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This article examines how digital epidemiology and eHealth coalesce into a powerful health surveillance system that fundamentally changes present notions of body and health. In the age of Big Data and Quantified Self, the conceptual and practical distinctions between individual and population body, personal and public health, surveillance and health care are diminishing. Expanding on Armstrong's concept of "surveillance medicine" to "quantified self medicine" and drawing on my own research on the symbolic power of statistical constructs in medical encounters, this article explores the impact of digital health surveillance on people's perceptions, actions and subjectivities. It discusses the epistemic confusions and paradoxes produced by a health care system that increasingly treats patients as risk profiles and prompts them to do the same, namely to perceive and manage themselves as a bundle of health and security risks. Since these risks are necessarily constructed in reference to epidemiological data that postulate a statistical gaze, they also construct or make-up disembodied "individuals on alert".

Background: Warfarin is the most widely prescribed anticoagulant for the prevention and treatment of thromboembolic events. Although highly effective, the use of warfarin is limited by a narrow therapeutic range combined with a more than ten-fold difference in the dose required for adequate anticoagulation in adults. An optimal dose that leads to a favourable balance between the wanted antithrombotic effect and the risk of bleeding as measured by the prothrombin time International Normalised Ratio (INR) must be found for each patient. A model describing the time-course of the INR response can be used to aid dose selection before starting therapy (a priori dose prediction) and after therapy has been initiated (a posteriori dose revision). Results: In this paper we describe a warfarin decision support tool. It was transferred from a population PKPD-model for warfarin developed in NONMEM to a platform independent tool written in Java. The tool proved capable of solving a system of differential equations that represent the pharmacokinetics and pharmacodynamics of warfarin with a performance comparable to NONMEM. To estimate an a priori dose the user enters information on body weight, age, baseline and target INR, and optionally CYP2C9 and VKORC1 genotype. By adding information about previous doses and INR observations, the tool will suggest a new dose a posteriori through Bayesian forecasting. Results are displayed as the predicted dose per day and per week, and graphically as the predicted INR curve. The tool can also be used to predict INR following any given dose regimen, e.g. a fixed or an individualized loading-dose regimen. Conclusions: We believe that this type of mechanism-based decision support tool could be useful for initiating and maintaining warfarin therapy in the clinic. It will ensure more consistent dose adjustment practices between prescribers, and provide efficient and truly individualized warfarin dosing in both children and adults. [ABSTRACT FROM AUTHOR]

Background: The FSH starting dose is usually chosen according to women's age, anamnesis, clinical criteria and markers of ovarian reserve. Currently used markers include antral follicle count (AFC), which is considered to have a very high performance in predicting ovarian response to FSH. The objective of the present study to elaborate a nomogram based on AFC for the calculation of the appropriate FSH starting dose in IVF cycles., Methods: This is a retrospective study performed at the Mother-Infant Department of Modena University Hospital. IVF patients (n=505) were subjected to blood sampling and transvaginal ultrasound for measurement of serum day3 FSH, estradiol and AFC. The variables predictive of the number of retrieved oocytes were assessed by backwards stepwise multiple regression. The variables reaching the statistical significance were then used in the calculation for the final predictive model., Results: A model based on age, AFC and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting dose lower than 225 IU in 50.2% and 18.1% of patients younger and older than 35 years, respectively., Conclusions: The daily FSH dose may be calculated on the basis of age and two markers of ovarian reserve, namely AFC and FSH, with the last two variables being the most significant predictors. The nomogram seems easily applicable during the daily clinical practice.

Background: The FSH starting dose is usually chosen according to women's age, anamnesis, clinical criteria and markers of ovarian reserve. Currently used markers include antral follicle count (AFC), which is considered to have a very high performance in predicting ovarian response to FSH. The objective of the present study to elaborate a nomogram based on AFC for the calculation of the appropriate FSH starting dose in IVF cycles. Methods: This is a retrospective study performed at the Mother-Infant Department of Modena University Hospital. IVF patients (n=505) were subjected to blood sampling and transvaginal ultrasound for measurement of serum day3 FSH, estradiol and AFC. The variables predictive of the number of retrieved oocytes were assessed by backwards stepwise multiple regression. The variables reaching the statistical significance were then used in the calculation for the final predictive model. Results: A model based on age, AFC and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting dose lower than 225 IU in 50.2% and 18.1% of patients younger and older than 35 years, respectively. Conclusions: The daily FSH dose may be calculated on the basis of age and two markers of ovarian reserve, namely AFC and FSH, with the last two variables being the most significant predictors. The nomogram seems easily applicable during the daily clinical practice. [ABSTRACT FROM AUTHOR]

Background: Cancer patients benefit from Virtual Reality (VR) in burdensome situations, but evidence is scarce for palliative situations. Based on earlier work in palliative care, individualized VR interventions like seeing the patient's home may address a patient's wish to be at home and thus have a greater effect compared to standard VR content. Yet, some patients and relatives may be concerned about their privacy. Also, patient stakeholders raised concerns about triggering depressed mood or homesickness. Aim: To test the feasibility and safety of individualized vs. standard 360°video VR interventions in palliative cancer inpatients. Methods: Prospective observational study with patient-reported outcome measurement using validated instruments of well-being (MDBF), symptoms and psychosocial burden (IPOS), cybersickness (SSQ), presence experience (SPES), subjective benefit (2 items), content analysis of interviews, and field notes. Individualized VR content was recorded with action camcorder-technology to protect the patients' privacy. Results: Seventeen patients participated, median age 65 years (range 20–82), 9 women (53%), 8 single or widowed (47%), 4 childless (23.5%), 4 academics (23.5%), with a median length of stay of 9 days (1–75) in the hematology (10), palliative care (3), or radiotherapy (2) unit of a German university hospital. Eight patients (53.3%) chose their own home environments or family for individualized VR-content. All participants enjoyed the intervention. Compared to standard VR content the individualized VR tended to have a stronger effect on well-being and emotional touch. It was not inferior in terms of psychosocial burden and cybersickness. No subjective and relevant side effects occurred. The patients well tolerated the assessments. However, most patients demanded a lighter headset and a desire for more interactivity. Conclusions: Individualization of VR content shows potential for enhancement of immersion, which improves the VR experience and does not harm in terms of depressed mood or worsening of symptoms. The patients' and family desire for privacy is feasible with the support of family members who recorded the individualized videos, which is easily manageable today. We suggest a pragmatic randomized clinical trial to compare the effects of individualized vs. standard VR-content. Trial registration: Registered at German Clinical Trials Register (Deutsches Register Klinischer Studien; DRKS); registration number: DRKS00032172; registration date: 11/07/2023. [ABSTRACT FROM AUTHOR]

Background: While person-centered care (PCC) includes multiple domains, residential substance use disorder (SUD) treatment clients may value certain domains over others. We sought to identify the PCC domains most valued by former residential SUD treatment clients. We also sought to explore conceptual distinctions between potential theoretical PCC subdomains. Methods: We distributed an online survey via social media to a national convenience sample of former residential SUD treatment clients. Respondents were presented with ten PCC domains in an online survey: (a) access to evidence-based care; (b) integration of care; (c) diversity/respect for other cultures; (d) individualization of care; (e) emotional support; (f) family involvement in treatment; (g) transitional services; (h) aftercare; (i) physical comfort; and (j) information provision. Respondents were asked to select up to two domains they deemed most important to their residential SUD treatment experience. We used descriptive statistics to identify response frequencies and logistic regression to predict relationships between selected domains and respondents' race, gender, relationship status, parenting status, and housing stability. Results: Our final sample included 435 former residential SUD treatment clients. Diversity and respect for different cultures was the most frequently selected domain (29%), followed by integration of care (26%), emotional support (26%), and individualization of care (26%). Provision of information was the least frequently chosen domain (3%). Race and ethnicity were not predictive of selecting respect for diversity. Also, parental status, relationship status and gender were not predictive of selecting family integration. Employment and housing status were not predictive of selecting transitional services. Conclusions: While residential SUD treatment facilities should seek to implement PCC across all domains, our results suggest facilities should prioritize (a) operationalizing diversity, (b) integration of care, and (c) emotional support. Significant heterogeneity exists regarding PCC domains deemed most important to clients. PCC domains valued by clients cannot be easily predicted based on client demographics. [ABSTRACT FROM AUTHOR]

Background: High rates of clinical alarms in the intensive care unit can result in alarm fatigue among staff. Individualization of alarm thresholds is regarded as one measure to reduce non-actionable alarms. The aim of this study was to investigate staff's perceptions of alarm threshold individualization according to patient characteristics and disease status. Methods: This is a cross-sectional survey study (February-July 2020). Intensive care nurses and physicians were sampled by convenience. Data was collected using an online questionnaire. Results: Staff view the individualization of alarm thresholds in the monitoring of vital signs as important. The extent to which alarm thresholds are adapted from the normal range varies depending on the vital sign monitored, the reason for clinical deterioration, and the professional group asked. Vital signs used for hemodynamic monitoring (heart rate and blood pressure) were most subject to alarm individualizations. Staff are ambivalent regarding the integration of novel technological features into alarm management. Conclusions: All relevant stakeholders, including clinicians, hospital management, and industry, must collaborate to establish a "standard for individualization," moving away from ad hoc alarm management to an intelligent, data-driven alarm management. Making alarms meaningful and trustworthy again has the potential to mitigate alarm fatigue – a major cause of stress in clinical staff and considerable hazard to patient safety. Trial registration: The study was registered at ClinicalTrials.gov (NCT03514173) on 02/05/2018. [ABSTRACT FROM AUTHOR]

Background: The potential benefit of exercise in alleviating symptoms of endometriosis is unclear. Still, exercise may be used to empower women and manage disease symptoms. The purpose of this study was to explore how regular supervised group- and individual exercise training, including pelvic floor muscle training (PFMT), is experienced among women with endometriosis after participating in a randomized controlled trial (RCT). Methods: Among 41 women randomized to exercise training for four months, ten women were interviewed about their experiences with exercise training after participation in the trial. The weekly group training was led by women's health physiotherapists and included individualized and progressive muscular strength training of large muscle groups and the pelvic floor muscles, in addition to endurance-, flexibility, and relaxation training. An individual training program followed the same principles as the group training and was to be performed 3–5 times per week, depending on the level of intensity. PFMT was recommended daily. The women also received a group pain management course emphasizing exercise training as self-management. Using inductive reflexive thematic analysis, responses to the question "Did participation in the study change your view of exercise as part of the treatment for endometriosis?" were analyzed. Results: The women brought forward the importance of knowledge about the benefits of exercise to make informed decisions in disease management. Further, the women described how exercise training was perceived as less frightening and manageable when exposed to various intensities, dosages, and types of exercises in a safe and supportive environment. PFMT was especially brought forward as something new and appreciated, and for some of the women, to be performed on days when their bodies could not handle the general exercise training. They also expressed that the supervised exercise brought an extra dimension of belonging through group participation. Conclusions: Individualization and regular supervision seem important to empower women with knowledge about exercise training as self-management and to experience exercise training as safe and non-threatening. Further, creating a sense of belonging through group training may improve social support and build active coping strategies that are essential for disease management of endometriosis. Trial registration: NCT05091268 (registered 23.09.2021). [ABSTRACT FROM AUTHOR]

Background: The Alpe-DPD study (NCT02324452) demonstrated that prospective genotyping and dose-individualization using four alleles in DPYD (DPYD*2A/rs3918290, c.1236G > A/rs75017182, c.2846A > T/rs67376798 and c.1679 T > G/rs56038477) can mitigate the risk of severe fluoropyrimidine toxicity. However, this could not prevent all toxicities. The goal of this study was to identify additional genetic variants, both inside and outside DPYD, that may contribute to fluoropyrimidine toxicity. Methods: Biospecimens and data from the Alpe-DPD study were used. Exon sequencing was performed to identify risk variants inside DPYD. In silico and in vitro analyses were used to classify DPYD variants. A genome-wide association study (GWAS) with severe fluoropyrimidine-related toxicity was performed to identify variants outside DPYD. Association with severe toxicity was assessed using matched-pair analyses for the exon sequencing and logistic, Cox, and ordinal regression analyses for GWAS. Results: Twenty-four non-synonymous, frameshift, and splice site DPYD variants were detected in ten of 986 patients. Seven of these variants (c.1670C > T, c.1913 T > C, c.1925 T > C, c.506delC, c.731A > C, c.1740 + 1G > T, c.763 − 2A > G) were predicted to be deleterious. The carriers of either of these variants showed a trend towards a 2.14-fold (95% CI, 0.41–11.3, P = 0.388) increased risk of severe toxicity compared to matched controls (N = 30). After GWAS of 942 patients, no individual single nucleotide polymorphisms achieved genome-wide significance (P ≤ 5 × 10−8), however, five variants were suggestive of association (P < 5 × 10−6) with severe toxicity. Conclusions: Results from DPYD exon sequencing and GWAS analysis did not identify additional genetic variants associated with severe toxicity, which suggests that testing for single markers at a population level currently has limited clinical value. Identifying additional variants on an individual level is still promising to explain fluoropyrimidine-related severe toxicity. In addition, studies with larger samples sizes, in more diverse cohorts are needed to identify potential clinically relevant genetic variants related to severe fluoropyrimidine toxicity. [ABSTRACT FROM AUTHOR]

Background: The Apple Watch (AW) was the first smartwatch to provide wheelchair user (WCU) specific information on energy expenditure (EE), but was found to be inaccurate (i.e., it underestimated) and imprecise (i.e., the underestimation was variable). Insight is therefore needed into where these inaccuracies/imprecisions originate. Accordingly, the aim of this study was to investigate how much of the variation in AW EE is explained by heart rate (HR), in addition to other factors such as body mass and height, sex, age, physical activity level and disability. Methods: Forty participants (20 WCU, 20 non-disabled) performed three 4-min treadmill wheelchair propulsion stages at different speed-incline combinations, on three separate days, while wearing an AW series 4 (setting: "outdoor push walking pace"). Linear mixed model analyses investigated how much of the variation in AW EE (kcal·min−1) is explained by the fixed effects AW HR (beats·min−1), body mass and height, sex, age, physical activity level and disability. Participant-ID was included as random-intercept effect. The same mixed model analyses were conducted for criterion EE and HR. Marginal R2 (R2m; fixed effects only) and conditional R2 (R2c; fixed and random effects) values were computed. An R2m close to zero indicates that the fixed effects alone do not explain much variation. Results: Although criterion HR explained a significant amount of variation in criterion EE (R2m: 0.44, R2c: 0.92, p < 0.001), AW HR explained little variation in AW EE (R2m: 0.06, R2c: 0.86, p < 0.001). In contrast, body mass and sex explained a significant amount of variation in AW EE (R2m: 0.74, R2c: 0.79, p < 0.001). No further improvements in fit were achieved by adding body height, age, physical activity level or disability to the AW EE model (R2m: 0.75, R2c: 0.79, p = 0.659). Conclusion: Our results remain inconclusive on whether AW heart rate is used as factor to adjust for exercise intensity in the black box AW EE estimation algorithms. In contrast, body mass explained much of the variation in AW EE, indicating that the AW EE estimation algorithm is very reliant on this factor. Future investigations should explore better individualization of EE estimation algorithms. [ABSTRACT FROM AUTHOR]

Background: Many exercise studies, including older adults, do not report all relevant exercise characteristics. Especially the description of exercise intensity is missing and mostly not controlled. This leads to difficulties in interpreting study results and summarizing the evidence in systematic reviews or meta-analyses. Therefore, the aim of the present Delphi study was to gain recommendations about the categorization of exercise intensity and for the conducting and reporting of characteristics in future intervention studies with older adults by experts in exercise science and physiology. Methods: Two hundred ninety-seven international interdisciplinary participants from an EU COST action were invited to participate in three rounds of online questionnaires in April/May 2023. Up to N = 93 experts participated in each round. Round 1 included open-ended questions to solicit possible recommendations and categorizations for light, moderate, vigorous, and high intensity. In round 2, the experts rated their agreement using Likert scales (1–10) on the revealed categories and recommendations. Clusters with a higher average rating of M = 8.0 were summarized into round 3. In the final round, the results were presented for a final rating of agreement (based on a simple majority > 50%). Results: In round 1 a total of 416 qualitative statements were provided from thirteen questions. From round 1 to round 3, a total of 38 items were excluded, with 205 items retained for the final consensus. In round three 37 participants completed the whole questionnaire. The experts showed overall agreement on the final categorizations with 6.7 to 8.8 out of 10 points on the Likert scale. They also showed broad consensus on the relevance of reporting exercise intensity and the recommendations for future conducting and reporting of study results. However, exercise types such as yoga, balance, and coordination training led to conflicting results for categorization into light or moderate. Discussion and implications: The results of the current survey can be used to classify the intensity of exercise and suggest a practical approach that can be adopted by the scientific community and applied when conducting systematic reviews and meta-analysis articles when vital and objective information regarding exercise intensity is lacking from the original article. Highlights: - Experts highlight the importance of reporting exercise intensity for individualization and participant safety - International interdisciplinary participants with expertise in exercise gained a common understanding of the categorization of exercise intensity for future intervention studies with older adults. - Conflicting results for exercise types such as yoga, balance, and coordination training present categorization challenges [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prognosis value of a combined model based on 18F-fluoro-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) baseline and interim parameters in patients with diffuse large B-cell lymphoma (DLBCL). Methods: We retrospectively analyzed the PET metabolic parameters and clinical data of 154 DLBCL patients between December 2015 and October 2020. All of these patients underwent 18F-FDG PET/CT scan before treatment and after three or four courses of chemotherapy. The optimal cut-off values for quantitative variables were determined by the receiver operating characteristic (ROC) curve. The baseline and interim PET/CT parameters, which respectively included maximum standardized uptake value (SUVmax0), total metabolic tumor volume (TMTV0), standardized total metabolic tumor volume (STMTV0), and the distance between the two furthest lesions (Dmax) and total tumor lesion glycolysis (TTLG1), SUVmax1, TMTV1, and the rate of change of SUVmax (%ΔSUVmax), and clinical characteristics were analyzed by chi-squared test, Kaplan-Meier survival curve, and Cox regression analysis. Results: Of 154 patients, 35 exhibited disease progression or recurrence. ROC analysis revealed that baseline 18F-FDG PET/CT metabolic parameters, including maximum standardized uptake value (SUVmax0), total metabolic tumor volume (TMTV0), standardized total metabolic tumor volume (STMTV0), and the distance between the two furthest lesions (Dmax), along with interim 18F-FDG PET/CT metabolic parameters such as total tumor lesion glycolysis (TTLG1), SUVmax1, TMTV1, and the rate of change of SUVmax (%ΔSUVmax), were predictive of relapse or progression in DLBCL patients (P < 0.05). The chi-squared test showed that TMTV0, STMTV0, Dmax, SUVmax1, TMTV1, TTLG1, %ΔSUVmax, Deauville score, IPI, Ann Arbor stage, and LDH were associated with patient prognosis (P < 0.05). Multivariate Cox regression analysis showed that Dmax (P = 0.021) and %ΔSUVmax (P = 0.030) were independent predictors of prognosis in DLBCL patients. There were statistically significant differences in PFS among the three groups with high, intermediate, and low risk according to the combination model (P < 0.001). The combination model presented higher predictive efficacy than single indicators. Conclusion: The combined model of baseline parameter Dmax and intermediate parameter %ΔSUVmax of 18F-FDG PET/CT improved the predictive efficacy of PFS and contributed to the risk stratification of patients, providing a reference for clinical individualization and precision treatment. [ABSTRACT FROM AUTHOR]

Background: Although recent guidelines advocate for HbA1c target individualization, a comprehensive criterion for patient categorization remains absent. This study aimed to categorize HbA1c variability levels and explore the relationship between glycemic control, cardiovascular outcomes, and mortality across different degrees of variability. Methods: Action to Control Cardiovascular Risk in Diabetes study data were used. HbA1c variability was measured using the HbA1c variability score (HVS) and standard deviation (SD). K-means and K-medians clustering were used to combine the HVS and SD. Results: K-means clustering was the most stable algorithm with the lowest clustering similarities. In the low variability group, intensive glucose-lowering treatment significantly reduced the risk of adverse cardiovascular outcomes (HR: 0·78 [95% CI: 0·63, 0·97]) without increasing mortality risk (HR: 1·07 [0.81, 1·42]); the risk of adverse cardiovascular events (HR: 1·33 [1·14, 1·56]) and all-cause mortality (HR: 1·23 [1·01,1·51]) increased with increasing mean HbA1c. In the high variability group, treatment increased the risk of cardiovascular events (HR: 2.00 [1·54, 2·60]) and mortality (HR: 2·20 [1·66, 2·92]); a higher mean HbA1c (7·86%, [7·66%, 8·06%]) had the lowest mortality risk, when the mean HbA1c was < 7·86%, a higher mean HbA1c was associated with a lower mortality risk (HR: 0·63 [0·42, 0·95]). In the medium variability group, a mean HbA1c around 7·5% was associated with the lowest risk. Conclusions: HbA1c variability can guide glycemic control targets for patients with type 2 diabetes. For patients with low variability, the lower the HbA1c, the lower the risk. For those with medium variability, controlling HbA1c at 7·5% provides the maximum benefit. For patients with high variability, a mean HbA1c of around 7·8% presents the lowest risk of all-cause mortality, a lower HbA1c did not provide cardiovascular benefits but instead increased the mortality risk. Further studies, especially those with patients that reflect the general population with type 2 diabetes undergoing the latest therapeutic approaches, are essential to validate the conclusions of this study. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to develop and refine the content and design of an internet-based support and education program for patients awaiting kidney transplantation from deceased donors. Design: A Delphi process was used. Methods: A prototype internet-based intervention was drafted, based on previous research. The intervention included educational and psychological support to manage the uncertain waiting time and specific education enabling preparation for transplantation and adjustment to life after transplantation. In a two-round Delphi process, patients who had received a kidney transplant from a deceased donor within the last 2 years (n = 27), significant others (n = 6), health-care personnel with renal (n = 20) or transplant (n = 14) expertise, rated importance of content and design aspects of the prototype intervention on a 5-point scale using web questionnaires. A median of ≥ 3 was considered as consensus. Quantitative data was analyzed using descriptive statistics. Free text answers were encouraged and analyzed using deductive content analysis. The STROBE-checklist was used. Results: Consensus was reached for all suggested content and design items in round 1, with median ratings of 4 or 5. Qualitative analysis from round 1 suggested four new content and design items which were rated in round 2, on all which consensus was reached; information about life with young children as relatives, expansion of kidney transplantation specific information, program extension by one week and individualization by making information available based on individual needs. Conclusion: There was consensus among heterogenous experts regarding suggested educational and psychological support content and design aspects, and additional content and design aspects were identified for an internet-based support and education program for patients awaiting kidney transplantation from deceased donors. [ABSTRACT FROM AUTHOR]

Background: Information about the achievement of glycemic targets in patients with type 2 diabetes according to different individualization strategies is scarce. Our aim was to analyze the allocation of type 2 diabetic patients into individualized glycemic targets according to different strategies of individualization and to assess the degree of achievement of adequate control. Methods: Cross-sectional analysis on 5382 type 2 diabetic patients in primary care setting in Spain between 2011 and 2012. Targets of HbA1c were assigned based on different strategies of individualization of glycemic targets: 1) the ADA/EASD consensus 2) The Spanish Diabetes Society (SED) consensus 3) a strategy that accounts for the risk of hypoglycemia (HYPO) considering the presence of a hypoglycemia during the last year and type of hypoglycemic treatment. Concordance between the different strategies was analyzed. Results: A total of 15.9, 17.1 and 67 % applied to ADA/EASD recommendation of HbA1c target of <6.5, < 7 and <8 % (48, 53 and 64 mmol/mol), and 31.9 and 67.4 % applied to the SED glycemic target of <6.5 and <7.5 % (<48 and 58 mmol/mol). Using the HYPO strategy, 53.5 % had a recommended HbA1c target <7 % (53 mmol/mol). There is a 94 % concordance between the ADA/EASD and SED strategies, and a concordance of 41-42 % between these strategies and HYPO strategy. Using the three different strategies, the overall proportion of patients achieving glycemic targets was 56-68 %. Conclusions: Individualization of glycemic targets increases the number of patients who are considered adequately controlled. The proposed HYPO strategy identifies a similar proportion of patients that achieve adequate glycemic control than ADA/EASD or SED strategies, but its concordance with these strategies in terms of patient classification is bad. [ABSTRACT FROM AUTHOR]

The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is happening in the microcirculation of organs, which prevents them from achieving an additional degree of individualization of the hemodynamic resuscitation at tissue level. Indeed, clinicians never know whether optimization of the microcirculation and tissue oxygenation is actually achieved after macrovascular hemodynamic optimization. The challenge for the future is to have noninvasive, easy-to-use equipment that allows reliable assessment and immediate quantitative analysis of the microcirculation at the bedside. There are different methods for assessing the microcirculation at the bedside; all have strengths and challenges. The use of automated analysis and the future possibility of introducing artificial intelligence into analysis software could eliminate observer bias and provide guidance on microvascular-targeted treatment options. In addition, to gain caregiver confidence and support for the need to monitor the microcirculation, it is necessary to demonstrate that incorporating microcirculation analysis into the reasoning guiding hemodynamic resuscitation prevents organ dysfunction and improves the outcome of critically ill patients. [ABSTRACT FROM AUTHOR]

Background: The development of drug resistance and high mortality rates are the major problems observed in non-small cell lung cancer (NSCLC). Biomarkers indicating and predicting disease development towards these unfavorable directions are therefore on high demand. Many studies have demonstrated that changes in miRNAs expression may be associated with a response to treatment and disease prognosis, thus suggesting its potential biomarker value for a broad spectrum of clinical applications. The aim of the present study was to investigate the expression level of miR-181a-5p, miR-630, and its targets in NSCLC tumor tissue and plasma samples; and to analyze its association with NSCLC patient’s response to treatment and disease prognosis. Methods: The study was performed in 89 paired tissue specimens and plasma samples obtained from NSCLC patients who underwent surgical treatment at the Department of Thoracic Surgery and Oncology of the National Cancer Institute. Analysis of miR-181a-5p and miR-630 expression was performed by qRT-PCR using TaqMan miRNA specific primers. Whereas BCL2, LMO3, PTEN, SNAI2, WIF1 expression levels were identified with KAPA SYBR FAST qPCR Kit. Each sample was examined in triplicate and calculated following the 2-ΔΔCt method. When the p-value was less than 0.05, the differences were considered statistically significant. Results: It was found that miR-181a-5p and miR-630 expression levels in NSCLC tissue and plasma samples were significantly decreased compared with control samples. Moreover, patients with low miR-181a-5p expression in tumor tissue and plasma had longer PFS rates than those with high miRNA expression. Decreased miR-630 expression in tumor was statistically significantly associated with better NSCLC patients’ OS. In addition, the expression of miR-181a-5p, as well as miR-630 in tumor tissue, are the statistically significant variables for NSCLC patients’ OS. Moreover, in NSCLC patient plasma samples circulating miR-181a-5p can be evaluated as significant independent prognostic factors for OS and PFS. Conclusions: Our findings indicate the miR-181a-5p and miR-630 expression levels have the potential to prognose and predict and therefore improve the treatment individualization and the outcome of NSCLC patients. Circulating miR-181a-5p has the potential clinical value as a non-invasive biomarker for NSCLC. [ABSTRACT FROM AUTHOR]

Abnormal retro patellar stress is believed to contribute to patellofemoral complications after total knee arthroplasty (TKA), but the causal link between TKA and patellofemoral contact stress remains unclear. By reviewing the relevant studies, we found that both TKA implantation and additional patellar resurfacing increase retro patellar pressure. The rotation and size of the femoral component, thickness and position of the patellar component, installation of the tibial component, prosthesis design and soft tissue balance further influence patellofemoral stress. Specific measures can be applied to reduce stress, including the installation of the femoral prosthesis with an appropriate external rotation angle, placing the tibial component at a more posterior position and the patellar button at a more medial position, avoiding over-sized femoral and patellar components, selecting posterior-stabilized design rather than cruciate-retaining design, using gender-specific prosthesis or mobile-bearing TKA system, and releasing the lateral retinaculum or performing partial lateral facetectomy. Despite these measures, the principle of individualization should be followed to optimize the patellofemoral biomechanics. [ABSTRACT FROM AUTHOR]

Background: Older adults with frailty are at an increased risk of adverse outcomes after surgery. Exercise before surgery (exercise prehabilitation) may reduce adverse events and improve recovery after surgery. However, adherence with exercise therapy is often low, especially in older populations. The purpose of this study was to qualitatively assess the barriers and facilitators to participating in exercise prehabilitation from the perspective of older people with frailty participating in the intervention arm of a randomized trial. Methods: This was a research ethics approved, nested descriptive qualitative study within a randomized controlled trial of home-based exercise prehabilitation vs. standard care with older patients (≥ 60 years) having elective cancer surgery, and who were living with frailty (Clinical Frailty Scale ≥ 4). The intervention was a home-based prehabilitation program for at least 3 weeks before surgery that involved aerobic activity, strength and stretching, and nutritional advice. After completing the prehabilitation program, participants were asked to partake in a semi-structured interview informed by the Theoretical Domains Framework (TDF). Qualitative analysis was guided by the TDF. Results: Fifteen qualitative interviews were completed. Facilitators included: 1) the program being manageable and suitable to older adults with frailty, 2) adequate resources to support engagement, 3) support from others, 4) a sense of control, intrinsic value, noticing progress and improving health outcomes and 5) the program was enjoyable and facilitated by previous experience. Barriers included: 1) pre-existing conditions, fatigue and baseline fitness, 2) weather, and 3) guilt and frustration when unable to exercise. A need for individualization and variety was offered as a suggestion by participants and was therefore described as both a barrier and facilitator. Conclusions: Home-based exercise prehabilitation is feasible and acceptable to older people with frailty preparing for cancer surgery. Participants identified that a home-based program was manageable, easy to follow with helpful resources, included valuable support from the research team, and they reported self-perceived health benefits and a sense of control over their health. Future studies and implementation should consider increased personalization based on health and fitness, psychosocial support and modifications to aerobic exercises in response to adverse weather conditions. [ABSTRACT FROM AUTHOR]

Background: Sexual dimorphism is obvious not only in the overall architecture of human body, but also in intraoral details. Many studies have found a correlation between gender and morphometric features of teeth, such as mesio-distal diameter, buccal-lingual diameter and height. However, it's still difficult to detect gender through the observation of intraoral photographs, with accuracy around 50%. The purpose of this study was to explore the possibility of automatically telling gender from intraoral photographs by deep neural network, and to provide a novel angle for individual oral treatment. Methods: A deep learning model based on R-net was proposed, using the largest dataset (10,000 intraoral images) to support the automatic detection of gender. In order to reverse analyze the classification basis of neural network, Gradient-weighted Class Activation Mapping (Grad-CAM) was used in the second step, exploring anatomical factors associated with gender recognizability. The simulated modification of images based on features suggested was then conducted to verify the importance of characteristics between two genders. Precision (specificity), recall (sensitivity) and receiver operating characteristic (ROC) curves were used to evaluate the performance of our network. Chi-square test was used to evaluate intergroup difference. A value of p < 0.05 was considered statistically significant. Results: The deep learning model showed a strong ability to learn features from intraoral images compared with human experts, with an accuracy of 86.5% and 82.5% in uncropped image data group and cropped image data group respectively. Compared with hard tissue exposed in the mouth, gender difference in areas covered by soft tissue was easier to identify, and more significant in mandibular region than in maxillary region. For photographs with simulated removal of lips and basal bone along with overlapping gingiva, mandibular anterior teeth had similar importance for sex determination as maxillary anterior teeth. Conclusions: Deep learning method could detect gender from intraoral photographs with high efficiency and accuracy. With assistance of Grad-CAM, the classification basis of neural network was deciphered, which provided a more precise entry point for individualization of prosthodontic, periodontal and orthodontic treatments. [ABSTRACT FROM AUTHOR]

Backgrounds: Cardiopulmonary resuscitation (CPR) training is generally led by instructors in a classroom; thus, conventional teaching materials used in CPR training are often constrained by spatiotemporal factors, limiting learners' interest and sense of achievement in learning and preventing them from effectively applying what they learn in practice. For greater effectiveness and more flexible application, clinical nursing education has increasingly emphasized contextualization, individualization, and interprofessional learning. This study determined the self-assessed emergency care competencies of nurses who received gamified emergency care training and explored the factors associated with those competencies. Methods: Quota sampling of nurses working at a certain regional hospital in central Taiwan was conducted, and a structured questionnaire was administered to the recruited nurses. A total of 194 valid responses were collected. The research tool was a scale measuring the participants' emergency care competencies after they received gamified emergency care training. The data were analyzed using descriptive and inferential statistics and multiple regression. Results: Of the recruited participants, 50.52% were ≤ 30 years old; 48.45% worked in the internal medicine department; 54.64% graduated from 2-year university technical programs; 54.12% were N2 registered nurses; 35.57% and 21.13% had ≥ 10 and 1–3 years of work experience, respectively; and 48.45% worked in general wards. User need (r = 0.52, p = 0.000), perceived usefulness (r = 0.54, p = 0.000), perceived ease of use (r = 0.51, p = 0.000), and usage attitude (r = 0.41, p = 0.000) were positively correlated with emergency care competencies. Furthermore, the multiple regression analysis revealed that perceived usefulness was the primary factor associated with the participants' emergency care competencies. Conclusions: The results of this study may serve as a reference for acute care facility authorities in designing advanced nursing competency standards and emergency care training programs for nurses. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes cluster in lower social groups and people with type 2 diabetes from lower social groups experience more complications, benefit less from health services and live shorter lives than people with type 2 diabetes from higher social groups. Different logics govern diabetes care and potentially influence the possibility of socially vulnerable type 2 diabetes patients to access and benefit from health services. In order to understand which practice and underlying logic enable socially vulnerable type 2 diabetes patients to access and benefit from diabetes care we aim to describe what professionals at a specialized diabetes clinic do to adjust services to patient's needs and make the tasks involved in diabetes care doable for socially vulnerable patients and how this work is embedded in an organizational and moral context.Methods: Ethnographic fieldwork combining participant observation and interviews was carried out between February 2017 and March 2018 in a specialized diabetes clinic located in a socially deprived area in the capital region of Denmark. Sixteen patients (9 male, 7 female, aged 35-73 years) and 12 professionals (7 doctors, 4 nurses, 1 secretary) participated in the study. We used Annemarie Mol's concept of "the logic of care" to guide our analysis.Results: Our analysis shows that the logic of care and the care practices in this clinic are characterized by a needs-based approach to treatment involving adjustment of services (permeability, timing, and content) and seeing the patient as a person with many needs. Throughout our description of selected care practices, we both characterize how health professionals practice this particular logic of care and the organizational and normative conditions that this logic is entangled with.Conclusions: Practicing diabetes care based on patients' needs involves individualization, something often described as an element of patient centred care. Our study shows that this ideal of individualization and adjustment of treatment is possible in practice. Organizational flexibility and an organizational culture that values patient needs enable needs-based care. In order for socially vulnerable type 2 diabetes patients to benefit from health services it is necessary to create conditions under which professionals can attend to these patients' multiple and complex needs. Adjusting care to these needs demand a variety of professional efforts some of which are hardly predictable or standardisable. [ABSTRACT FROM AUTHOR]

Backgrounds: Despite publication of international guidelines, there are notable controversial points of clinical target volume (CTV) delineation in nasopharyngeal carcinoma (NPC). Recently, scholars proposed a novel way of delineation of CTV in NPC—individualization of CTV delineation based on T classification and spread patterns, which yielded excellent long-term local control with limited late toxicities. The aim of this study was to clarify the anatomic patterns and pathways of local recurrence of NPC and provide a clinical reference for the delineation of CTV. Methods: A total of 869 patients with non-metastatic NPC were treated with intensity-modulated radiation therapy (IMRT) at our institution between 2009 and 2010. Among the 57 cases of local/locoregional recurrence, 52 cases with traceable radiotherapy plans and magnetic resonance imaging at the time of the first diagnosis of recurrence were included. Anatomical structures and gross tumor volume of local recurrence were contoured. The incidence of relapse of each anatomic structure, route of local recurrence, and their correlation were analyzed. Results: Locally advanced disease had a significantly increased risk of recurrence in the posterior nasal cavity and a trend towards higher risk of recurrence in the clivus, lateral pterygoid muscle, and hypoglossal canal. Based on the incidence of local recurrence, we constructed a high-risk map for the early and locally advanced stages. Local recurrences were classified into five routes, where anterior extension accounted for the majority (30.8%), and caudal tumor extension pathway had the lowest incidence (5.8%). There was a significant correlation between the local recurrences of neural foramina and neighboring anatomical structures along each pathway. All cases relapsed at unilateral cavernous sinus, most at the same side of primary tumor. Based on our findings, we proposed some suggestions on delineations of CTV, based on T classification and local extension pattern. Conclusions: Local recurrence of NPC varied according to T classification, followed a stepwise pattern, spread via neural foramina, and recurred at ipsilateral cavernous sinus. This provides meaningful clinical evidence for delineation of CTV, especially individualized delineation. [ABSTRACT FROM AUTHOR]

Acute respiratory failure (ARF) is defined by acute and progressive hypoxemia caused by various cardiorespiratory or systemic diseases in previously healthy patients. Among ARF, acute respiratory distress syndrome (ARDS) is a serious condition with bilateral lung infiltration, which develops secondary to a variety of underlying conditions, diseases, or injuries. This review summarizes the current standard of care for ARF and ARDS based on current major guidelines in this field. When administering fluid in patients with ARF, particularly ARDS, restrictive strategies need to be considered in patients without shock or multiple organ dysfunction. Regarding oxygenation targets, avoiding excessive hyperoxemia and hypoxemia is probably a reasonable choice. As a result of the rapid spread and accumulation of evidence for high-flow nasal cannula oxygenation, it is now weakly recommended for the respiratory management of ARF in general and even for initial management of ARDS. Noninvasive positive pressure ventilation is also weakly recommended for the management of certain ARF conditions and as initial management of ARDS. Low tidal volume ventilation is now weakly recommended for all patients with ARF and strongly recommended for patients with ARDS. Limiting plateau pressure and high-level PEEP are weakly recommended for moderate-to-severe ARDS. Prone position ventilation with prolonged hours is weakly to strongly recommended for moderate-to-severe ARDS. In patients with COVID-19, ventilatory management is essentially the same as for ARF and ARDS, but awake prone positioning may be considered. In addition to standard care, treatment optimization and individualization, as well as the introduction of exploratory treatment, should be considered as appropriate. As a single pathogen, such as SARS-CoV-2, exhibits a wide variety of pathologies and lung dysfunction, ventilatory management for ARF and ARDS may be better tailored according to the respiratory physiologic status of individual patients rather than the causal or underlying diseases and conditions. [ABSTRACT FROM AUTHOR]

Background : One-third of the community-dwelling older persons fall annually. Guidelines recommend the use of multifactorial falls prevention interventions. However, these interventions are difficult to implement into the community. This systematic review aimed to explore strategies used to implement multifactorial falls prevention interventions into the community. Methods: A systematic search in PubMed (including MEDLINE), CINAHL (EBSCO), Embase, Web of Science (core collection), and Cochrane Library was performed and updated on the 25th of August, 2022. Studies reporting on the evaluation of implementation strategies for multifactorial falls prevention interventions in the community setting were included. Two reviewers independently performed the search, screening, data extraction, and synthesis process (PRISMA flow diagram). The quality of the included reports was appraised by means of a sensitivity analysis, assessing the relevance to the research question and the methodological quality (Mixed Method Appraisal Tool). Implementation strategies were reported according to Proctor et al.'s (2013) guideline for specifying and reporting implementation strategies and the Taxonomy of Behavioral Change Methods of Kok et al. (2016). Results: Twenty-three reports (eighteen studies) met the inclusion criteria, of which fourteen reports scored high and nine moderate on the sensitivity analysis. All studies combined implementation strategies, addressing different determinants. The most frequently used implementation strategies at individual level were "tailoring," "active learning," "personalize risk," "individualization," "consciousness raising," and "participation." At environmental level, the most often described strategies were "technical assistance," "use of lay health workers, peer education," "increasing stakeholder influence," and "forming coalitions." The included studies did not describe the implementation strategies in detail, and a variety of labels for implementation strategies were used. Twelve studies used implementation theories, models, and frameworks; no studies described neither the use of a determinant framework nor how the implementation strategy targeted influencing factors. Conclusions: This review highlights gaps in the detailed description of implementation strategies and the effective use of implementation frameworks, models, and theories. The review found that studies mainly focused on implementation strategies at the level of the older person and healthcare professional, emphasizing the importance of "tailoring," "consciousness raising," and "participation" in the implementation process. Studies describing implementation strategies at the level of the organization, community, and policy/society show that "technical assistance," "actively involving stakeholders," and "forming coalitions" are important strategies. Trial registration: PROSPERO CRD42020187450 [ABSTRACT FROM AUTHOR]

Introduction: For individuals diagnosed with diabetes mellitus, the practice of properly oriented physical exercises brings significant benefits to the individual's health and is considered an indispensable tool for metabolic management. The individualization of exercise routines is an essential aspect for therapeutic success, despite the need to consider some general recommendations. This review is an authorized literal translation of the Brazilian Society of Diabetes (SBD) Guidelines 2021–2022, which is based on scientific evidence and provides guidance on physical activities and exercises aimed at individuals with type 1 and 2 diabetes. Methods: SBD designated 9 specialists from its “Department of Diabetes, Exercise & Sports” to author chapters on physical activities and exercises directed to individuals with type 1 and 2 diabetes. The aim of these chapters was to highlight recommendations in accordance with Evidence Levels, based on what is described in the literature. These chapters were analyzed by the SBD Central Committee, which is also responsible for the SBD 2021–2022 guidelines. Main clinical inquiries were selected to perform a narrated review by using MEDLINE via PubMed. Top available evidence, such as high-quality clinical trials, large observational studies and meta-analyses related to physical activity and exercise advisory, were analyzed. The adopted MeSh terms were [diabetes], [type 1 diabetes], [type 2 diabetes], [physical activity] [physical exercise]. Results: 17 recommendations were defined by the members. For this review, it was considered different Evidence Levels, as well as different Classes of Recommendations. As to Evidence Levels, the following levels were contemplated: Level A) More than one randomized clinical trial or a randomized clinical trial meta-analysis with low heterogeneity. Level B) Meta analysis with observational studies, one randomized clinical trial, sizeable observational studies and sub-groups analysis. Level C) Small non-randomized studies, cross-sectional studies, case control studies, guidelines or experts’ opinions. In respect to Recommendation Classes, the following criteria were adopted: I. “Recommended”: Meaning there was a consent of more than 90% of the panel; IIa. “Must be considered”: meaning there is a general preference of the panel which 70–90% agrees; IIb. “Can be considered”. 50–70% agrees; III Not recommended: There is a consensus that the intervention should not be performed. Conclusion: Physical exercise aids on the glycemic control of type 2 diabetes individuals while also decreasing cardiovascular risk in individuals with type 1 and 2 diabetes. Individuals diagnosed with diabetes should perform combined aerobic and resistance exercises in order to manage the disease. In addition, exercises focusing on flexibility and balance should be specially addressed on elderly individuals. Diabetes individuals using insulin as therapeutic treatment should properly monitor glycemia levels before, during and after exercise sessions to minimize health incidents, such as hypoglycemia. [ABSTRACT FROM AUTHOR]

Background: Betamethasone (BMZ) is used to accelerate fetal lung maturation in women with threatened preterm birth, but its efficacy is variable and limited by the lack of patient individualization in its dosing and administration. To determine sources of variability and potential opportunities for individualization of therapy, the objective of this study was to evaluate maternal factors associated with development of neonatal respiratory distress syndrome (RDS) in a cohort of women who received betamethasone.Methods: This study prospectively enrolled women, gestational ages 23-34 weeks, who received betamethasone for threatened preterm birth. Maternal demographics, prenatal history, and neonatal outcomes were abstracted from hospital records. RDS was the primary outcome. Associations between RDS diagnosis and maternal demographics, prenatal history, and betamethasone dosing were evaluated in a case-control analysis and multivariable regression adjusted for gestational age at delivery. Secondary analyses limited the cohort to women who delivered within 1 or 2 weeks of betamethasone dosing.Results: Of 209 deliveries, 90 (43 %) resulted in neonatal RDS. Within the overall cohort and controlling for gestational age at birth, RDS was only associated with cesarean births compared to vaginal births (adjusted OR 1.17 [1.06-1.29]). Route of delivery was also the only significant factor related to RDS in the 83 neonates delivered within 7 days of BMZ dosing. However, among 101 deliveries within 14 days of betamethasone dosing and controlling for gestational age at birth, women who experienced preterm premature rupture of membranes (PPROM) had lower RDS rates than those without PPROM (57.9 % vs. 80.2 %, adjusted OR 0.81 [0.67-0.99]). Maternal age, BMI, race, and ethnicity were not associated with RDS in the regression models.Conclusions: Of maternal characteristics analyzed, only delivery by cesarean was associated with neonatal RDS after antenatal betamethasone use. [ABSTRACT FROM AUTHOR]

Background: Individualization of the follicle-stimulating hormone (FSH) starting dose is considered standard clinical practice during controlled ovarian stimulation (COS) in patients undergoing assisted reproductive technology (ART) treatment. Furthermore, the gonadotropin dose is regularly adjusted during COS to avoid hyper- or hypo-ovarian response, but limited data are currently available to characterize such adjustments. This review describes the frequency and direction (increase/decrease) of recombinant-human FSH (r-hFSH) dose adjustment reported in clinical trials. Methods: We evaluated the proportion of patients undergoing ART treatment who received ≥ 1 r-hFSH dose adjustments. The inclusion criteria included studies (published Sept 2007 to Sept 2017) in women receiving ART treatment that allowed dose adjustment within the study protocol and that reported ≥ 1 dose adjustments of r-hFSH; studies not allowing/reporting dose adjustment were excluded. Data on study design, dose adjustment and patient characteristics were extracted. Point-incidence estimates were calculated per study and overall based on pooled number of cycles with dose adjustment across studies. The Clopper–Pearson method was used to calculate 95% confidence intervals (CI) for incidence where adjustment occurred in < 10% of patients; otherwise, a normal approximation method was used. Results: Initially, 1409 publications were identified, of which 318 were excluded during initial screening and 1073 were excluded after full text review for not meeting the inclusion criteria. Eighteen studies (6630 cycles) reported dose adjustment: 5/18 studies (1359 cycles) reported data for an unspecified dose adjustment (direction not defined), in 10/18 studies (3952 cycles) dose increases were reported, and in 11/18 studies (5123 cycles) dose decreases were reported. The studies were performed in women with poor, normal and high response, with one study reporting in oocyte donors and one in obese women. The median day that dose adjustment was permitted was Day 6 after the start of treatment. The point estimates for incidence (95% CI) for unspecified dose adjustment, dose increases, and dose decreases were 45.3% (42.7, 48.0), 19.2% (18.0, 20.5), and 9.5% (8.7, 10.3), respectively. Conclusions: This systematic review highlights that, in studies in which dose adjustment was allowed and reported, the estimated incidence of r-hFSH dose adjustments during ovarian stimulation was up to 45%. [ABSTRACT FROM AUTHOR]

Background: Interventions in which individual older patients with multi-morbidity participate in formulating goals for their own care are being implemented in several countries. Successful service delivery requires normative integration by which values and goals for the intervention are shared between actors at macro-, meso- and micro-levels of health services. However, health services are influenced by multiple and different institutional logics, which are belief systems guiding actors' cognitions and practices. This paper examines how distinct institutional logics materialize in justifications for patient participation within an intervention for patients with multi-morbidity, focusing on how variations in the institutional logics that prevail at different levels of health services affect vertical normative integration.Methods: This qualitative case study of normative integration spans three levels of Norwegian health services. The macro-level includes a white paper and a guideline which initiated the intervention. The meso-level includes strategy plans and intervention tools developed locally in four municipalities. Finally, the micro-level includes four focus group discussions among 24 health professionals and direct observations of ten care-planning meetings between health professionals and patients. The content analysis draws on seven institutional logics: professional, market, family, community, religious, state and corporate.Results: The particular institutional logics that justified patient participation varied between healthcare levels. Within the macro-level documents, seven logics justified patients' freedom of choice and individualization of service delivery. At meso-level, the operationalization of the intervention into tools for clinical practice was dominated by a state logic valuing equal services for all patients and a medical professional logic in which patient participation meant deciding how to maintain patients' physical abilities. At micro-level, these two logics were mixed with a corporate logic prioritizing cost-efficient service delivery.Conclusion: Normative integration is challenging to achieve. The number of institutional logics in play was reduced downwards through the three levels, and the goals behind the intervention shifted from individualization to standardization. The study broadens our understanding of the dynamic between institutional logics and of how multiple sets of norms co-exist and guide action. Knowledge of mechanisms by which normative justifications are put into practice is important to achieve normative integration of patient participation interventions. [ABSTRACT FROM AUTHOR]

Background: High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer. Although most patients will initially respond to first-line treatment with a combination of surgery and platinum-based chemotherapy, up to a quarter will be resistant to treatment. We aimed to identify a new strategy to improve HGSC patient management at the time of cancer diagnosis (HGSC-1LTR). Methods: A total of 109 ready-available formalin-fixed paraffin-embedded HGSC tissues obtained at the time of HGSC diagnosis were selected for proteomic analysis. Clinical data, treatment approach and outcomes were collected for all patients. An initial discovery cohort (n = 21) were divided into chemoresistant and chemosensitive groups and evaluated using discovery mass-spectrometry (MS)-based proteomics. Proteins showing differential abundance between groups were verified in a verification cohort (n = 88) using targeted MS-based proteomics. A logistic regression model was used to select those proteins able to correctly classify patients into chemoresistant and chemosensitive. The classification performance of the protein and clinical data combinations were assessed through the generation of receiver operating characteristic (ROC) curves. Results: Using the HGSC-1LTR strategy we have identified a molecular signature (TKT, LAMC1 and FUCO) that combined with ready available clinical data (patients' age, menopausal status, serum CA125 levels, and treatment approach) is able to predict patient response to first-line treatment with an AUC: 0.82 (95% CI 0.72–0.92). Conclusions: We have established a new strategy that combines molecular and clinical parameters to predict the response to first-line treatment in HGSC patients (HGSC-1LTR). This strategy can allow the identification of chemoresistance at the time of diagnosis providing the optimization of therapeutic decision making and the evaluation of alternative treatment strategies. Thus, advancing towards the improvement of patient outcome and the individualization of HGSC patients' care. [ABSTRACT FROM AUTHOR]

Background: Oxygen is one of the most commonly used drugs by anesthesiologists. The World Health Organization (WHO) gave recommendations regarding perioperative oxygen administration, but the practice of oxygen use in anesthesia, critical emergency, and intensive care medicine remains unclear. Methods: We conducted an online survey among members of the European Society of Anaesthesiology and Intensive Care (ESAIC). The questionnaire consisted of 46 queries appraising the perioperative period, emergency medicine and in the intensive care, knowledge about current recommendations by the WHO, oxygen toxicity, and devices for supplemental oxygen therapy. Results: Seven hundred ninety-eight ESAIC members (2.1% of all ESAIC members) completed the survey. Most respondents were board-certified and worked in hospitals with > 500 beds. The majority affirmed that they do not use specific protocols for oxygen administration. WHO recommendations are unknown to 42% of respondents, known but not followed by 14%, and known and followed by 24% of them. Respondents prefer inspiratory oxygen fraction (FiO2) ≥80% during induction and emergence from anesthesia, but intraoperatively < 60% for maintenance, and higher FiO2 in patients with diseased than non-diseased lungs. Postoperative oxygen therapy is prescribed more commonly according to peripheral oxygen saturation (SpO2), but shortage of devices still limits monitoring. When monitoring is used, SpO2 ≤ 95% is often targeted. In critical emergency medicine, oxygen is used frequently in patients aged ≥80 years, or presenting with respiratory distress, chronic obstructive pulmonary disease, myocardial infarction, and stroke. In the intensive care unit, oxygen is mostly targeted at 96%, especially in patients with pulmonary diseases. Conclusions: The current practice of perioperative oxygen therapy among respondents does not follow WHO recommendations or current evidence, and access to postoperative monitoring devices impairs the individualization of oxygen therapy. Further research and additional teaching about use of oxygen are necessary. [ABSTRACT FROM AUTHOR]

Background: Renal replacement therapy (RRT) remains the key rescue therapy for critically ill patients with severe acute kidney injury (AKI). However, there are currently no tools available to predict successful liberation from RRT. Biomarkers may allow for risk stratification and individualization of treatment strategies. Proenkephalin A 119-159 (penKid) has been suggested as a promising marker of kidney function in the context of AKI, but has not yet been evaluated for RRT liberation in critically ill patients with AKI.Methods: This post hoc analysis included 210 patients from the randomized clinical ELAIN trial and penKid levels were measured in the blood of these patients. Competing risk time-to-event analyses were performed for pre-RRT penKid at initiation of RRT and in a landmark analysis at day 3 after initiation of RRT. Competing risk endpoints were successful liberation from RRT or death without prior liberation from RRT.Results: Low pre-RRT penKid levels (penKid ≤ 89 pmol/l) at RRT initiation were associated with early and successful liberation from RRT compared to patients with high pre-RRT penKid levels (subdistribution hazard ratio (sHR) 1.83, 95%CI 1.26-2.67, p = 0.002, estimated 28d-cumulative incidence function (28d-CIF) of successful liberation from RRT 61% vs. 45%, p = 0.022). This association persisted in the landmark analysis on day 3 of RRT (sHR 1.78, 95%CI 1.17-2.71, p = 0.007, 28d-CIF of successful liberation from RRT 67% vs. 47%, p = 0.018). For both time points, no difference in the competing event of death was detected.Conclusions: In critically ill patients with RRT-dependent AKI, plasma penKid appears to be a useful biomarker for the prediction of shorter duration and successful liberation from RRT and may allow an individualized approach to guide strategies of RRT liberation in critically ill patients with RRT-dependent AKI.Trial Registration: The ELAIN trial was prospectively registered at the German Clinical Trial Registry (Identifier: DRKS00004367) on 28th of May 2013. [ABSTRACT FROM AUTHOR]

Background: Mechanical ventilation increases the risk of lung injury (VILI). Some authors propose that the way to reduce VILI is to find the threshold of driving pressure below which VILI is minimized. In this study, we propose a method to titrate the driving pressure to pulmonary elastance in an acute respiratory distress syndrome model using Young's modulus and its consequences on ventilatory-induced lung injury.Material and Methods: 20 Wistar Han male rats were used. After generating an acute respiratory distress syndrome, two groups were studied: (a) standard protective mechanical ventilation: 10 rats received 150 min of mechanical ventilation with driving pressure = 14 cm H2O, tidal volume < 6 mL/kg) and (b) individualized mechanical ventilation: 10 rats received 150 min of mechanical ventilation with an individualized driving pressure according to their Young's modulus. In both groups, an individualized PEEP was programmed in the same manner. We analyzed the concentration of IL-6, TNF-α, and IL-1ß in BAL and the acute lung injury score in lung tissue postmortem.Results: Global driving pressure was different between the groups (14 vs 11 cm H2O, p = 0.03). The individualized mechanical ventilation group had lower concentrations in bronchoalveolar lavage of IL-6 (270 pg/mL vs 155 pg/mL, p = 0.02), TNF-α (292 pg/mL vs 139 pg/mL, p < 0.01) and IL-1ß (563 pg/mL vs 131 pg/mL, p = 0.05). They presented lower proportion of lymphocytes (96% vs 79%, p = 0.05) as well as lower lung injury score (6.0 points vs 2.0 points, p = 0.02).Conclusion: In our model, individualization of DP to pulmonary elastance through Young's modulus decreases lung inflammation and structural lung injury without a significant impact on oxygenation. [ABSTRACT FROM AUTHOR]

Background: Evidence to guide type 2 diabetes treatment individualization is limited. We evaluated heterogeneous treatment effects (HTE) of intensive glycemic control in type 2 diabetes patients on major adverse cardiovascular events (MACE) in the Action to Control Cardiovascular Risk in Diabetes Study (ACCORD) and the Veterans Affairs Diabetes Trial (VADT). Methods: Causal forests machine learning analysis was performed using pooled individual data from two randomized trials (n = 12,042) to identify HTE of intensive versus standard glycemic control on MACE in patients with type 2 diabetes. We used variable prioritization from causal forests to build a summary decision tree and examined the risk difference of MACE between treatment arms in the resulting subgroups. Results: A summary decision tree used five variables (hemoglobin glycation index, estimated glomerular filtration rate, fasting glucose, age, and body mass index) to define eight subgroups in which risk differences of MACE ranged from − 5.1% (95% CI − 8.7, − 1.5) to 3.1% (95% CI 0.2, 6.0) (negative values represent lower MACE associated with intensive glycemic control). Intensive glycemic control was associated with lower MACE in pooled study data in subgroups with low (− 4.2% [95% CI − 8.1, − 1.0]), intermediate (− 5.1% [95% CI − 8.7, − 1.5]), and high (− 4.3% [95% CI − 7.7, − 1.0]) MACE rates with consistent directions of effect in ACCORD and VADT alone. Conclusions: This data-driven analysis provides evidence supporting the diabetes treatment guideline recommendation of intensive glucose lowering in diabetes patients with low cardiovascular risk and additionally suggests potential benefits of intensive glycemic control in some individuals at higher cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: Mammals and Drosophila melanogaster share some striking similarities in spermatogenesis. Mitochondria in spermatids undergo dramatic morphological changes and syncytial spermatids are stripped from their cytoplasm and then individually wrapped by single membranes in an individualization process. In mammalian and fruit fly testis, components of the mitochondrial iron metabolism are expressed, but so far their function during spermatogenesis is unknown. Here we investigate the role of Drosophila mitoferrin (dmfrn), which is a mitochondrial carrier protein with an established role in the mitochondrial iron metabolism, during spermatogenesis. Results: We found that P-element insertions into the 5'-untranslated region of the dmfrn gene cause recessive male sterility, which was rescued by a fluorescently tagged transgenic dmfrn genomic construct (dmfrnvenus). Testes of mutant homozygous dmfrnSH115 flies were either small with unorganized content or contained some partially elongated spermatids, or testes were of normal size but lacked mature sperm. Testis squashes indicated that spermatid elongation was defective and electron micrographs showed mitochondrial defects in elongated spermatids and indicated failed individualization. Using a LacZ reporter and the dmfrnvenus transgene, we found that dmfrn expression in testes was highest in spermatids, coinciding with the stages that showed defects in the mutants. Dmfrn-venus protein accumulated in mitochondrial derivatives of spermatids, where it remained until most of it was stripped off during individualization and disposed of in waste bags. Male sterility in flies with the hypomorph alleles dmfrnBG00456 and dmfrnEY01302 over the deletion Df(3R)ED6277 was increased by dietary iron chelation and suppressed by iron supplementation of the food, while male sterility of dmfrnSH115/Df(3R)ED6277 flies was not affected by food iron levels. Conclusions: In this work, we show that mutations in the Drosophila mitoferrin gene result in male sterility caused by developmental defects. From the sensitivity of the hypomorph mutants to low food iron levels we conclude that mitochondrial iron is essential for spermatogenesis. This is the first time that a link between the mitochondrial iron metabolism and spermatogenesis has been shown. Furthermore, due to the similar expression patterns of some mitochondrial iron metabolism genes in Drosophila and mammals, it is likely that our results are applicable for mammals as well. [ABSTRACT FROM AUTHOR]

Background: In Drosophila, all the 64 clonally derived spermatocytes differentiate in syncytium inside two somatic-origin cyst cells. They elongate to form slender spermatids, which are individualized and then released into the seminal vesicle. During individualization, differentiating spermatids are organized in a tight bundle inside the cyst, which is expected to play an important role in sperm selection. However, actual significance of this process and its underlying mechanism are unclear. Results: We show that dynamic F-actin-based processes extend from the head cyst cell at the start of individualization, filling the interstitial space at the rostral ends of the maturing spermatid bundle. In addition to actin, these structures contained lamin, beta-catenin, dynamin, myosin VI and several other filopodial components. Further, pharmacological and genetic analyses showed that cytoskeletal stability and dynamin function are essential for their maintenance. Disruption of these F-actin based processes was associated with spermatid bundle disassembly and premature sperm release inside the testis. Conclusion: Altogether, our data suggests that the head cyst cell adheres to the maturing spermatid heads through F-actin-based extensions, thus maintaining them in a tight bundle. This is likely to regulate mature sperm release into the seminal vesicle. Overall, this process bears resemblance to mammalian spermiation. [ABSTRACT FROM AUTHOR]

Background: Clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein (Cas) systems are the latest addition to the plethora of gene-editing tools. These systems have been repurposed from their natural counterparts by means of both guide RNA and Cas nuclease engineering. These RNA-guided systems offer greater programmability and multiplexing capacity than previous generation gene editing tools based on zinc finger nucleases and transcription activator like effector nucleases. CRISPR-Cas systems show great promise for individualization of cancer precision medicine. Main body: The biology of Cas nucleases and dead Cas based systems relevant for in vivo gene therapy applications has been discussed. The CRISPR knockout, CRISPR activation and CRISPR interference based genetic screens which offer opportunity to assess functions of thousands of genes in massively parallel assays have been also highlighted. Single and combinatorial gene knockout screens lead to identification of drug targets and synthetic lethal genetic interactions across different cancer phenotypes. There are different viral and non-viral (nanoformulation based) modalities that can carry CRISPR-Cas components to different target organs in vivo. Conclusion: The latest developments in the field in terms of optimization of performance of the CRISPR-Cas elements should fuel greater application of the latter in the realm of precision medicine. Lastly, how the already available knowledge can help in furtherance of use of CRISPR based tools in personalized medicine has been discussed. [ABSTRACT FROM AUTHOR]

Background: Low back pain (LBP) is common among military veterans seeking treatment in Department of Veterans Affairs (VA) healthcare facilities. As chiropractic services within VA expand, well-designed pragmatic trials and implementation studies are needed to assess clinical effectiveness and program uptake. This study evaluated veteran stakeholder perceptions of the feasibility and acceptability of care delivery and research processes in a pilot trial of multimodal chiropractic care for chronic LBP. Methods: The qualitative study was completed within a mixed-method, single-arm, pragmatic, pilot clinical trial of chiropractic care for LBP conducted in VA chiropractic clinics. Study coordinators completed semi-structured, in person or telephone interviews with veterans near the end of the 10-week trial. Interviews were audiorecorded and transcribed verbatim. Qualitative content analysis using a directed approach explored salient themes related to trial implementation and delivery of chiropractic services. Results: Of 40 participants, 24 completed interviews (60% response; 67% male gender; mean age 51.7 years). Overall, participants considered the trial protocol and procedures feasible and reported that the chiropractic care and recruitment methods were acceptable. Findings were organized into 4 domains, 10 themes, and 21 subthemes. Chiropractic service delivery domain encompassed 3 themes/8 subthemes: scheduling process (limited clinic hours, scheduling future appointments, attendance barriers); treatment frequency (treatment sufficient for LBP complaint, more/less frequent treatments); and chiropractic clinic considerations (hire more chiropractors, including female chiropractors; chiropractic clinic environment; patient-centered treatment visits). Outcome measures domain comprised 3 themes/4 subthemes: questionnaire burden (low burden vs. time-consuming or repetitive); relevance (items relevant for LBP study); and timing and individualization of measures (questionnaire timing relative to symptoms, personalized approach to outcomes measures). The online data collection domain included 2 themes/4 subthemes: user concerns (little difficulty vs. form challenges, required computer skills); and technology issues (computer/internet access, junk mail). Clinical trial planning domain included 2 themes/5 subthemes: participant recruitment (altruistic service by veterans, awareness of chiropractic availability, financial compensation); and communication methods (preferences, potential barriers). Conclusions: This qualitative study highlighted veteran stakeholders' perceptions of VA-based chiropractic services and offered important suggestions for conducting a full-scale, veteran-focused, randomized trial of multimodal chiropractic care for chronic LBP in this clinical setting. Trial registration: ClinicalTrials.govNCT03254719 [ABSTRACT FROM AUTHOR]

Background: Current criteria for surfactant administration assume that hypoxia is a direct marker of lung-volume de-recruitment. We first introduced an early, non-invasive assessment of lung mechanics by the Forced Oscillation Technique (FOT) and evaluated its role in predicting the need for surfactant therapy.Objectives: To evaluate whether lung reactance (Xrs) assessment by FOT within 2 h of birth identifies infants who would need surfactant within 24 h; to eventually determine Xrs performance and a cut-off value for early detection of infants requiring surfactant.Methods: We conducted a prospective, observational, non-randomized study in our tertiary NICU in Milan. Eligible infants were born between 27+0 and 34+6 weeks' gestation, presenting respiratory distress after birth.Exclusion Criteria: endotracheal intubation at birth, major malformations participation in other interventional trials, parental consent denied. We assessed Xrs during nasal CPAP at 5 cmH2O at 10 Hz within 2 h of life, recording flow and pressure tracing through a Fabian Ventilator for off-line analysis. Clinicians were blinded to FOT results.Results: We enrolled 61 infants, with a median [IQR] gestational age of 31.9 [30.3; 32.9] weeks and birth weight 1490 [1230; 1816] g; 2 infants were excluded from the analysis for set-up malfunctioning. 14/59 infants received surfactant within 24 h. Xrs predicted surfactant need with a cut-off - 33.4 cmH2O*s/L and AUC-ROC = 0.86 (0.76-0.96), with sensitivity 0.85 and specificity 0.83. An Xrs cut-off value of - 23.3 cmH2O*s/L identified infants needing surfactant or respiratory support > 28 days with AUC-ROC = 0.89 (0.81-0.97), sensitivity 0.86 and specificity 0.77. Interestingly, 12 infants with Xrs < - 23.3 cmH2O*s/L (i.e. de-recruited lungs) did not receive surfactant and subsequently required prolonged respiratory support.Conclusion: Xrs assessed within 2 h of life predicts surfactant need and respiratory support duration in preterm infants. The possible role of Xrs in improving the individualization of respiratory management in preterm infants deserves further investigation. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease is a long-term, complex health condition. To improve or maintain quality of life, people with Parkinson's can have an active involvement in their care through self-management techniques. Given the complexity and individualization of self-management, people with Parkinson's will need support and encouragement from their healthcare professionals (HCPs). Despite the key role HCPs have in this, research has seldom explored their perspectives and understanding of self-management for people with Parkinson's.Methods: Multi-disciplinary teams providing care for people with Parkinson's across London, Coventry and Hertfordshire were approached and took part in either one of four focus groups or individual interviews. Forty-two HCPs, including a range of specialist doctors, general practitioners, allied health professionals, nurses, and social workers, took part in this study. Interviews were transcribed and analysed using thematic analysis to identify themes.Results: Four themes were developed from the data: 1) Empowerment of patients through holistic care and being person-centred; 2) Maximising motivation and capability for patients, for example using asset based approaches and increasing opportunities; 3) importance of empowerment of carers to support self-management and 4) contextual barriers to self-management such as the social context.Conclusions: This study is the first to explore the perspectives of HCPs on self-management in people with Parkinson's. Our findings have identified important considerations surrounding empowerment, motivation, carers and contextual barriers to better understand how we enable effective self-management techniques in people with Parkinson's. Research should build on these findings on to develop acceptable and effective self-management tools for use in practice with people affected by Parkinson's. [ABSTRACT FROM AUTHOR]

Background: MyDiabetesPlan is a web-based, interactive patient decision aid that facilitates patient-centred, diabetes-specific, goal-setting and shared decision-making (SDM) with interprofessional health care teams.Objective: Assess the feasibility of (1) conducting a cluster randomized controlled trial (RCT) and (2) integrating MyDiabetesPlan into interprofessional primary care clinics.Methods: We conducted a cluster RCT in 10 interprofessional primary care clinics with patients living with diabetes and at least two other comorbidities; half of the clinics were assigned to MyDiabetesPlan and half were assigned to usual care. To assess recruitment, retention, and resource use, we used RCT conduct logs and financial account summaries. To assess intervention fidelity, we used RCT conduct logs and website usage logs. To identify barriers and facilitators to integration of MyDiabetesPlan into clinical care across the IP team, we used audiotapes of clinical encounters in the intervention groups.Results: One thousand five hundred and ninety-seven potentially eligible patients were identified through searches of electronic medical records, of which 1113 patients met the eligibility criteria upon detailed chart review. A total of 425 patients were randomly selected; of these, 213 were able to participate and were allocated (intervention: n = 102; control: n = 111), for a recruitment rate of 50.1%. One hundred and fifty-one patients completed the study, for a retention rate of 70.9%. A total of 5745 personnel-hours and $6104 CAD were attributed to recruitment and retention activities. A total of 179 appointments occurred (out of 204 expected appointments-two per participant over the 12-month study period; 87.7%). Forty (36%), 25 (23%), and 32 (29%) patients completed MyDiabetesPlan at least twice, once, and zero times, respectively. Mean time for completion of MyDiabetesPlan by the clinician and the patient during initial appointments was 37 min. From the clinical encounter transcripts, we identified diverse strategies used by clinicians and patients to integrate MyDiabetesPlan into the appointment, characterized by rapport building and individualization. Barriers to use included clinician-related, patient-related, and technical factors.Conclusion: An interprofessional approach to SDM using a decision aid was feasible. Lower than expected numbers of diabetes-specific appointments and use of MyDiabetesPlan were observed. Addressing facilitators and barriers identified in this study will promote more seamless integration into clinical care. Trial registration Clinicaltrials.gov Identifier: NCT02379078. Date of Registration: February 11, 2015. Protocol version: Version 1; February 26, 2015. [ABSTRACT FROM AUTHOR]