21 were ductal carcinomas in situ. Thirty-seven additional invasive cancers (36 cancers with complete subtypes and stage) were detected at DBT alone, and 81 cancers (80 cancers with complete stage) were detected at DM. No differences were seen between DBT and DM in the distribution of tumor size 20 mm or smaller (86% [31 of 36] vs 85% [68 of 80], respectively; P = .88), node-negative status (75% [27 of 36] vs 74% [59 of 80], respectively; P = .89), or luminal A-like subtype (53% [19 of 36] vs 46% [37 of 81], respectively; P = .48). Conclusion The biologic profile of the additional cancers detected at digital breast tomosynthesis in a large prospective population-based screening trial was similar to those detected at digital mammography, and the majority were early-stage luminal A-like cancers. This indicates that digital breast tomosynthesis screening does not alter the predictive and prognostic profile of screening-detected cancers. © RSNA, 2019.

One-view breast tomosynthesis versus two-view mammography in the Malmö Breast Tomosynthesis Screening Trial (MBTST): a prospective, population-based, diagnostic accuracy study.

BACKGROUND: Digital breast tomosynthesis is an advancement of the mammographic technique, with the potential to increase detection of lesions during breast cancer screening. The main aim of the Malmö Breast Tomosynthesis Screening Trial (MBTST) was to investigate the accuracy of one-view digital breast tomosynthesis in population screening compared with standard two-view digital mammography. METHODS: In this prospective, population-based screening study, of women aged 40-74 years invited to attend national breast cancer screening at Skåne University Hospital, Malmö, Sweden, a random sample was asked to participate in the trial (every third woman who was invited to attend regular screening was invited to participate). Participants had to be able to speak English or Swedish and were excluded from the study if they were pregnant. Participants underwent screening with two-view digital mammography (ie, craniocaudal and mediolateral oblique views) followed by one-view digital breast tomosynthesis with reduced compression in the mediolateral oblique view (with a wide tomosynthesis angle of 50°) at one screening visit. Images were read with masked double reading and scoring by two separate reading groups, one for each method, made up of seven radiologists. Any cancer detected with a malignancy probability score of three or higher by any reader in either group was discussed in a consensus meeting of at least two readers, from which the decision of whether or not to recall the woman for further investigation was made. The primary outcome measures were sensitivity and specificity of breast cancer detection. Secondary outcome measures were screening performance measures of cancer detection, recall, and interval cancers (cancers clinically detected between screenings), and positive predictive value for screen recalls and negative predictive value of each method. Outcomes were analysed in the per-protocol population. Follow-up of the participants for at least 2 years allowed for identification of interval cancers. This trial is registered with ClinicalTrials.gov, number NCT01091545. FINDINGS: Between Jan 27, 2010, and Feb 13, 2015, of 21 691 women invited, 14 851 (68%) agreed to participate. Three women withdrew consent during follow-up and were excluded from the analyses. 139 breast cancers were detected in 137 (<1%) of 14 848 women. Sensitivity was higher for digital breast tomosynthesis than for digital mammography (81·1%, 95% CI 74·2-86·9, vs 60·4%, 52·3-68·0) and specificity was slightly lower for digital breast tomosynthesis than was for digital mammography (97·2%, 95% CI 97·0-97·5, vs 98·1%, 97·9-98·3). The proportion of cancers detected was significantly higher with digital breast tomosynthesis than with digital mammography (8·7 cancers per 1000 women screened, 95% CI 7·3-10·3 vs 6·5 cancers per 1000 screened, 5·2-7·9; p<0·0001). The proportion of women recalled after discussion was higher among cancers detected by digital breast tomosynthesis than for those detected by digital mammography after consensus (3·6%, 95% CI 3·3-3·9 vs 2·5%, 2·2-2·8; p<0·0001). The positive predictive value for screen recalls was 24·1% (95% CI 20·5-28·0) for digital breast tomosynthesis and 25·9% (21·6-30·7) for digital mammography, and the negative predictive value was 99·8% (99·7-99·9) and 99·6% (99·4-99·7), respectively. The proportion of women who developed interval cancers after trial screening was 1·48 cancers per 1000 women screened (95% CI 0·93-2·24). INTERPRETATION: Breast cancer screening by use of one-view digital breast tomosynthesis with a reduced compression force has higher sensitivity at a slightly lower specificity for breast cancer detection compared with two-view digital mammography and has the potential to reduce the radiation dose and screen-reading burden required by two-view digital breast tomosynthesis with two-view digital mammography. FUNDING: The Swedish Cancer Society, The Swedish Research Council, The Breast Cancer Foundation, The Swedish Medical Society, The Crafoord Foundation, The Gunnar Nilsson Cancer Foundation, The Skåne University Hospital Foundation, Governmental funding for clinical research, The South Swedish Health Care Region, The Malmö Hospital Cancer Foundation and The Cancer Foundation at the Department of Oncology, Skåne University Hospital.

Lower age increases the risk of revision for stemmed and resurfacing shoulder hemi arthroplasty.

Background and purpose - The number of patients where shoulder hemiarthroplasty (SHA) is an option is still substantial. Descriptive analyses performed by the Swedish Shoulder Arthroplasty Registry (SSAR) showed that while patients receiving SHA designs, i.e. resurfacing hemi (RH) and stemmed hemi (SH), reported similar shoulder functionality and quality of life, the revision rate for RH (12%) was larger than for SH (6.7%); this difference was studied. Patients and methods - All primary SHA (n = 1,140) for OA reported to SSAR between 1999 and 2009 were analyzed regarding risk factors for revision and PROM outcome, 950 shoulders with primary OA (POA), and 190 secondary OA (SOA). Mean age was 67.4 years (SD 10.8). PROM including WOOS and EQ-5D were collected at 5 years, until December 31, 2014. Results - 76/950 prostheses because of POA and 16/190 prosthesis because of SOA were revised. Age at primary surgery was the main factor that influenced the risk of revision, lower age increased the risk of revision, and was also the explanation for the difference between SH and RH. We also found that SH and RH had similar outcomes measured by PROM, but the POA group had higher scores than the SOA group with a clinically relevant difference of 10% in WOOS. Interpretation - The risk of revision for SH and RH is similar when adjusted for age and does not depend on primary diagnosis or sex. A lower age increases the risk of revision. Patients suffering from POA experience better shoulder functionality than SOA patients irrespective of implant type.

Incidence and prognostic significance of isolated trisomies in adult acute myeloid leukemia: A population-based study from the Swedish AML registry.

OBJECTIVES AND METHODS: To ascertain the incidence/clinical implications of isolated autosomal trisomies in adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry. RESULTS: Of the 3179 cytogenetically informative AMLs diagnosed January 1997-May 2015, 246 (7.7%) had isolated trisomies. The frequency increased by age (2.4% at age 18-60 years vs. 23% at >60 years; P<.0001); the median age was 69 years. The five most common were +8 (4.0%), +13 (0.9%), +11 (0.8%), +21 (0.7%), and +4 (0.5%). Age and gender, types of AML and treatment, and complete remission and early death rates did not differ between the single trisomy and the intermediate risk (IR) groups or among cases with isolated gains of chromosomes 4, 8, 11, 13, or 21. The overall survival (OS) was similar in the single trisomy (median 1.6 years) and IR groups (1.7 years; P=.251). The OS differed among the most frequent isolated trisomies; the median OS was 2.5 years for +4, 1.9 years for +21, 1.5 years for +8, 1.1 years for +11, and 0.8 years for +13 (P=.013). CONCLUSION: AML with single trisomies, with the exception of +13, should be grouped as IR.

RISK FOR LOW VISUAL ACUITY AFTER 1 AND 2 YEARS OF TREATMENT WITH RANIBIZUMAB OR BEVACIZUMAB FOR PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate how patients with neovascular age-related macular degeneration treated with ranibizumab or bevacizumab respond to treatment in daily clinical practice. METHODS: Data from the Swedish Macula Register on the treatment received by 3,912 patients during 2011 to 2014 is reported. Patients' characteristics at the first visit, visual acuity, number of injections, and reason for terminating the treatment if applicable are discussed. Furthermore, the risk of having poor vision (visual acuity under 60 Early Treatment Diabetes Retinopathy Study letters or approximately 20/60 Snellen) is calculated for the treated eye after 1 year and 2 years. RESULTS: The treatment outcome depends on the visual acuity at the first visit. For patients with visual acuity more than 60 letters, the risk of having a visual acuity lower than 60 letters after 1 year or 2 years of treatment is approximately 20%. However, for patients with low visual acuity at diagnosis (fewer than 60 letters), the risk is approximately 60%. The risk of having a visual acuity lower than 60 letters does not depend on the choice of treatment drug. CONCLUSION: Treatment with anti-vascular endothelial growth factor intravitreal injections mainly maintains the visual acuity level, and only approximately 20% and 40% of the patients required vision rehabilitation after 1 year and 2 years, respectively.

False positives in breast cancer screening with one-view breast tomosynthesis: An analysis of findings leading to recall, work-up and biopsy rates in the Malmö Breast Tomosynthesis Screening Trial.

OBJECTIVES: To analyse false positives (FPs) in breast cancer screening with tomosynthesis (BT) vs. mammography (DM). METHODS: The Malmö Breast Tomosynthesis Screening Trial (MBTST) is a prospective population-based study comparing one-view BT to DM in screening. This study is based on the first half of the MBTST population (n = 7,500). Differences in FP recall rate, findings leading to recall, work-up and biopsy rate between cases recalled on BT alone, DM alone and BT+DM were analysed. RESULTS: The FP recall rate was 1.7 % for BT alone (n = 131), 0.9 % for DM alone (n = 69) and 1.1 % for BT + DM (n = 81). The FP recall rate for BT alone was halved after the initial phase of the trial, stabilising at 1.5 %. BT doubled the recall of stellate distortions compared to DM (n = 64 vs. n = 33). There were fewer fibroadenomas and cysts, and the biopsy rate was slightly lower for FP recalled on BT alone compared to DM alone (15.3 % vs. 27.6 %: p = 0.037 and 33.8 % vs. 36.2 %; p = 0.641, respectively). CONCLUSIONS: FPs increased with BT screening mainly due to the recall of stellate distortions. The FP recall rate was still well within the European guidelines and showed evidence of a learning curve. Characterisation of rounded lesions was improved with BT. KEY POINTS: • Tomosynthesis screening gave a higher false-positive recall rate than mammography • There was a decline in the false-positive recall rate for tomosynthesis • The recall due to stellate distortions simulating malignancy was doubled with tomosynthesis • Tomosynthesis found more radial and postoperative scar tissue than mammography • Tomosynthesis is better at characterising rounded lesions.

Measuring mammographic density: comparing a fully automated volumetric assessment versus European radiologists' qualitative classification.

OBJECTIVES: Breast Imaging-Reporting and Data System (BI-RADS) mammographic density categories are associated with considerable interobserver variability. Automated methods of measuring volumetric breast density may reduce variability and be valuable in risk and mammographic screening stratification. Our objective was to assess agreement of mammographic density by a volumetric method with the radiologists' classification. METHODS: Eight thousand seven hundred and eighty-two examinations from the Malmö Breast Tomosynthesis Screening Trial were classified according to BI-RADS, 4th Edition. Volumetric breast density was assessed using automated software for 8433 examinations. Agreement between volumetric breast density and BI-RADS was descriptively analyzed. Agreement between radiologists and between categorical volumetric density and BI-RADS was calculated, rendering kappa values. RESULTS: The observed agreement between BI-RADS scores of different radiologists was 80.9 % [kappa 0.77 (0.76-0.79)]. A spread of volumetric breast density for each BI-RADS category was seen. The observed agreement between categorical volumetric density and BI-RADS scores was 57.1 % [kappa 0.55 (0.53-0.56)]. CONCLUSIONS: There was moderate agreement between volumetric density and BI-RADS scores from European radiologists indicating that radiologists evaluate mammographic density differently than software. The automated method may be a robust and valuable tool; however, differences in interpretation between radiologists and software require further investigation. KEY POINTS: • Agreement between qualitative and software density measurements has not been frequently studied. • There was substantial agreement between different radiologists´ qualitative density assessments. • There was moderate agreement between software and radiologists' density assessments. • Differences in interpretation between software and radiologists require further investigation.

Performance of one-view breast tomosynthesis as a stand-alone breast cancer screening modality: results from the Malmö Breast Tomosynthesis Screening Trial, a population-based study.

OBJECTIVE: To assess the performance of one-view digital breast tomosynthesis (DBT) in breast cancer screening. METHODS: The Malmö Breast Tomosynthesis Screening Trial is a prospective population-based one-arm study with a planned inclusion of 15000 participants; a random sample of women aged 40-74 years eligible for the screening programme. This is an explorative analysis of the first half of the study population (n = 7500). Participants underwent one-view DBT and two-view digital mammography (DM), with independent double reading and scoring. Primary outcome measures were detection rate, recall rate and positive predictive value (PPV). McNemar's test with 95 % confidence intervals was used. RESULTS: Breast cancer was found in sixty-eight women. Of these, 46 cases were detected by both modalities, 21 by DBT alone and one by DM alone. The detection rate for one-view DBT was 8.9/1000 screens (95 % CI 6.9 to 11.3) and 6.3/1000 screens (4.6 to 8.3) for two-view DM (p < 0.0001). The recall rate after arbitration was 3.8 % (3.3 to 4.2) for DBT and 2.6 % (2.3 to 3.0) for DM (p < 0.0001). The PPV was 24 % for both DBT and DM. CONCLUSION: Our results suggest that one-view DBT might be feasible as a stand-alone screening modality. KEY POINTS: One-view DBT as a stand-alone breast cancer screening modality has not been investigated. One-view DBT increased the cancer detection rate significantly. The recall rate increased significantly but was still low. Breast cancer screening with one-view DBT as a stand-alone modality seems feasible.

Prognostic significance of high hyperdiploid and triploid/tetraploid adult acute myeloid leukemia.

To ascertain the clinical implications of high hyperdiploid (HH; 49-65 chromosomes) and triploid/tetraploid (TT; >65 chromosomes) adult acute myeloid leukemia (AML), all such cases were retrieved from the Swedish AML Registry. Of the 3,654 cytogenetically informative cases diagnosed between January 1997 and May 2014, 68 (1.9%) were HH (n = 50)/TT (n = 18). Patients with HH/TT were older than those with intermediate risk (IR) AML (median 71 years vs. 67 years; P = 0.042) and less often had de novo AML (63% vs. 79%; P = 0.004); no such differences were observed between HH/TT and complex karyotype (CK) AML. The overall survival (OS) was similar between patients with HH/TT and CK AML (median 0.9 years vs. 0.6 years; P = 0.082), whereas OS was significantly longer (median 1.6 years; P = 0.028) for IR AML. The OS was shorter for cases with HH than with TT (median 0.6 years vs. 1.4 years; P = 0.032) and for HH/TT AMLs with adverse abnormalities (median 0.8 years vs. 1.1 years; P = 0.044). In conclusion, HH/TT AML is associated with a poor outcome, but chromosome numbers >65 and absence of adverse aberrations seem to translate into a more favorable prognosis. Thus, HH/TT AMLs are clinically heterogeneous and should not automatically be grouped as high risk.

Association of systemic anticholinergic medication use and accelerated decrease in lung function in older adults.

Older adults are frequently exposed to medicines with systemic anticholinergic properties, which are linked to increased risk of negative health outcomes. The association between systemic anticholinergics and lung function has not been reported. The aim of this study was to investigate if exposure to systemic anticholinergics influences lung function in older adults. Participants of the southernmost centres of the Swedish National study on Aging and Care (SNAC) were followed from 2001 to 2021. In total, 2936 subjects (2253 from Good Aging in Skåne and 683 from SNAC-B) were included. An extensive medical examination including spirometry assessments was performed during the study visits. The systemic anticholinergic burden was described using the anticholinergic cognitive burden scale. The effect of new use of systemic anticholinergics on the annual change in forced expiratory volume (FEV1s) was estimated using mixed models. During follow-up, 802 (27.3%) participants were exposed to at least one systemic anticholinergic medicine. On average, the FEV1s of participants without systemic anticholinergic exposure decreased 37.2 ml/year (95% CI [33.8; 40.6]) while participants with low and high exposure lose 47.2 ml/year (95% CI [42.4; 52.0]) and 43.7 ml/year (95% CI [25.4; 62.0]). A novel association between new use of medicines with systemic anticholinergic properties and accelerated decrease in lung function in older adults was found. The accelerated decrease is comparable to that observed in smokers. Studies are needed to further explore this potential side effect of systemic anticholinergics.

Elevated pulse pressure preceded incident chronic kidney disease in the general older population in Sweden.

Arterial stiffness (AS) and chronic kidney disease (CKD) are common in the older population. AS results in increased pulsatile pressure, elevated pulse pressure (PP), and is linked to hypertension. PP is a surrogate for AS. The kidney has low vascular resistance mechanisms, presumably making it vulnerable to the increased pulsatile pressure and hypertension associated with AS. The aims of this study were to investigate the impact of PP elevation on incident CKD (glomerular filtration rate < 60 ml/min/1.73 m2) and all-cause mortality. The data was collected from the general population cohort study "Good Aging in Skåne". Cox proportional hazard regression models adjusted for age, sex, diabetes, and smoking habits were used to investigate the impact of three levels of PP elevation on incident CKD (n = 2693) and all-cause mortality (n = 5253). For PP < 60 mmHg, the median survival time was 18.7 years (event incident CKD) and first quartile survival time (event all-cause mortality) 15.4 years. Elevated PP ≥ 80 mmHg was associated with incident CKD (hazard ratio 1.59, CI 1.28-1.97), but not all-cause mortality. Our results suggest that a finding of PP ≥ 80 mmHg in older age should raise concern of kidney function.

Mild Cognitive Impairment, Reversion Rates, and Associated Factors: Comparison of Two Diagnostic Approaches.

BACKGROUND: As mild cognitive impairment (MCI) is typically used to identify prodromal stages of dementia, it is essential to identify MCI criteria with high diagnostic stability and prediction of dementia. Moreover, further investigation into pinpointing key factors for reversion is required to foresee future prognosis of MCI patients accurately. OBJECTIVE: To explore disparities in diagnostic stability by examining reversion rates produced by two operationalizations of the MCI definition: the widely applied Petersen criteria and a version of the Neuropsychological (NP) criteria and to identify cognitive, lifestyle, and health related factors for reversion. METHODS: MCI was retrospectively classified in a sample from the Swedish community-based study Good Aging in Skåne with the Petersen criteria (n = 744, median follow-up = 7.0 years) and the NP criteria (n = 375, median follow-up, 6.7 years), respectively. Poisson regression models estimated the effect of various factors on the likelihood of incident reversion. RESULTS: Reversion rates were 323/744 (43.4%, 95% confidence intervals (CI): 39.8; 47.0) and 181/375 (48.3% 95% CI: 43.2; 53.5) for the Petersen criteria and NP criteria, respectively. Participants with impairment in a single cognitive domain, regular alcohol consumption, living with someone, older age, and lower body mass index had a higher likelihood of reverting to normal. CONCLUSION: Reversion rates were similar for Petersen and NP criteria indicating that one definition is not superior to the other regarding diagnostic stability. Additionally, the results highlight important aspects such as multiple domain MCI, cohabitation, and the role of alcohol on predicting the trajectory of those diagnosed with MCI.

Prevalence and functional impact of parkinsonian signs in older adults from the Good Aging in Skåne study.

INTRODUCTION: Mild parkinsonian signs (MPS) have been characterized by several definitions, using the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS). We aimed to investigate the prevalence of MPS and their association with functional level and comorbidities in the oldest old. METHOD: Community-dwelling older adults (n = 559, median age 85, range 80-102 years) were examined regarding MPS, possible parkinsonism (PP) and subthreshold parkinsonism (SP) according to four previously used definitions and concerning the impact of parkinsonian signs on cognitive, physical, and autonomic function. MPS, PP and SP are different terms describing a very similar phenomenon and there is no gradation between these. In two of the four definitions more advanced symptoms were categorized as parkinsonism. RESULTS: Median UPDRS score in the whole study group was 10 points (range: 0-58) and was predominated by bradykinesia. MPS/PP/SP were present in 17-85%, and parkinsonism in 33-71% of the cohort. Independently of age and gender, MPS/PP/SP and especially parkinsonism, were associated with a higher risk of fear of falling and accomplished falls, with lower: cognition, ADL, physical activity and quality of life, and with urinary incontinence, obstipation and orthostatic intolerance. CONCLUSIONS: In a population of older adults above 80 years, MPS are highly prevalent as well as more advanced symptoms defined as parkinsonism, and only 9-17% of the cohort is symptom-free. Predominance of bradykinesia in the oldest old might indicate a need for revision of MPS definitions to improve their sensibility.

Cognitive decline and risk of dementia in older adults after diagnosis of chronic obstructive pulmonary disease.

Cognitive screening has been proposed for older adults diagnosed with chronic obstructive pulmonary disease (COPD). Therefore, we examined the change over time in cognitive function and the risk of incident dementia in older adults after COPD diagnosis. A sample of 3,982 participants from the population-based cohort study Good Aging in Skåne was followed for 19 years, and 317 incident COPD cases were identified. The cognitive domains of episodic memory, executive function, and language were assessed using neuropsychological tests. Mixed models for repeated measures and a Cox model were implemented. Participants performed, on average, worse over time on all neuropsychological tests after COPD diagnosis in comparison to those without COPD, although statistical significance differences were only observed for episodic memory and language. The groups had a comparable risk of developing dementia. In conclusion, our results indicate that cognitive screening in the early stages of COPD may be of limited clinical relevance.