Effective Behavior Change Techniques in Digital Health Interventions for the Prevention or Management of Noncommunicable Diseases: An Umbrella Review.

BACKGROUND: Despite an abundance of digital health interventions (DHIs) targeting the prevention and management of noncommunicable diseases (NCDs), it is unclear what specific components make a DHI effective. PURPOSE: This narrative umbrella review aimed to identify the most effective behavior change techniques (BCTs) in DHIs that address the prevention or management of NCDs. METHODS: Five electronic databases were searched for articles published in English between January 2007 and December 2022. Studies were included if they were systematic reviews or meta-analyses of DHIs targeting the modification of one or more NCD-related risk factors in adults. BCTs were coded using the Behavior Change Technique Taxonomy v1. Study quality was assessed using AMSTAR 2. RESULTS: Eighty-five articles, spanning 12 health domains and comprising over 865,000 individual participants, were included in the review. We found evidence that DHIs are effective in improving health outcomes for patients with cardiovascular disease, cancer, type 2 diabetes, and asthma, and health-related behaviors including physical activity, sedentary behavior, diet, weight management, medication adherence, and abstinence from substance use. There was strong evidence to suggest that credible source, social support, prompts and cues, graded tasks, goals and planning, feedback and monitoring, human coaching and personalization components increase the effectiveness of DHIs targeting the prevention and management of NCDs. CONCLUSIONS: This review identifies the most common and effective BCTs used in DHIs, which warrant prioritization for integration into future interventions. These findings are critical for the future development and upscaling of DHIs and should inform best practice guidelines.

Digital health interventions (DHIs) that use technology to deliver lifestyle support for the prevention or treatment of noncommunicable diseases (NCDs) have grown in popularity and number in recent years. However, it is unclear what aspects make a DHI effective in changing lifestyle behaviors and improving health. The aim of this study was to review the existing scientific evidence to identify effective components in DHIs that address the prevention or management of NCDs and summarize the best available evidence to date. We conducted a comprehensive electronic search for peer-reviewed systematic reviews and meta-analyses published in English between January 1, 2007 and December 31, 2022. We systematically extracted details of the reviews and the intervention components and summarized the effectiveness of components for each health domain, prioritizing the best available evidence. Eighty-five articles, spanning 12 health domains and summarizing evidence from over 865,000 individual participants, were included in the review. We found good evidence that DHIs are effective in preventing and treating NCDs. Specific intervention components that are effective and should be prioritized for inclusion in future DHIs include: using a credible source; social support; prompts and cues; graded tasks; goals and planning, feedback and monitoring, human coaching and personalization.

Engagement With a Mobile Phone-Based Life Skills Intervention for Adolescents and Its Association With Participant Characteristics and Outcomes: Tree-Based Analysis.

BACKGROUND: Mobile phone-delivered life skills programs are an emerging and promising way to promote mental health and prevent substance use among adolescents, but little is known about how adolescents actually use them. OBJECTIVE: The aim of this study is to determine engagement with a mobile phone-based life skills program and its different components, as well as the associations of engagement with adolescent characteristics and intended substance use and mental health outcomes. METHODS: We performed secondary data analysis on data from the intervention group (n=750) from a study that compared a mobile phone-based life skills intervention for adolescents recruited in secondary and upper secondary school classes with an assessment-only control group. Throughout the 6-month intervention, participants received 1 SMS text message prompt per week that introduced a life skills topic or encouraged participation in a quiz or individual life skills training or stimulated sharing messages with other program participants through a friendly contest. Decision trees were used to identify predictors of engagement (use and subjective experience). The stability of these decision trees was assessed using a resampling method and by graphical representation. Finally, associations between engagement and intended substance use and mental health outcomes were examined using logistic and linear regression analyses. RESULTS: The adolescents took part in half of the 50 interactions (mean 23.6, SD 15.9) prompted by the program, with SMS text messages being the most used and contests being the least used components. Adolescents who did not drink in a problematic manner and attended an upper secondary school were the ones to use the program the most. Regarding associations between engagement and intended outcomes, adolescents who used the contests more frequently were more likely to be nonsmokers at follow-up than those who did not (odds ratio 0.86, 95% CI 0.76-0.98; P=.02). In addition, adolescents who read the SMS text messages more attentively were less likely to drink in a problematic manner at follow-up (odds ratio 0.43, 95% CI 1.29-3.41; P=.003). Finally, participants who used the program the most and least were more likely to increase their well-being from baseline to 6-month follow-up compared with those with average engagement (ßs=.39; t586=2.66; P=.008; R2=0.24). CONCLUSIONS: Most of the adolescents participating in a digital life skills program that aimed to prevent substance use and promote mental health engaged with the intervention. However, measures to increase engagement in problem drinkers should be considered. Furthermore, efforts must be made to ensure that interventions are engaging and powerful across different educational levels. First results indicate that higher engagement with digital life skills programs could be associated with intended outcomes. Future studies should apply further measures to improve the reach of lower-engaged participants at follow-up to establish such associations with certainty.

Factors Influencing Adherence to mHealth Apps for Prevention or Management of Noncommunicable Diseases: Systematic Review.

BACKGROUND: Mobile health (mHealth) apps show vast potential in supporting patients and health care systems with the increasing prevalence and economic costs of noncommunicable diseases (NCDs) worldwide. However, despite the availability of evidence-based mHealth apps, a substantial proportion of users do not adhere to them as intended and may consequently not receive treatment. Therefore, understanding the factors that act as barriers to or facilitators of adherence is a fundamental concern in preventing intervention dropouts and increasing the effectiveness of digital health interventions. OBJECTIVE: This review aimed to help stakeholders develop more effective digital health interventions by identifying factors influencing the continued use of mHealth apps targeting NCDs. We further derived quantified adherence scores for various health domains to validate the qualitative findings and explore adherence benchmarks. METHODS: A comprehensive systematic literature search (January 2007 to December 2020) was conducted on MEDLINE, Embase, Web of Science, Scopus, and ACM Digital Library. Data on intended use, actual use, and factors influencing adherence were extracted. Intervention-related and patient-related factors with a positive or negative influence on adherence are presented separately for the health domains of NCD self-management, mental health, substance use, nutrition, physical activity, weight loss, multicomponent lifestyle interventions, mindfulness, and other NCDs. Quantified adherence measures, calculated as the ratio between the estimated intended use and actual use, were derived for each study and compared with the qualitative findings. RESULTS: The literature search yielded 2862 potentially relevant articles, of which 99 (3.46%) were included as part of the inclusion criteria. A total of 4 intervention-related factors indicated positive effects on adherence across all health domains: personalization or tailoring of the content of mHealth apps to the individual needs of the user, reminders in the form of individualized push notifications, user-friendly and technically stable app design, and personal support complementary to the digital intervention. Social and gamification features were also identified as drivers of app adherence across several health domains. A wide variety of patient-related factors such as user characteristics or recruitment channels further affects adherence. The derived adherence scores of the included mHealth apps averaged 56.0% (SD 24.4%). CONCLUSIONS: This study contributes to the scarce scientific evidence on factors that positively or negatively influence adherence to mHealth apps and is the first to quantitatively compare adherence relative to the intended use of various health domains. As underlying studies mostly have a pilot character with short study durations, research on factors influencing adherence to mHealth apps is still limited. To facilitate future research on mHealth app adherence, researchers should clearly outline and justify the app's intended use; report objective data on actual use relative to the intended use; and, ideally, provide long-term use and retention data.

ICD-11: an international classification of diseases for the twenty-first century.

BACKGROUND: The International Classification of Diseases (ICD) has long been the main basis for comparability of statistics on causes of mortality and morbidity between places and over time. This paper provides an overview of the recently completed 11th revision of the ICD, focusing on the main innovations and their implications. MAIN TEXT: Changes in content reflect knowledge and perspectives on diseases and their causes that have emerged since ICD-10 was developed about 30 years ago. Changes in design and structure reflect the arrival of the networked digital era, for which ICD-11 has been prepared. ICD-11's information framework comprises a semantic knowledge base (the Foundation), a biomedical ontology linked to the Foundation and classifications derived from the Foundation. ICD-11 for Mortality and Morbidity Statistics (ICD-11-MMS) is the primary derived classification and the main successor to ICD-10. Innovations enabled by the new architecture include an online coding tool (replacing the index and providing additional functions), an application program interface to enable remote access to ICD-11 content and services, enhanced capability to capture and combine clinically relevant characteristics of cases and integrated support for multiple languages. CONCLUSIONS: ICD-11 was adopted by the World Health Assembly in May 2019. Transition to implementation is in progress. ICD-11 can be accessed at icd.who.int.

High levels of RAI3 expression is linked to shortened survival in esophageal cancer patients.

Expression of the retinoic acid-induced protein 3 (RAI3) has been suggested to predict clinical outcome in a variety of malignancies. However, its role in esophageal cancers remains unclear. Immunohistochemical RAI3 staining was analyzed on tissue microarrays containing 359 esophageal adenocarcinomas (EAC) and 254 esophageal squamous cell carcinomas (ESCC). RAI3 immunostaining was typically absent or weakly detectable in the membranes in benign esophageal tissues. RAI3 staining was higher in malignant than in benign esophagus epithelium. High-levels of RAI3 staining were found in 79.2% of interpretable EACs and 55.9% of ESCCs. In EACs, strong RAI3 staining was associated with advanced pathological tumor stage (p < .0001), high UICC stage (p < .0001), high tumor grade (p = .0133), and positive lymph nodal status (p = .0002). Additionally, high RAI3 staining predicted shortened overall survival of EAC and ESCC patients (p = .0298 and p = .0227). RAI3 overexpression is associated with poor prognosis in esophageal cancers. We propose that RAI3 overexpression might play a biologically relevant role of RAI3 in esophageal cancers.

C-Reactive Protein in the Prediction of Localization of Gastrointestinal Perforation.

AIM: Information regarding the localization of the anatomic site of gastrointestinal (GI) tract perforation is essential for the following surgical procedure. The purpose of this study was to evaluate the significance of C-reactive protein (CRP) and other circulating markers for the prediction of the localization of intra-abdominal hollow organ perforation. METHODS: Measurements of serum markers were analyzed in 423 patients with GI tract perforations, who were divided according to the intraoperative diagnosis into colorectal and upper GI tract perforation groups. RESULTS: Levels of CRP were higher in patients with colorectal perforations than in upper GI tract perforations (p < 0.001). Moreover, high levels of CRP were associated with increased mortality of patients with hollow organ perforations (p = 0.009), which was largely driven by the subset of patients with perforations of the upper GI tract (p = 0.001). CONCLUSION: Increased CRP levels predict worse clinical outcome in patients with intra-abdominal hollow organ perforations and are associated with perforations in the colorectal tract. Thus, CRP might be a useful marker for preoperative risk stratification and prediction of the localization of the perforation site.

The WHO 2016 verbal autopsy instrument: An international standard suitable for automated analysis by InterVA, InSilicoVA, and Tariff 2.0.

BACKGROUND: Verbal autopsy (VA) is a practical method for determining probable causes of death at the population level in places where systems for medical certification of cause of death are weak. VA methods suitable for use in routine settings, such as civil registration and vital statistics (CRVS) systems, have developed rapidly in the last decade. These developments have been part of a growing global momentum to strengthen CRVS systems in low-income countries. With this momentum have come pressure for continued research and development of VA methods and the need for a single standard VA instrument on which multiple automated diagnostic methods can be developed. METHODS AND FINDINGS: In 2016, partners harmonized a WHO VA standard instrument that fully incorporates the indicators necessary to run currently available automated diagnostic algorithms. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality. This VA instrument offers the opportunity to harmonize the automated diagnostic algorithms in the future. CONCLUSIONS: Despite all improvements in design and technology, VA is only recommended where medical certification of cause of death is not possible. The method can nevertheless provide sufficient information to guide public health priorities in communities in which physician certification of deaths is largely unavailable. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality.

Expression of ICAM-1, E-cadherin, periostin and midkine in metastases of pancreatic ductal adenocarcinomas.

Development and progression of malignant tumors is in part characterized by the ability of a tumor cell to overcome cell-cell and cell-matrix adhesion and to disseminate in organs distinct from that in which they originated. This study was undertaken to analyze the clinical significance of the expression of the following cell-cell and cell-matrix adhesion molecules in pancreatic ductal adenocarcinomas (PDACs) and synchronous liver metastases: intercellular adhesion molecule 1 (ICAM-1), E-cadherin, periostin, and midkine (MK). ICAM-1, E-cadherin, periostin and MK expression was analyzed by immunohistochemistry on a tissue microarray containing 34 PDACs and 12 liver metastasis specimens. ICAM-1 expression was predominantly localized in the membranes of the cells and was found in weak to moderate intensities in PDACs and liver metastases. E-cadherin expression was absent in the majority of PDACs and corresponding liver metastases. The secreted proteins periostin and MK were expressed in various intensities in primary cancers and liver metastases. Statistical analysis demonstrated that the expression levels of the analyzed markers were neither significantly associated with metastasis in PDACs nor with clinical outcome of patients. Our study shows that the expression of the cell-cell and cell-matrix adhesion molecules ICAM-1, E-cadherin, periostin and MK was not significantly linked to metastatic disease in PDACs. Moreover, our study excludes the analyzed markers as prognostic markers in PDACs.

[ICD-11-Adapting ICD to the 21st century]. / ICD-11 ­ Anpassung der ICD an das 21. Jahrhundert.

In addition to medical innovations, the International Classification of Diseases (ICD-11) addresses the changing needs of digitized healthcare systems. This article describes the concept and developmental structure of the ICD-11.The new technical structure of the ICD-11 allows for a considerably simplified use of the classification and at the same time significantly improves the ability to record individual health conditions at the desired level of detail. The integration of the entire contents and structural information of the ICD-11 in an ontologically organized all-encompassing structure, the so called "foundation", in combination with the connected online platforms is a step into the future. It simplifies translation and maintenance of the classification and considerably improves consistency, especially between language versions. The foundation also permits the production of use-specific versions, so called linearisations, that facilitate the application of ICD by the relevant user groups.The ICD-11 allows versioning-safe documentation using a unique character string, the unique reference identifier. The ICD-11 has been designed for the current de facto use cases. The content of ICD-11 has been updated and linked to other classifications and terminologies. These innovations enable up-to-date documentation of relevant health information in all areas, aggregation of data and the analysis of examination of interrelationships in health.

Up-regulation of mismatch repair genes MSH6, PMS2 and MLH1 parallels development of genetic instability and is linked to tumor aggressiveness and early PSA recurrence in prostate cancer.

DNA mismatch repair (MMR) is integral to the maintenance of genetic stability. We aimed to evaluate the clinical impact of MMR gene expression in prostate cancer. The MMR genes MSH6, MLH1 and PMS2 were analyzed by immunohistochemistry on a tissue microarray containing 11152 prostate cancer specimens. Results were compared with ETS-related gene status and deletions of PTEN, 3p13, 5q21 and 6q15. MSH6, MLH1 and PMS2 expression was detectable in 89.5%, 85.4% and 85.0% of cancers and was particularly strong in cancers with advanced pathological tumor stage (P < 0.0001 each), high Gleason grade (P < 0.0001 each), nodal metastasis (P ≤ 0.0083) and early biochemical recurrence (P < 0.0001). High levels of MMR gene expression paralleled features of genetic instability, such as the number of genomic deletions per cancer; strong expression of all three MMR genes was found in 24%, 29%, 30%, 33% and 42% of cancers with no, one, two, three or four to five deletions (P < 0.0001). The prognostic value of the analyzed MMR genes was largely driven by the subset of cancers lacking ERG fusion (P < 0.0001), while the prognostic impact of MMR gene overexpression was only marginal in ERG-positive cancers. Multivariate analyses suggested an independent prognostic relevance of MMR genes in ERG-negative prostate cancers when compared with prognostic parameters available at the time of initial biopsy. In conclusion, MMR overexpression is common in prostate cancer and is linked to poor outcome as well as features indicating genetic instability. ERG fusion should be analyzed along with MMR gene expression in potential clinical tests.

The prognostic impact of high Nijmegen breakage syndrome (NBS1) gene expression in ERG-negative prostate cancers lacking PTEN deletion is driven by KPNA2 expression.

The Nijmegen breakage syndrome (NBS1) gene was suggested as a prostate cancer susceptibility gene. This study was undertaken to determine, whether NBS1 expression is linked to clinically or molecularly relevant subgroups of prostate cancer. NBS1 expression was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancer specimens. NBS1 expression was absent or only weakly detectable in benign prostate. In prostate cancers, NBS1 expression was found in 81.3% of interpretable tumors and was considered strong in 41.3% of cases. NBS1 upregulation was tightly linked to ERG-positive cancers (p<0.0001). Within ERG-negative cancers, strong NBS1 immunostaining was linked to advanced pathological tumor stage, high Gleason grade, and positive nodal status (p<0.0001 each), while high NBS1 immunostaining was only weakly associated with advanced pathological tumor stage in ERG-positive cancers (p=0.0099). A comparison with chromosomal deletions revealed a strong NBS1 upregulation in PTEN-deleted cancers, while deletions of 3p13, 5q21 and 6q15 did not affect NBS1 expression. High NBS1 expression was linked to biochemical recurrence in ERG-negative and PTEN non-deleted cancers (p<0.0001), which was largely driven by high KPNA2 karyopherin alpha 2 expression. In conclusion, our study identifies an association of NBS1 expression with surrogates of genomic instability in prostate cancer including TMPRSS2-ERG rearrangements and PTEN deletion. The prognostic impact of NBS1 expression in ERG-negative, PTEN non-deleted cancers was dependent of the expression status of its interaction partner KPNA2.

NY-ESO-1 expression is tightly linked to TMPRSS2-ERG fusion in prostate cancer.

BACKGROUND: NY-ESO-1 has been suggested as therapeutic cancer vaccine in prostate cancer. This study was undertaken to explore the relationship of NY-ESO-1 with tumor phenotype, biochemical recurrence, and molecular subgroups in hormone-naive prostate cancers. METHODS: NY-ESO-1 immunohistochemistry was analyzed on a tissue microarray containing 11,152 prostate cancer samples. Results were compared to clinically follow-up data, ERG status, and deletions on PTEN, 3p13, 5q21, and 6q15. RESULTS: NY-ESO-1 expression was absent in benign prostate glands. In prostate cancer, NY-ESO-1 positivity was found 8.8% of our 8,761 interpretable tumors including 5.8% with weak, 2.5% with moderate, and 0.5% with strong expression. There was a threefold higher rate of NY-ESO-1 expression in ERG fusion positive tumors than in ERG negative cancers (P < 0.0001). There was a significant association with early PSA recurrence, which was largely limited to ERG positive cancers. Within the ERG positive subgroup, high NY-ESO-1 expression was associated with early biochemical recurrence (P = 0.0002) and high Gleason grade (P < 0.0001). In ERG negative cancers, NY-ESO-1 expression was also linked to PTEN (P = 0.0012) and 6q15 deletions (P = 0.0005). CONCLUSIONS: Our observations indicate a tight link of NY-ESO-1 expression to ERG activation and (to a lesser extent) PTEN- and 6q15-deletions in prostate cancer. The impact of these interactions on the likelihood of response to immunotherapy is unclear. The prognostic impact of NY-ESO-1 expression is little and not independent of histologic variables.

Sequential neoadjuvant chemoradiotherapy (CRT) followed by curative surgery vs. primary surgery alone for resectable, non-metastasized pancreatic adenocarcinoma: NEOPA- a randomized multicenter phase III study (NCT01900327, DRKS00003893, ISRCTN82191749).

BACKGROUND: Median OS after surgery in curative intent for non-metastasized pancreas cancer ranges under study conditions from 17.9 months to 23.6 months. Tumor recurrence occurs locally, at distant sites (liver, peritoneum, lungs), or both. Observational and autopsy series report local recurrence rates of up to 87% even after potentially "curative" R0 resection. To achieve better local control, neoadjuvant CRT has been suggested for preoperative tumour downsizing, to elevate the likelihood of curative, margin-negative R0 resection and to increase the OS rate. However, controlled, randomized trials addressing the impact of neoadjuvant CRT survival do not exist. METHODS/DESIGN: The underlying hypothesis of this randomized, two-armed, open-label, multicenter, phase III trial is that neoadjuvant CRT increases the three-year overall survival by 12% compared to patients undergoing upfront surgery for resectable pancreatic cancer. A rigorous, standardized technique of histopathologically handling Whipple specimens will be applied at all participating centers. Overall, 410 patients (n=205 in each study arm) will be enrolled in the trial, taking into regard an expected drop out rate of 7% and allocated either to receive neoadjuvant CRT prior to surgery or to undergo surgery alone. Circumferential resection margin status, i.e. R0 and R1 rates, respectively, surgical resectability rate, local and distant disease-free and global survival, and first site of tumor recurrence constitute further essential endpoints of the trial. DISCUSSION: For the first time, the NEOPA study investigates the impact of neoadjuvant CRT on survival of resectable pancreas head cancer in a prospectively randomized manner. The results of the study have the potential to change substantially the treatment regimen of pancreas cancer. TRIAL REGISTRATION: Clinical Trial gov: NCT01900327, DRKS00003893, ISRCTN82191749.

Two decades of the International Classification of Functioning, Disability and Health (ICF) in health research: a bibliometric analysis.

Introduction: We conducted a twenty-year bibliometric analysis of scientific literature, focusing on the trends of The International Classification of Functioning, Disability and Health (ICF) use in health research.Methods: We retrieved 3'467 documents published between 2002 and 2022, sourced from the Web of Science Core Collection database. We used the Bibliometrix and VoSviewer tools for descriptive analyses and data visualization.Results: Our findings indicate a significant increase in ICF application since 2011, with an average annual growth rate of 13.19%. Prominent contributions were observed globally, with notable outputs from the U.S., Canada, Germany, the Netherlands, and Switzerland. The Ludwig Maximilian University Munich, Swiss Paraplegic Research, and McMaster University authored a quarter of the documents (24.6%). Collaboration networks of countries and institutions revealed robust partnerships, particularly between Germany and Switzerland. "Rehabilitation" was the most frequently occurring keyword, although a thematic shift towards epidemiology, aging, and health-related quality of life was observed post-2020. While rehabilitation remained the primary thematic focus, literature post-2020 highlighted epidemiology as a growing area of interest.Conclusions: A steady increase in ICF-based research mirrors the rising interest in a biopsychosocial and person-centered approach to healthcare. However, the literature is primarily produced by high-resource countries, with underrepresentation from low and middle-resource countries, suggesting an area of future research to address this discrepancy.

The International Classification of Functioning, Disability and Health (ICF) serves as a universal framework for describing functioning and disability.The increasing application of the ICF in rehabilitation research underscores its value in developing comprehensive, person-centered care plans.By integrating the ICF, rehabilitation programs can better address the multifaceted needs of patients, facilitating improved outcomes in participation and quality of life.The observed thematic shift towards aging and health-related quality of life post-2020 indicates the growing relevance of the ICF in managing the complex health challenges of an aging population.The study also suggests that expanding the ICF implementation in low- and middle-income countries could bridge existing disparities in rehabilitation services, promoting global health equity.

Linking Health Terminologies: A Unified Approach to the WHO Family of International Classifications.

This paper presents an effort by the World Health Organization (WHO) to integrate the reference classifications of the Family of International Classifications (ICD, ICF, and ICHI) into a unified digital framework. The integration was accomplished via an expanded Content Model and a single Foundation that hosts all entities from these classifications, allowing the traditional use cases of individual classifications to be retained while enhancing their combined use. The harmonized WHO-FIC Content Model and the unified Foundation has streamlined the content management, enhanced the web-based tool functionalities, and provided opportunities for linkage with external terminologies and ontologies. This integration promises reduced maintenance cost, seamless joint application, complete representation of health-related concepts while enabling better interoperability with other informatics infrastructures.

Methodologies and key considerations for implementing the International Classification of Diseases-11th revision morbidity coding: insights from a national pilot study in China.

OBJECTIVE: The aim of this study was to disseminate insights from a nationwide pilot of the International Classification of Diseases-11th revision (ICD-11). MATERIALS AND METHODS: The strategies and methodologies employed to implement the ICD-11 morbidity coding in 59 hospitals in China are described. The key considerations for the ICD-11 implementation were summarized based on feedback obtained from the pilot hospitals. Coding accuracy and Krippendorff's alpha reliability were computed based on the coding results in the ICD-11 exam. RESULTS: Among the 59 pilot hospitals, 58 integrated ICD-11 Coding Software into their health information management systems and 56 implemented the ICD-11 in morbidity coding, resulting in 3 723 959 diagnoses for 873 425 patients being coded over a 2-month pilot coding phase. The key considerations in the transition to the ICD-11 in morbidity coding encompassed the enrichment of ICD-11 content, refinement of tools, provision of systematic and tailored training, improvement of clinical documentation, promotion of downstream data utilization, and the establishment of a national process and mechanism for implementation. The overall coding accuracy was 82.9% when considering the entire coding field (including postcoordination) and 92.2% when only one stem code was considered. Krippendorff's alpha was 0.792 (95% CI, 0.788-0.796) and 0.799 (95% CI, 0.795-0.803) with and without consideration of the code sequence, respectively. CONCLUSION: This nationwide pilot study has enhanced national technical readiness for the ICD-11 implementation in morbidity, elucidating key factors warranting careful consideration in future endeavors. The good accuracy and intercoder reliability of the ICD-11 coding achieved following a brief training program underscore the potential for the ICD-11 to reduce training costs and provide high-quality health data. Experiences and lessons learned from this study have contributed to WHO's work on the ICD-11 and can inform other countries when formulating their transition plan.

Risk Factor Analysis for Developing Major Complications Following Esophageal Surgery-A Two-Center Study.

BACKGROUND: Esophagectomy carries a high risk of morbidity and mortality compared to other major surgeries. With the aim of creating an easy-to-use clinical preoperative risk assessment tool and to validate previously described risk factors for major complications following surgery, esophagectomies at two tertiary medical centers were analyzed. METHODS: A total of 450 patients who underwent esophagectomy for esophageal carcinoma at the University Medical Centre, Hamburg, or at the Medical Center University Duisburg-Essen, Germany (January 2008 to January 2020) were retrospectively analyzed. Epidemiological and perioperative data were analyzed to identify the risk factors that impact major complication rates. The primary endpoint of this study was to determine the incidence of major complications. RESULTS: The mean age of the patients was 63 years with a bimodal distribution. There was a male predominance across the cohort (81% vs. 19%, respectively). Alcohol abuse (p = 0.0341), chronic obstructive pulmonary disease (p = 0.0264), and cardiac comorbidity (p = 0.0367) were associated with a significantly higher risk of major complications in the multivariate analysis. Neoadjuvant chemotherapy significantly reduced the risk of major postoperative complications (p < 0.0001). CONCLUSIONS: Various patient-related risk factors increased the rate of major complications following esophagectomy. Patient-tailored prehabilitation programs before esophagectomy that focus on minimizing these risk factors may lead to better surgical outcomes and should be analyzed in further studies.

High mitochondria content is associated with prostate cancer disease progression.

BACKGROUND: Mitochondria are suggested to be important organelles for cancer initiation and promotion. This study was designed to evaluate the prognostic value of MTC02, a marker for mitochondrial content, in prostate cancer. METHODS: Immunohistochemistry of using an antibody against MTC02 was performed on a tissue microarray (TMA) containing 11,152 prostate cancer specimens. Results were compared to histological phenotype, biochemical recurrence, ERG status and other genomic deletions by using our TMA attached molecular information. RESULTS: Tumor cells showed stronger MTC02 expression than normal prostate epithelium. MTC02 immunostaining was found in 96.5% of 8,412 analyzable prostate cancers, including 15.4% tumors with weak, 34.6% with moderate, and 46.5% with strong expression. MTC02 expression was associated with advanced pathological tumor stage, high Gleason score, nodal metastases (p < 0.0001 each), positive surgical margins (p = 0.0005), and early PSA recurrence (p < 0.0001) if all cancers were jointly analyzed. Tumors harboring ERG fusion showed higher expression levels than those without (p < 0.0001). In ERG negative prostate cancers, strong MTC02 immunostaining was linked to deletions of PTEN, 6q15, 5q21, and early biochemical recurrence (p < 0.0001 each). Moreover, multiple scenarios of multivariate analyses suggested an independent association of MTC02 with prognosis in preoperative settings. CONCLUSIONS: Our study demonstrates high-level MTC02 expression in ERG negative prostate cancers harboring deletions of PTEN, 6q15, and 5q21. Additionally, increased MTC02 expression is a strong predictor of poor clinical outcome in ERG negative cancers, highlighting a potentially important role of elevated mitochondrial content for prostate cancer cell biology.