Feasibility of targeted therapies in the adjuvant setting of early breast cancer in men: real-world data from a population-based registry.

BACKGROUND: Following the positive iDFS and OS results of the phase III clinical trials monarchE, NATALEE and OlympiA, new oral anticancer agents (the CDK4/6 inhibitors abemaciclib, ribociclib as well as the PARP inhibitor olaparib) have recently been introduced into the treatment of high-risk early breast cancer (eBC). However, only few male patients were included in these trials (0.4%, 0.6% and 0.3%, respectively). The objective of this real-world analysis was to determine the proportion of male patients with eBC fulfilling the clinical high-risk criteria of above-mentioned trials. PATIENTS AND METHODS: We conducted a data inquiry and analysis with the Cancer Registry of Baden-Württemberg of men with breast cancer diagnosed between January 1, 2015 and December 31, 2021. Men with eBC were identified and the number of patients at clinical high-risk according to the inclusion criteria of monarchE, NATALEE and OlympiA was assessed. RESULTS: Of 397 men with eBC, 354 (89.1%) had a HR + /Her2- and 4 (1.0%) a triple-negative subtype. 84 patients (21.2%) met the clinical high-risk criteria according to the monarchE, 189 (47.6%) those according to the NATALEE and 50 (12.6%) those according to the OlympiA trial. CONCLUSION: In a large real-world sample, more men with eBC are at clinical high risk according to the inclusion criteria of monarchE, NATALEE and OlympiA than would be expected in women. This is most likely due to more advanced stages at initial diagnosis in men. To evaluate whether CDK4/6 and PARP inhibitors improve prognosis also in men should be the topic of future real- world analyses.

Effectiveness of a Comprehensive School-Based Sex Education Program for Young Adolescents in the Netherlands.

Most sexual education programs traditionally focused on providing sexual information regarding the risks of sex. However, current studies on sexual behavior in youth show a need for truly comprehensive sex education approaches with a sex-positive focus on sexuality, that effectively improve sexual competence. Therefore, in the current study the effectiveness of "Love is…", a four lesson school-based program based on the Sexual Interactional Competence model and Attitude-Social-Influence-Self-Efficacy-model was studied. A cluster-randomized controlled trial on the effectiveness of "Love is…" was conducted in 2018-2020. The sample consisted of 1160 adolescents in grades 8 and 9 from nine schools in the Netherlands. The sample was 48% female, 34% Dutch/Caucasian, 41% none-religious and 50% higher educated. They were randomized at class level into a program group [n = 32 classes; 567 students (Mage = 13.74 (SD = 0.74))] and a control group [n = 31 classes; 593 students (Mage = 13.86 (SD = 0.73))]. Results showed that "Love is…" increased sexual knowledge, that adolescents in the program group showed less cyber victim blaming attitudes and increased in communications skills after the program. In conclusion, the current study shows that "Love is…" was effective not only on the knowledge level, but also regarding sexual attitudes and competences. However, due to the developmental process of sexuality, there is a necessity to continue lessons in following grades through booster sessions by reinforcing competences as communicating comfortably about sexuality.On 12 November 2019 the study design and hypotheses were registered in the Dutch Trial Registration, number NL8150. ( https://onderzoekmetmensen.nl/nl/trial/26676 ).

Spatiotemporal prediction of vancomycin-resistant Enterococcus colonisation.

BACKGROUND: Vancomycin-resistant enterococci (VRE) is the cause of severe patient health and monetary burdens. Antibiotic use is a confounding effect to predict VRE in patients, but the antibiotic use of patients who may have frequented the same ward as the patient in question is often neglected. This study investigates how patient movements between hospital wards and their antibiotic use can explain the colonisation of patients with VRE. METHODS: Intrahospital patient movements, antibiotic use and PCR screening data were used from a hospital in the Netherlands. The PageRank algorithm was used to calculate two daily centrality measures based on the spatiotemporal graph to summarise the flow of patients and antibiotics at the ward level. A decision tree model was used to determine a simple set of rules to estimate the daily probability of patient VRE colonisation for each hospital ward. The model performance was improved using a random forest model and compared using 30% test sample. RESULTS: Centrality covariates summarising the flow of patients and their antibiotic use between hospital wards can be used to predict the daily colonisation of VRE at the hospital ward level. The decision tree model produced a simple set of rules that can be used to determine the daily probability of patient VRE colonisation for each hospital ward. An acceptable area under the ROC curve (AUC) of 0.755 was achieved using the decision tree model and an excellent AUC of 0.883 by the random forest model on the test set. These results confirms that the random forest model performs better than a single decision tree for all levels of model sensitivity and specificity on data not used to estimate the models. CONCLUSION: This study showed how the movements of patients inside hospitals and their use of antibiotics could predict the colonisation of patients with VRE at the ward level. Two daily centrality measures were proposed to summarise the flow of patients and antibiotics at the ward level. An early warning system for VRE can be developed to test and further develop infection prevention plans and outbreak strategies using these results.

[Primary care psychology in Belgium: clinical characteristics and service use]. / Eerstelijns psychologische zorg in België: klinische kenmerken en zorggebruik.

BACKGROUND: Against the treatment gap and the long delays in seeking treatment for mental health problems, primary care psychology (PCP) was added to reimbursed outpatient mental health services in the Belgian healthcare system. AIM: To describe the characteristics of patients treated within the measure of reimbursement of PCP. METHOD: A total of 350 patients participated in an online survey at the start of their PCP treatment within one of the 31 mental healthcare networks in Belgium. Besides sociodemographic characteristics, they were questioned about their mental disorders, suicidality, service use, and delays in seeking treatment. RESULTS: Almost 90% of all patients screened positive for a lifetime and 12-month DSM-5 mental disorder, mostly anxiety and depressive disorders. Over 1/3 were experiencing suicidal thoughts and/or behaviors (STB) in the last 12 months. For 49.1% of patients, PCP was the first treatment ever. The median delay in seeking treatment was 6 years. CONCLUSION: PCP in Belgium serves mostly a clinical population with high proportions of lifetime and 12-month mental disorders and STB, and many of them have been in mental health treatment before. These findings raise the question whether PCP fits the needs for the patients that are treated.

A spatiotemporal simulation study on the transmission of harmful microorganisms through connected healthcare workers in a hospital ward setting.

BACKGROUND: Hand transmission of harmful microorganisms may lead to infections and poses a major threat to patients and healthcare workers in healthcare settings. The most effective countermeasure against these transmissions is the adherence to spatiotemporal hand hygiene policies, but adherence rates are relatively low and vary over space and time. The spatiotemporal effects on hand transmission and spread of these microorganisms for varying hand hygiene compliance levels are unknown. This study aims to (1) identify a healthcare worker occupancy group of potential super-spreaders and (2) quantify spatiotemporal effects on the hand transmission and spread of harmful microorganisms for varying levels of hand hygiene compliance caused by this group. METHODS: Spatiotemporal data were collected in a hospital ward of an academic hospital using radio frequency identification technology for 7 days. A potential super-spreader healthcare worker occupation group was identified using the frequency identification sensors' contact data. The effects of five probability distributions of hand hygiene compliance and three harmful microorganism transmission rates were simulated using a dynamic agent-based simulation model. The effects of initial simulation assumptions on the simulation results were quantified using five risk outcomes. RESULTS: Nurses, doctors and patients are together responsible for 81.13% of all contacts. Nurses made up 70.68% of all contacts, which is more than five times that of doctors (10.44%). This identifies nurses as the potential super-spreader healthcare worker occupation group. For initial simulation conditions of extreme lack of hand hygiene compliance (5%) and high transmission rates (5% per contact moment), a colonised nurse can transfer microbes to three of the 17 healthcare worker or patients encountered during the 98.4 min of visiting 23 rooms while colonised. The harmful microorganism transmission potential for nurses is higher during weeknights (5 pm - 7 am) and weekends as compared to weekdays (7 am - 5 pm). CONCLUSION: Spatiotemporal behaviour and social mixing patterns of healthcare can change the expected number of hand transmissions and spread of harmful microorganisms by super-spreaders in a closed healthcare setting. These insights can be used to evaluate spatiotemporal safety behaviours and develop infection prevention and control strategies.

Predicting quality of life during and post detention in incarcerated juveniles.

PURPOSE: Besides reducing recidivism, juvenile justice institutions aim to rehabilitate juvenile delinquents, in order for them to reintegrate in society. As such, improving quality of life (QoL), especially post detention, is an important treatment goal. However, research is primarily focused on recidivism as an outcome measure for juvenile detention. The aim of the current study is therefore to describe and predict QoL of detained young offenders up to 1 year after an initial assessment, and to examine whether QoL differs between youth who are still detained versus released. METHODS: A sample of 186 juveniles admitted to juvenile justice institutions in the Netherlands was assessed within the institution (initial assessment/T0), using psychosocial and neurobiological factors as predictors (self-control, treatment motivation, trauma, mental health problems, respiratory sinus arrhythmia). QoL (MANSA), as well as substance use (alcohol, cannabis) and daily activities (education, work) were assessed at first, second, and third follow-up (respectively 2.5 months, 4.5 months, and 12 months after T0). RESULTS: QoL increased from first to third follow-up, and was higher for individuals who were no longer detained. The model that best predicted higher QoL upon follow-up consisted of lower trauma and stronger parasympathetic nervous system reactivity. The effects of the predictors did not differ between the various follow-ups, nor between individuals who were or were not detained. CONCLUSION: Methods incorporating trauma-sensitive focus and relaxation techniques in treatment protocols in juvenile justice institutions may be of added value in improving the general functioning of these individuals.

Perioperative Outcomes of Myomectomy for Extreme Myoma Burden: Comparison of Surgical Approaches.

STUDY OBJECTIVE: To describe the perioperative outcomes of various modes of myomectomy (abdominal [AM], laparoscopic [LM], or robotic [RM]) in cases of extreme myoma burden. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: A tertiary academic center in Boston, Massachusetts. PATIENTS: All women who underwent an AM, LM, or RM for extreme myoma burden, defined as representing the upper quartile for specimen weight (≥434.6 g) or myoma count (≥7 myomas), between 2009 and 2016. INTERVENTIONS: Baseline demographics and perioperative outcomes were collected from review of medical records, including estimated blood loss, operative time, length of stay, and complications. Univariate linear and logistic regression analyses were conducted. MEASUREMENTS AND MAIN RESULTS: During the study period 659 women underwent myomectomy for extreme myoma burden; 47.2% of cases were AM, 28.1% LM, and 24.7% RM. Overall myoma burden differed across the 3 routes and was greatest in the AM group (mean weight: 696.2 ± 784.5 g for AM vs 586.6 ± 426.1 g for LM and 586.6 ± 426.1 g for RM; mean number: 16.8 ± 15.0 for AM vs 7.2 ± 7.0 for LM and 6.7 ± 4.7 for RM; p <.001 for both). The 3 routes differed in operative time and length of stay, with RM having the longest operative time (mean, 239.7 minutes; p <.001) and AM the longest length of stay (mean, 2.2 ± .9 days; p <.001). Other perioperative outcomes were similar across the surgical approaches. Increasing myoma burden was associated with an increased risk of perioperative complications for all surgical approaches, with a threshold of 13 myomas associated with an almost 2-fold higher risk of perioperative complications (odds ratio, 1.77; 95% confidence interval, 1.17-2.70; p = .009). Cumulative incidence of perioperative complications with increasing specimen weight was greater in the RM cases as compared with AM (p = .002) or LM (p = .020), whereas the cumulative incidence of perioperative complications with increasing myoma count was lowest with AM compared with LM (p <.001) or RM (p <.001). CONCLUSION: Myomectomy for extreme myomas is feasible using an abdominal, laparoscopic, or robotic approach. Increased myoma burden is associated with an increased risk of perioperative complications. A threshold of 13 myomas was associated with an almost 2-fold higher risk of perioperative complications for all modes. Perioperative complication outcomes were more favorable in AM or LM over RM with increased myoma weight and AM over LM or RM with increased myoma number.

Incident depression and mortality among people with different types of dementia: results from a longitudinal cohort study.

PURPOSE: The aim of this study was to investigate the independent and combined association of incident depression and dementia with mortality and to explore whether the magnitude of the association varies according to different types of dementia, including Alzheimer's disease and vascular dementia. METHODS AND DESIGN: The study was based on a population-based longitudinal cohort consisting of 9940 participants at baseline and followed for over 14 years. The sample used for the analyses included 6114 participants with available information on diagnosis of incident dementia and depression. For survival analyses, Cox regression models with incident dementia (n = 293; 5%) and incident depression (n = 746; 12%) as time-dependent variables were used. RESULTS: Cox models adjusted for relevant confounders indicated that comorbidity of incident vascular dementia and incident depression was associated with a much higher mortality risk (HR 6.99; 95% CI 3.84-12.75) than vascular dementia in the absence of depression (HR 2.80; 95% CI 1.92-4.08). In contrast, estimates for comorbidity of Alzheimer's disease and depression were slightly lower than those for Alzheimer in absence of depression (HR 3.56; 95% CI 1.83-6.92 and HR 4.19; 95% CI 2.97-5.90, respectively). Incident depression in the absence of incident dementia was only weakly associated with mortality. CONCLUSIONS: These findings indicate that depression and vascular dementia might have synergistic effects on mortality. The results have relevant public health implications for prevention, routine screening for and early treatment of depression among older people, especially those at risk of vascular dementia.

HBsAg loss after peginterferon-nucleotide combination treatment in chronic hepatitis B patients: 5 years of follow-up.

Combining peginterferon-alfa-2a (pegIFN) with a nucleotide analogue can result in higher rates of HBsAg loss than either therapy given alone. Here, we investigated the durability of the response to combination therapy in chronic hepatitis B (CHB) patients after 5 years of follow-up. In the initial study, 92 CHB patients (44 HBeAg-positive, 48 HBeAg-negative) with HBV DNA >100 000 c/mL (~20 000 IU/mL) and active hepatitis were treated for 48 weeks with pegIFN 180 µg/week and 10 mg adefovir dipivoxil daily. For the long-term follow-up (LTFU) study, patients were followed up for 5 years after the end of treatment. At year 5, 70 (32 HBeAg-positive, 38 HBeAg-negative) patients remained in the study. At year 5, 19% (6/32) of HBeAg-positive patients and 16% (6/38) of HBeAg-negative patients lost HBsAg, and no HBsAg seroreversion was observed. The 5-year cumulative Kaplan-Meier estimate for HBsAg loss was 17.2% for HBeAg-positive patients and 19.3% for HBeAg-negative patients. Fourteen of sixteen patients who lost HBsAg at any time point during follow-up developed anti-HBs antibodies (>10 IU/L). At year 5, in total 63% (20/32) of HBeAg-positive and 71% (27/38) of HBeAg-negative patients were retreated with nucleos(t)ide analogues during follow-up. The cumulative Kaplan-Meier estimate for retreatment was 60% of patients at year 5. At year 5 of follow-up, 18% of CHB patients treated with pegIFN/nucleotide analogue combination therapy had durable HBsAg loss and 88% of these had developed anti-HBs antibodies.

Hepatitis B Virus Pregenomic RNA Is Present in Virions in Plasma and Is Associated With a Response to Pegylated Interferon Alfa-2a and Nucleos(t)ide Analogues.

BACKGROUND: Treatment of patients with chronic hepatitis B (CHB) with nucleos(t)ide analogues (NAs) suppresses hepatitis B virus (HBV) DNA production but does not affect the synthesis of the RNA pregenome or HBV messenger RNA. Whether HBV RNA-containing particles continue to be secreted into the bloodstream remains controversial. METHODS: We developed a sensitive polymerase chain reaction (PCR) assay to quantify the HBV RNA load in a supernatant of NA-treated HepG2-2.2.15 cells and in plasma specimens from 20 patients with CHB who were receiving NA therapy and 86 patients treated with pegylated interferon alfa (Peg-IFN) and adefovir. RESULTS: Treatment of HepG2-2.2.15 cells with NAs for 9 days reduced HBV DNA levels (by 1.98 log10 copies/mL), whereas HBV RNA levels increased (by 0.47 log10 copies/mL; P < .05). During long-term NA treatment of patients with CHB, HBV RNA levels remained higher than HBV DNA levels. Peg-IFN-based treatment induced a stronger decrease in the HBV RNA load than NA monotherapy, and this decline was more pronounced in responders than in nonresponders. In HBV e antigen-negative patients, a lower baseline plasma HBV RNA level was independently associated with response to Peg-IFN and adefovir (odds ratio, 0.44; P = .019). Immunoprecipitation with HBV core antigen-specific antibodies after removal of the HBV surface antigen envelope demonstrated the association of plasma HBV RNA with virions. CONCLUSIONS: HBV RNA is present in virions in plasma specimens from patients with CHB. HBV RNA levels vary significantly from those of established viral markers during antiviral treatment, which highlights its potential as an independent marker in the evaluation of patients with CHB.

HLA-C and KIR combined genotype as new response marker for HBeAg-positive chronic hepatitis B patients treated with interferon-based combination therapy.

Current treatment for chronic hepatitis B infection (CHB) consists of interferon-based therapy. However, for unknown reasons, a large proportion of patients with CHB do not respond to this treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether HLA-C and KIR genotypes were associated with treatment outcome for CHB. Twelve SNPs in or near the HLA-C gene were genotyped in 86 CHB patients (41 HBeAg positive; 45 HBeAg negative) treated with peginterferon alfa-2a + adefovir. Genotyping of killer immunoglobin-like receptors (KIRs) was performed by SSP-PCR. One SNP in HLA-C (rs2308557) was significantly associated with combined response in HBeAg-positive CHB patients (P = 0.003). This SNP is linked to the HLA-C group C1 or C2 classification, which controls KIR binding. The combination of KIR2DL1 with its ligand HLA-C2 was observed significantly more often in HBeAg-positive patients with a combined response (13/14) than in nonresponders (11/27, P = 0.001). Patients with the KIR2DL1/C2 genotype had significantly higher baseline ALT levels (136 vs 50 U/L, P = 0.002) than patients without this combination. Furthermore, KIR2DL1-C2 predicted response independent of HBV genotype and ALT at baseline. HLA-C and KIR genotype is strongly associated with response in HBeAg-positive CHB patients treated with interferon-based therapy. In combination with other known response markers, HLA-C/KIR genotype could enable the selection of patients more likely to respond to interferon-based therapy.

Survival with nonmelanoma skin cancer in Germany.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common cancer in Germany, but detailed information on survival is lacking. OBJECTIVES: To provide survival estimates for female and male patients with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), sarcoma, adenocarcinoma and Merkel cell carcinoma. Further subgroup analyses were carried out by age, tumour stage and body site. METHODS: In total 459 640 patients diagnosed with NMSC in 1997-2011 were included from population-based cancer registers, covering a population of 33 million inhabitants. Age-standardized absolute and relative 5-year and 10-year survival were calculated using period analysis. RESULTS: The absolute and relative 5-year survival were 87·1% and 102·9% for BCC, 77·6% and 93·6% for SCC, 82·1% and 96·0% for sarcoma, 71·4% and 85·7% for adenocarcinoma and 60·0% and 70·7% for Merkel cell carcinoma, respectively. Higher age, female sex and advanced stage were associated with lower survival. CONCLUSIONS: A comprehensive overview of NMSC survival in Germany is provided. The differences between the NMSC subtypes require a more differentiated consideration of patient survival. The survival advantage of patients with BCC may be related to health-promoting factors related to the BCC diagnosis, such as changes to a healthier lifestyle.

Inhibited attachment behaviour and disinhibited social engagement behaviour as relevant concepts in referred home reared children.

BACKGROUND: Disorders of attachment and social engagement have mainly been studied in children, reared in institutions and foster care. There are few studies amongst home reared children living with biological parents. The aim of this study was to test the clinical significance of inhibited attachment behaviour and disinhibited social engagement behaviour in young home reared children, referred for treatment of emotional and behavioural problems, compared with young children in treatment foster care. METHODS: The Disturbances of Attachment Interview, Maltreatment Classification System, the Child Behaviour Checklist and Parenting Stress Index were used in 141 referred home reared children and 59 referred foster children, aged 2.0-7.9 years (M = 4.7, SE = 1.3), 71% boys. RESULTS: Inhibited attachment behaviour was less prevalent in the referred home reared group (9%) than in the foster care group (27%). Disinhibited social engagement behaviour was found in 42% of the home reared group, similar to the foster care group. Inhibited attachment behaviour and disinhibited social engagement behaviour were not associated with child maltreatment. More inhibited attachment behaviour was associated with clinical levels of child internalizing and externalizing behaviour in the home reared group, not in the foster care group. In both groups, more disinhibited social engagement behaviour was associated with clinical levels of externalizing behaviour and with more parenting stress. CONCLUSIONS: Even without evident links to maltreatment, results of this study suggest clinical significance of inhibited attachment behaviour and disinhibited social engagement behaviour in young home reared children referred for treatment of emotional and behavioural problems.

Genetic variants in DNA repair genes as potential predictive markers for oxaliplatin chemotherapy in colorectal cancer.

Oxaliplatin-based chemotherapy exerts its effects through generating DNA damage. Hence, genetic variants in DNA repair pathways could modulate treatment response. We used a prospective cohort of 623 colorectal cancer patients with stage II-IV disease treated with adjuvant/palliative chemotherapy to comprehensively investigate 1727 genetic variants in the DNA repair pathways as potential predictive markers for oxaliplatin treatment. Single nucleotide polymorphisms (SNP) associations with overall survival and recurrence-free survival were assessed using a Cox regression model. Pathway analysis was performed using the gamma method. Patients carrying variant alleles of rs3783819 (MNAT1) and rs1043953 (XPC) experienced a longer overall survival after treatment with oxaliplatin than patients who did not carry the variant allele, while the opposite association was found in patients who were not treated with oxaliplatin (false discovery rate-adjusted P-values for heterogeneity 0.0047 and 0.0237, respectively). The nucleotide excision repair (NER) pathway was found to be most likely associated with overall survival in patients who received oxaliplatin (P-value=0.002). Our data show that genetic variants in the NER pathway are potentially predictive of treatment response to oxaliplatin.

Smoking and survival of colorectal cancer patients: systematic review and meta-analysis.

Smoking is a risk factor for colorectal cancer (CRC) incidence and mortality. However, little is known on smoking and its association with survival after CRC diagnosis. We conducted a systematic review and meta-analysis to summarize current evidence. A systematic literature search was carried out in MEDLINE and ISI Web of Science. We included studies that analyzed recurrence-free survival, disease-free survival, all-cause, and CRC-specific mortality according to smoking status. Data were extracted in duplicate. Standard methods of meta-analysis were applied. Sixteen studies from 11 countries were identified, comprising a total sample size of 62 278 CRC patients. Overall, in the 16 included studies, current smoking and, to a lesser extent, former smoking were rather consistently associated with a poorer prognosis compared with never smokers. Meta-analyses yielded random-effects hazard ratio estimates (95% confidence intervals) for all-cause mortality of 1.26 (1.15-1.37) and 1.11 (0.93-1.33) for current and former smokers, compared with never smokers, respectively. In particular, 30-day mortality was found to be increased by between 49% and 100% among current compared with never smokers. Our results support the existence of detrimental effects of smoking on survival also after CRC diagnosis. Perspectives for enhancing prognosis of CRC patients by smoking abstinence deserve increased attention in further research and clinical practice.

Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant.

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.

High-energy versus low-energy extracorporeal shock wave therapy for calcifying tendinitis of the shoulder: which is superior? A meta-analysis.

BACKGROUND: There are several treatment options for calcifying tendinitis of the shoulder. The next step treatment after conservative treatment fails is still a matter of dispute. Extracorporeal shock wave therapy (ESWT) has been shown to be a good alternative to surgery, but the best treatment intensity remains unknown. High-energy ESWT is much more painful, more expensive, and usually is done in an inpatient setting, whereas low-energy ESWT can be performed in an outpatient setting by a physical therapist. QUESTIONS/PURPOSES: A systematic review and meta-analysis of randomized trials was performed to answer two clear research questions: (1) Is there a greater increase in the Constant-Murley score in patients treated with high-energy ESWT compared with those treated with low-energy ESWT by 3 months and by 6 months? (2) Is there a greater chance of complete resorption of the calcifications in patients treated with high-energy ESWT compared with those treated with low-energy ESWT by 3 months and by 6 months? METHODS: Five relevant electronic online databases, Medline (through PubMed), EMBASE (through OVID), Cinahl (through EBSCO), Web of Science, and the Cochrane Central Register of Controlled Trials, were systematically searched. We also crosschecked the reference lists of articles and reviews for possible relevant studies. Eligible for inclusion were all randomized controlled trials (RCTs) that compared high-energy ESWT (> 0.28 mJ/mm(2)) with low-energy ESWT (< 0.08 mJ/mm(2)). One author examined titles and abstracts of each identified study to assess study eligibility. Two reviewers independently extracted data and assessed the risk of bias and study quality. The primary outcome measure, the Constant-Murley score, was assessed by comparing mean functional outcome scores between the groups. Secondary outcomes were assessed using odds ratios, when appropriate data were pooled. Based on this process, five RCTs (359 participants) were included. RESULTS: All five RCTs showed greater improvement in functional outcome (Constant-Murley score) in patients treated with high-energy ESWT compared with patients treated with low-energy ESWT at 3 and 6 months. The 3-month mean difference was 9.88 (95% CI, 9.04-10.72, p < 0.001; 6-month data could not be pooled). Furthermore, high-energy ESWT more often resulted in complete resorption of the deposits at 3 months. The corresponding odds ratio was 3.40 (95% CI, 1.35-8.58) and p = 0.009 (6-month data could not be pooled). CONCLUSION: When shock wave therapy is chosen, high-energy shock wave therapy is more likely to result in improved Constant-Murley score and resorption of the deposits compared with low-energy therapy. LEVEL OF EVIDENCE: Level I, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Low-Fidelity Prototype of a Sensor-Dependent Interaction Platform: Formative Evaluation With Informal Caregivers of Older Adults With Cognitive Impairment.

BACKGROUND: Unobtrusive sensing technologies developed for monitoring deviant behaviors in older adult care require integration with an interaction platform to facilitate the flow of information between older adults and their caregivers. However, the continuous monitoring capabilities generate a considerable amount of data that must be interpreted, filtered, and personalized before being communicated to the informal caregivers based on their specific care needs and requirements. OBJECTIVE: For the effective implementation of unobtrusive sensing solutions (USSs) in the care of older adults with cognitive impairment, we aimed to explore the expectations and preconditions regarding the implementation of USSs from the perspective of informal caregivers. Subsequently, we designed and evaluated a low-fidelity prototype of an interaction platform for its conceptual workflow and usability, incorporating persuasive system design features based on the needs and requirements of informal caregivers. METHODS: Overall, 6 informal caregivers of older adults with cognitive impairment living alone participated in this qualitative interview study. We explored the expectation and preconditions regarding implementation through open-ended questions and conducted a formative evaluation (usability study with a think-aloud approach) to evaluate the conceptual workflow and used persuasive system design features in the interaction platform. Overall, a combination of inductive and thematic analyses was used to analyze the interviews. RESULTS: The results of this study present both positive and negative outcome expectations regarding the implementation of USSs, highlighting benefits such as objective decision-making and peace of mind and concerns about information overload and the potential substitution of human contact. Strategic information communication agreements between informal and formal caregivers were deemed crucial for the successful implementation of USSs in care. Overall, informal caregivers had a positive experience with the low-fidelity prototype of the interaction platform, particularly valuing the personalization feature. CONCLUSIONS: In conclusion, to achieve successful implementation, a holistic design approach is necessary, and equal consideration should be given to the personalization-privacy paradox to balance users' needs and privacy.

Study populations for period analyses of cancer survival.

BACKGROUND: Period analysis is increasingly used to compute long-term cancer survival, as it provides better prediction of survival of newly diagnosed patients than traditional cohort analysis. However, the patient population to which period survival estimates best pertain to and which should be described in a study is less obvious. METHODS: Using Finnish Cancer Registry data on 23 common cancer sites, age-standardized period estimates of 5-, 10-, 15-, and 20-year relative survival were computed for each 2-, 5-, and 10-year calendar period in 1954-2003 and compared with survival estimates for two cohorts by means of mean, mean absolute and mean squared differences: a full cohort of all patients potentially contributing some data to the survival analysis and a restricted cohort of patients diagnosed in the period of interest. RESULTS: In most computations, survival estimates for the full cohorts were on average closer to the period estimates for the majority of cancer sites. For 10-year survival, results were less obvious with respect to the mean difference. However, mean squared and mean absolute differences were smaller for the majority of cancers when using the full cohort. CONCLUSION: Our results suggest that the full cohort should be described in reports of period survival analysis.

Which screening strategy should be offered to women with BRCA1 or BRCA2 mutations? A simulation of comparative cost-effectiveness.

BACKGROUND: There is no consensus on the most effective strategy (mammography or magnetic resonance imaging (MRI)) for screening women with BRCA1 or BRCA2 mutations. The effectiveness and cost-effectiveness of the Dutch, UK and US screening strategies, which involve mammography and MRI at different ages and intervals were evaluated in high-risk women with BRCA1 or BRCA2 mutations. METHODS: Into a validated simulation screening model, outcomes and cost parameters were integrated from published and cancer registry data. Main outcomes were life-years gained and incremental cost-effectiveness ratios. The simulation was situated in the Netherlands as well as in the United Kingdom, comparing the Dutch, UK and US strategies with the population screening as a reference. A discount rate of 3% was applied to both costs and health benefits. RESULTS: In terms of life-years gained, the strategies from least to most cost-effective were the UK, Dutch and US screening strategy, respectively. However, the differences were small. Applying the US strategy in the Netherlands, the costs were €43 800 and 68 800 for an additional life-year gained for BRCA1 and BRCA2, respectively. At a threshold of €20 000 per life-year gained, implementing the US strategy in the Netherlands has a very low probability of being cost-effective. Stepping back to the less-effective UK strategy would save relatively little in costs and results in life-years lost. When implementing the screening strategies in the United Kingdom, the Dutch, as well as the US screening strategy have a high probability of being cost-effective. CONCLUSION: From a cost-effectiveness perspective, the Dutch screening strategy is preferred for screening high-risk women in the Netherlands as well as in the United Kingdom.