Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of age at diagnosis on prostate cancer treatment and survival.

PURPOSE Older men are more likely to be diagnosed with high-risk prostate cancer and to have lower overall survival. As a result, age often plays a role in treatment choice. However, the relationships among age, disease risk, and prostate cancer-specific survival have not been well established. PATIENTS AND METHODS We studied men in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database with complete risk, treatment, and follow-up information. High-risk patients were identified by using the validated Cancer of the Prostate Risk Assessment (CAPRA) score. Competing risks regression was used to identify the independent impact of age on cancer-specific survival. We also analyzed the effect of local treatment on survival among older men with high-risk disease. RESULTS In all, 26% of men age ≥ 75 years presented with high-risk disease (CAPRA score 6 to 10). Treatment varied markedly with age across risk strata; older men were more likely to receive androgen deprivation monotherapy. Controlling for treatment modality alone, or for treatment and risk, age did not independently predict cancer-specific survival. Furthermore, controlling for age, comorbidity, and risk, older men with high-risk tumors receiving local therapy had a 46% reduction in mortality compared with those treated conservatively. CONCLUSION Older patients are more likely to have high-risk prostate cancer at diagnosis and less likely to receive local therapy. Indeed, underuse of potentially curative local therapy among older men with high-risk disease may in part explain observed differences in cancer-specific survival across age strata. These findings support making decisions regarding treatment on the basis of disease risk and life expectancy rather than on chronologic age.
Repeat genital Chlamydia trachomatis testing rates in young adults in England, 2010

Objectives To explore patterns of repeat chlamydia testing among young people in England and factors associated with testing positive at repeat test. Methods We analysed chlamydia testing among 15 to 24-year-olds in England in a single calendar year (2010) using data from the genitourinary medicine clinic activity dataset (GUMCAD) and tests reported through the National Chlamydia Screening Programme (NCSP). Case records were linked using patient clinic numbers (GUMCAD), or by matching date of birth, gender and postcode (NCSP). Individuals could not be linked between datasets. The incidence of repeat testing was estimated using survival analysis. Risk factors for testing positive at repeat test were explored using multivariable logistic regression. Results 1 235 058 tests in the NCSP dataset and 502 095 in GUMCAD were included. The incidence of repeat testing was 18.4 and 26.1 per 100 person years in the NCSP dataset and GUMCAD respectively. Among NCSP repeat tests, the proportion testing positive was higher in those reporting recent change of sexual partner (adjusted OR males 1.44; females 1.52), and among those with a positive compared to a negative baseline test (adjusted OR males 2.57; females 1.95). Conclusions We observed moderate levels of repeat testing within a year. Considering the frequency of partner change among young people, more could be done to encourage re-testing upon change of sexual partner. Increasing re-testing following a positive test could probably identify unresolved or repeat infections that may otherwise go untreated. Work to establish the optimum approach to repeat testing in England is now warranted.
Changes in cardiac biomarkers during doxorubicin treatment of pediatric patients with high-risk acute lymphoblastic leukemia: associations with long-term echocardiographic outcomes.

PURPOSE Doxorubicin causes cardiac injury and cardiomyopathy in children with acute lymphoblastic leukemia (ALL). Measuring biomarkers during therapy might help individualize treatment by immediately identifying cardiac injury and cardiomyopathy. PATIENTS AND METHODS Children with high-risk ALL were randomly assigned to receive doxorubicin alone (n = 100; 75 analyzed) or doxorubicin with dexrazoxane (n = 105; 81 analyzed). Echocardiograms and serial serum measurements of cardiac troponin T (cTnT; cardiac injury biomarker), N-terminal pro-brain natriuretic peptide (NT-proBNP; cardiomyopathy biomarker), and high-sensitivity C-reactive protein (hsCRP; inflammatory biomarker) were obtained before, during, and after treatment. RESULTS cTnT levels were increased in 12% of children in the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group before treatment but in 47% and 13%, respectively, after treatment (P = .005). NT-proBNP levels were increased in 89% of children in the doxorubicin group and in 92% of children in the doxorubicin-dexrazoxane group before treatment but in only 48% and 20%, respectively, after treatment (P = .07). The percentage of children with increased hsCRP levels did not differ between groups at any time. In the first 90 days of treatment, detectable increases in cTnT were associated with abnormally reduced left ventricular (LV) mass and LV end-diastolic posterior wall thickness 4 years later (P < .01); increases in NT-proBNP were related to an abnormal LV thickness-to-dimension ratio, suggesting LV remodeling, 4 years later (P = .01). Increases in hsCRP were not associated with any echocardiographic variables. CONCLUSION cTnT and NT-proBNP may hold promise as biomarkers of cardiotoxicity in children with high-risk ALL. Definitive validation studies are required to fully establish their range of clinical utility.
The Pilates® Method in the treatment of lower back pain

Introduction The Pilates® method incorporates a number of the guidelines recommended for therapeutic exercises considered to be effective in the treatment of chronic lower back pain, such as the contraction of the transversus abdominis and multifidus muscles, associated with breathing, while taking into account the individual characteristics of patients. Objective To assess the effects of the Pilates® method on the treatment of lower back pain. Method This systematic review includes papers published from 2000 to 2010 in the BIREME, LILACS, MEDLINE and SciELO databases. The keywords used were spinal stabilization, Pilates®, and back pain and their equivalents in Portuguese. Results Imbalance among the trunk’s agonist-antagonist muscles and the ineffective activation of the transversus abdominis are risk factors for the onset of lower back pain that can be mitigated with the practice of Pilates®-based exercises. Conclusion The method has clinical effects similar to those obtained with traditional stabilization exercises and Back School exercises in the treatment of chronic lower back pain and are considered more satisfactory than conservative treatments.
Randomized, double-blind, placebo-controlled, phase II trial of sorafenib and erlotinib or erlotinib alone in previously treated advanced non-small-cell lung cancer.

PURPOSE Sorafenib, an oral multikinase inhibitor, has shown preliminary activity in non-small-cell lung cancer (NSCLC). Patients with advanced NSCLC were treated with erlotinib with or without sorafenib in this multicenter phase II trial. PATIENTS AND METHODS Key eligibility criteria included the following: stage IIIB or IV NSCLC; one to two prior regimens; Eastern Cooperative Oncology Group performance status of 0 to 2; and measurable disease. Patients were randomly assigned 2:1 to sorafenib (400 mg orally twice a day) plus erlotinib (150 mg orally daily) or placebo plus erlotinib and stratified by squamous/nonsquamous histology and prior bevacizumab. Treatment efficacy, measured by progression-free survival (PFS) and overall response rate (ORR), was compared. Treatment of 168 patients allowed detection of 40% improvement in the historical PFS of 2.2 months with single-agent erlotinib. RESULTS One hundred sixty-eight patients enrolled from February 2008 to February 2009. Clinical characteristics of the two groups were similar. ORRs for sorafenib/erlotinib and placebo/erlotinib were 8% and 11%, respectively (P = .56); disease control rates were 54% and 38%, respectively (P = .056). Median PFS was 3.38 months for sorafenib/erlotinib versus 1.94 months for placebo/erlotinib (hazard ratio, 0.86; 95% CI, 0.60 to 1.22; P = .196). Seventy-two patients consented to analyses of tumor epidermal growth factor receptor (EGFR). In 67 patients with EGFR wild-type (WT) tumors, median PFS was 3.38 months for sorafenib/erlotinib versus 1.77 months for placebo/erlotinib (P = .018); median overall survival (OS) was 8 months for sorafenib/erlotinib versus 4.5 months for placebo/erlotinib (P = .019). An OS advantage for sorafenib/erlotinib was suggested among 43 patients with fluorescent in situ hybridization (FISH) EGFR-negative tumors (P = .064). Both regimens were tolerable, with modest toxicity increase with sorafenib. CONCLUSION Although there was little difference in ORR or PFS, subset analyses in EGFR WT and EGFR FISH-negative patients suggest a benefit for the combination of erlotinib/sorafenib compared with single-agent erlotinib with respect to PFS and OS.
Physical activity among older people living alone in Shanghai, China

Objective: To investigate physical activity among older people living alone in Shanghai, People’s Republic of China, and key factors contributing to their physical activity. Methods: A cross-sectional questionnaire survey was administered in nine communities in Shanghai, using a stratified random cluster sample: 521 community-dwelling older people living alone (aged 60 years and above) completed a structured questionnaire through face-to-face interviews. Their physical activity was measured using their self-reported frequency of engaging in different types of activities. Other data collected included self-rated health, number of chronic diseases, depression, functional ability, loneliness, social support and socio-demographic variables. Results: Only 16.7% of participants reported adequate physical activity, defined as performing at least 30 minutes of moderate/strenuous exercise on at least 5 days per week. A younger age, a lower level of education, better functional ability and walking outside the home 5 – 7 days per week increased the likelihood of adequate physical activity. Gender, self-rated health, number of chronic diseases, depression and social support also had relationships with physical activity levels. Conclusion: The prevalence of adequate physical activity in older people living alone in Shanghai was low. In this population, appropriate health education interventions to promote physical activity levels are needed.
Monitoring antimicrobial resistance in Neisseria gonorrhoeae in selected countries of the WHO South-East Asia Region between 2009 and 2012: a retrospective analysis

Objective The aim of the present study was to retrospectively analyse the data reported on antimicrobial resistance (AMR) in Neisseria gonorrhoeae in six South-East Asia Region countries from 2009 to 2012 following the revitalisation of the WHO global Gonococcal Antimicrobial Surveillance Program (GASP). Methods AMR data were generated for 7 antibiotics of 4675 isolates in 18 focal point laboratories using the calibrated dichotomous sensitivity (CDS) or Clinical and Laboratory Standards Institute (CLSI) methods and minimal inhibitory concentration testing by Etest in some of the centres. The results were interpreted using the breakpoints recommended. Results High-level resistance to traditional antibiotics, penicillin (25% to 100%) and tetracycline (10% to 100%) and the previously recommended ciprofloxacin (38% to 100%) was observed in all the countries. Overall, >90% of less susceptible and resistant isolates to penicillin and ciprofloxacin were identified from 15 laboratories. Decreased susceptibility to ceftriaxone and cefpodoxime was reported by nine and eight centres, respectively. Resistance to spectinomycin (0.6% to 10.5%) and azithromycin (<5%) was reported only by three centres. The increasing trends of resistance towards penicillin, tetracycline and ciprofloxacin were demonstrated in Bhutan, India, Sri Lanka and Thailand, and no large intercountry variations were evident. Insignificant trends in decreased susceptibility towards ceftriaxone were reported. Conclusions Expansion of the WHO GASP facilitated enhanced AMR surveillance to meet the ongoing challenges of control of gonococcal AMR. The results highlight that the emergence of decreased susceptibility to ceftriaxone and resistance to spectinomycin and azithromycin will unavoidably lead to loss of therapeutic options, and a search for new effective agents needs to be initiated to respond to the emergence of resistant isolates.
Maximising the effectiveness of the National Chlamydia Screening Programme in England: should we routinely retest positives?

Realising the individual and potential population benefits of any chlamydia screening programme depends on good case management. At the very least, this should include the provision of effective and timely antibiotic treatment, finding and treating infected sexual partner(s), and the provision of condoms and safer sex advice.1–3 The papers in this issue and several previously published studies lead us to question whether retesting of people who test positive should also be a routine part of clinical practice. Several countries already recommend retesting 3–12 months after a chlamydia diagnosis.4–7 In England, the National Chlamydia Screening Programme (NCSP) recommends that sexually active young adults be tested annually and on change of sexual partner, but there is no recommendation to routinely retest positives more frequently.3 Should there be? The clinical arguments for retesting are strong. First, we know from prospective8–11 and passive12 ,13 follow-up studies that individuals who test positive for chlamydia are at considerably higher risk of subsequent chlamydia infection than those who test negative. Retesting could therefore lead to considerably greater numbers of infections being diagnosed and treated. In a …
Genotype-guided tamoxifen dosing increases active metabolite exposure in women with reduced CYP2D6 metabolism: a multicenter study.

PURPOSE We examined the feasibility of using CYP2D6 genotyping to determine optimal tamoxifen dose and investigated whether the key active tamoxifen metabolite, endoxifen, could be increased by genotype-guided tamoxifen dosing in patients with intermediate CYP2D6 metabolism. PATIENTS AND METHODS One hundred nineteen patients on tamoxifen 20 mg daily ≥ 4 months and not on any strong CYP2D6 inhibiting medications were assayed for CYP2D6 genotype and plasma tamoxifen metabolite concentrations. Patients found to be CYP2D6 extensive metabolizers (EM) remained on 20 mg and those found to be intermediate (IM) or poor (PM) metabolizers were increased to 40 mg daily. Eighty-nine evaluable patients had tamoxifen metabolite measurements repeated 4 months later. RESULTS As expected, the median baseline endoxifen concentration was higher in EM (34.3 ng/mL) compared with either IM (18.5 ng/mL; P = .0045) or PM (4.2 ng/mL; P < .001). When the dose was increased from 20 mg to 40 mg in IM and PM patients, the endoxifen concentration rose significantly; in IM there was a median intrapatient change from baseline of +7.6 ng/mL (-0.6 to 23.9; P < .001), and in PM there was a change of +6.1 ng/mL (2.6 to 12.5; P = .020). After the dose increase, there was no longer a significant difference in endoxifen concentrations between EM and IM patients (P = .84); however, the PM endoxifen concentration was still significantly lower. CONCLUSION This study demonstrates the feasibility of genotype-driven tamoxifen dosing and demonstrates that doubling the tamoxifen dose can increase endoxifen concentrations in IM and PM patients.
WT1 mutation and 11P15 loss of heterozygosity predict relapse in very low-risk wilms tumors treated with surgery alone: a children's oncology group study.

PURPOSE Children's Oncology Group defines very low-risk Wilms tumors (VLRWT) as stage I favorable histology Wilms tumors weighing less than 550 g in children younger than 24 months of age. VLRWTs may be treated with nephrectomy alone. However, 10% to 15% of VLRWTs relapse without chemotherapy. Previous studies suggest that VLRWTs with low WT1 expression and/or 11p15 loss of heterozygosity (LOH) may have increased risk of relapse. The current study validates these findings within prospectively identified children with VLRWT who did not receive adjuvant chemotherapy. PATIENTS AND METHODS Fifty-six VLRWTs (10 relapses) were analyzed for mutation of WT1, CTNNB1, and WTX; for 11p15 LOH using microsatellite analysis; and for H19DMR and KvDMR1 methylation. RESULTS 11p15 LOH was identified in 19 (41%) of 46 evaluable VLRWTs and was significantly associated with relapse (P < .001); 16 of 19 were isodisomic for 11p15. WT1 mutation was identified in nine (20%) of 45 evaluable VLRWTs and was significantly associated with relapse (P = .004); all nine cases also had 11p15 LOH. All evaluable tumors showing LOH by microsatellite analysis also showed LOH by methylation analysis. Retention of the normal imprinting pattern was identified in 24 of 42 evaluable tumors, and none relapsed. Loss of imprinting at 11p15 was identified in one of 42 tumors. CONCLUSION WT1 mutation and 11p15 LOH are associated with relapse in patients with VLRWTs who do not receive chemotherapy. These may provide meaningful biomarkers to stratify patients for reduced chemotherapy in the future. VLRWTs show a different incidence of WT1 mutation and 11p15 imprinting patterns than has been reported in Wilms tumors of all ages.
Initial evaluation of use of an online partner notification tool for STI, called ‘suggest a test’: a cross sectional pilot study

Objectives Partner notification is crucial for sexually transmitted infection (STI) control. We developed Suggestatest.nl (SAT), an internet-based notification system for verified diagnoses of STI/HIV. Methods SAT uses email, short message service, postal letter or a gay dating site to notify sexual contacts. SAT was piloted at the Public Health STI clinics in two major cities in the Netherlands. We evaluated SAT from March to July 2012 by analysing SAT notifications linked with epidemiological data. Determinants for SAT use were assessed using multivariable logistic regression analysis. Results Of 988 index clients receiving a SAT code, overall 139 (14%) notified through SAT, sending 505 notifications (median 2), 84% by text messaging and 15% by email; 88% non-anonymously. Of those intending to use SAT, 23% notified with SAT. Intention to use SAT was the only independent determinant of SAT use in heterosexuals and men who have sex with men. Among the 67 SAT users in Rotterdam, 56% (225/402) of their partners at risk were contactable, and 95% (213/225) of those were notified using SAT. 58% of SAT-notified partners accessed the SAT-website and 20% of them subsequently consulted the STI clinics. STI positivity in partners was lower in those notified by SAT (28% (32/116)) than in those with contact cards (45% (68/152); p<0.001). Conclusions Although the challenges posed by non-contactable partners are not solved by SAT, it is a valuable novel tool for notification of verified STI diagnoses by index patients and providers. In addition to current standard partner notification practice it suits a small number of clients, especially those reporting more than one partner.
Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy.

PURPOSE Trastuzumab resistance has been linked to activation of the phosphoinositol 3-kinase (PI3K) pathway. Phosphatase and tensin homolog (PTEN) is a dual phosphatase that counteracts the PI3K function; PTEN loss leads to activation of the Akt cascade and the downstream mammalian target of rapamycin (mTOR). Preclinical studies demonstrated that mTOR inhibition sensitized the response to trastuzumab in mice with HER2 overexpressing and PTEN-deficient breast xenografts. Our trial evaluated the safety and efficacy of the combination of everolimus and trastuzumab in women with HER2-overexpressing metastatic breast cancer (MBC) that progressed on trastuzumab-based therapy. PATIENTS AND METHODS This represents a pooled analysis (n = 47), stemming from two trials that occurred concurrently in The University of Texas MD Anderson Cancer Center, Beth Israel Deaconess Medical Center, and Dana-Farber Cancer Institute. Patients with HER2-overexpressing MBC who had progressed on trastuzumab-based therapy received trastuzumab every 3 weeks in combination with daily everolimus. RESULTS Among 47 patients, the combination of everolimus and trastuzumab provided partial responses in seven patients (15%) and persistent stable disease (lasting 6 months or longer) in nine patients (19%), resulting in a clinical benefit rate of 34%. The median progression-free survival (PFS) was 4.1 month. Fatigue, infection, and mucositis were the predominant nonhematologic toxicities. Trastuzumab did not have significant influence on the pharmacokinetic profile of everolimus. Patients with PTEN loss demonstrated decreased overall survival (P = .048). However, PFS was not affected by PTEN loss. CONCLUSION Inhibition of mTOR results in clinical benefit and disease response in patients with trastuzumab-resistant HER2-overexpressing MBC.
The Clinical Course of Patients with Atrial Fibrillation and Flutter Admitted to Medical Intensive Care Units

To better understand the clinical course of patients with atrial fibrillation and flutter who are admitted to medi cal intensive care units (ICUs), we retrospectively re viewed the course of patients with either of these rhythms present on admission. Patients with atrial fibril lation and flutter accounted for 10% of the admissions to a combined intensive and coronary care unit over a 5- year period. These patients had an ICU mortality rate of 9.4%; the ICU deaths occurred exclusively in a subgroup of patients (60%) whose arrhythmia was associated with other serious illnesses. The subgroup of patients presenting with atrial fibrillation and flutter only had a benign course; this subgroup included patients in whom alcohol intake contributed to the rhythm disturbance. Complications occurred in 40% of patients and were predicted with multivariate analysis by (1) the presence of alveolar edema on the initial chest roentgenogram; (2) female sex; (3) diastolic blood pressure less than or equal to 95; (4) chest pain lasting more than 2 hours; and (5) ischemia on the presenting electrocardiogram. Prospective application of these criteria may be helpful in deciding which patients could be initially triaged to non-ICU areas, thereby resulting in more efficient ICU use.