Miracle-dz/UniFAR-FTUs huggingface dataset:
Castration-resistant prostate cancer: descriptive yet pejorative?

TO THE EDITOR: The euphemistic term castration-resistant prostate cancer (CRPC) has slowly entered the everyday lexicon of those who study and treat prostate cancer. Ahmann and Crawford utilized this term in 1987. Emanating from what used to be called hormonerefractory prostate cancer and/or androgen-independent prostate cancer, this CRPC consensus definition was first formally reintroduced at a 2005 ODAC discussion on prostate cancer trial end points. Subsequently, in 2008, it was specifically defined in a Prostate Cancer Working Group Guidelines report, published in Journal of Clinical Oncology. At that time, Scher et al recognized that despite medical or surgical castration, prostate cancers were still sensitive to subcastrate levels of androgens, either emanating from the adrenal cortex or from prostate cancer cells themselves (with direct intracrine activation of the androgen receptor cascade). However, there have been some concerns expressed by clinicians, and more importantly by patients themselves, that the term castration implies some sort of testicular removal, which has a negative connotation for many men who have this disease. Hormone-refractory prostate cancer and androgen-independent prostate cancer did not have this perceived stigma, but in contrast, they have proven to be considerably inaccurate, as secondgeneration androgen deprivation therapy clinical trials are beginning to demonstrate. Therefore, we would like to propose that a term such as endocrineresistant prostate cancer may be a better description to utilize with our colleagues and patients. It is both accurate and less emotionally charged. Seen in this fashion, it gives us in the field, as well as our patients, a clearer way to view therapeutic options (which will increase significantly in the years to come). Therapeutically, if patients knew their disease was either endocrine sensitive or endocrine resistant, potentially approvable agents like Abiraterone, MDV-3100, and even estrogenic compounds could be clearly delineated from the evolving nonhormonal options that are also coming down the pike, like immunotherapy, targeted agents, and newer chemotherapies.
Admitting medication errors: five critical concepts

De Winter et al ( see page 371 ) studied 3594 patients admitted to hospital through an emergency department and found that 59% of patients had a discrepancy between the physician's medication history and a pharmacist technician's structured medication history.1 This result is consistent with over 20 small studies (median sample size 104 patients) showing 61–67% of patients have at least one discrepancy in the medication history at the time of hospital admission.2 There are at least three good reasons to obtain an accurate medication history at the time of hospital admission. First, more than 1 in 9 emergency department visits are due to drug-related adverse events.3 An accurate medication history will be the cornerstone for diagnosing this common problem. Second, medication history errors may result in incorrect medication orders and incorrect treatment during the admission, leading to patient harm. Third, an accurate medication history is the foundation for accurate medication instructions and prescriptions at the time of hospital discharge. Medication reconciliation (Med Rec) at admission is the process of obtaining the best-possible medication history (BPMH), and using this list to provide correct medications to patients at the time of hospital admission. Med Rec at admission is the cornerstone of Med Rec during subsequent transfers and at discharge. Med Rec is a major patient safety priority for safety improvement organisations such as the WHO,4 and hospital accreditors.5 Well-designed medication reconciliation programmes can reduce medication discrepancies6 and potential adverse drug events,7 although there are no studies to show a reduction in preventable adverse drug events. Successful medication reconciliation implementation is a challenge, as evidenced by the Joint Commission's recent decision …
Prevalence of rheumatic and musculoskeletal diseases and their impact on health-related quality of life, physical function and mental health in Portugal: results from EpiReumaPt– a national health survey

Objectives To estimate the national prevalence of rheumatic and musculoskeletal diseases (RMDs) in the adult Portuguese population and to determine their impact on health-related quality of life (HRQoL), physical function, anxiety and depression. Methods EpiReumaPt is a national health survey with a three-stage approach. First, 10 661 adult participants were randomly selected. Trained interviewers undertook structured face-to-face questionnaires that included screening for RMDs and assessments of health-related quality of life, physical function, anxiety and depression. Second, positive screenings for ≥1 RMD plus 20% negative screenings were invited to be evaluated by a rheumatologist. Finally, three rheumatologists revised all the information and confirmed the diagnoses according to validated criteria. Estimates were computed as weighted proportions, taking the sampling design into account. Results The disease-specific prevalence rates (and 95% CIs) of RMDs in the adult Portuguese population were: low back pain, 26.4% (23.3% to 29.5%); periarticular disease, 15.8% (13.5% to 18.0%); knee osteoarthritis (OA), 12.4% (11.0% to 13.8%); osteoporosis, 10.2% (9.0% to 11.3%); hand OA, 8.7% (7.5% to 9.9%); hip OA, 2.9% (2.3% to 3.6%); fibromyalgia, 1.7% (1.1% to 2.1%); spondyloarthritis, 1.6% (1.2% to 2.1%); gout, 1.3% (1.0% to 1.6%); rheumatoid arthritis, 0.7% (0.5% to 0.9%); systemic lupus erythaematosus, 0.1% (0.1% to 0.2%) and polymyalgia rheumatica, 0.1% (0.0% to 0.2%). After multivariable adjustment, participants with RMDs had significantly lower EQ5D scores (β=−0.09; p<0.001) and higher HAQ scores (β=0.13; p<0.001) than participants without RMDs. RMDs were also significantly associated with the presence of anxiety symptoms (OR=3.5; p=0.006). Conclusions RMDs are highly prevalent in Portugal and are associated not only with significant physical function and mental health impairment but also with poor HRQoL, leading to more health resource consumption. The EpiReumaPt study emphasises the burden of RMDs in Portugal and the need to increase RMD awareness, being a strong argument to encourage policymakers to increase the amount of resources allocated to the treatment of rheumatic patients.
Drug-related pneumonitis in patients with advanced renal cell carcinoma treated with temsirolimus.

PURPOSE Pneumonitis has occurred in patients treated with inhibitors of the mammalian target of rapamycin (mTOR). In a phase III study of patients with previously untreated, poor-prognosis, advanced renal cell carcinoma (ARCC), the mTOR inhibitor temsirolimus improved survival compared with interferon. We performed a retrospective, independent, blinded radiographic review of chest computed tomography (CT) images of patients in this study to characterize temsirolimus-related pneumonitis. PATIENTS AND METHODS Patients were treated with intravenous temsirolimus 25 mg once weekly or subcutaneous interferon alfa 3 million units, with an increase to 18 million units, thrice weekly. Drug-related pneumonitis was identified based on sequential chest CT images, required every 8 weeks, showing changes consistent with pneumonitis and not pneumonia (infection) or disease progression as correlated with clinical data. Cumulative probability of drug-related pneumonitis was estimated using the Kaplan-Meier method. RESULTS Eight (6%) of 138 and 52 (29%) of 178 evaluable patients on interferon and temsirolimus treatment, respectively, developed radiographically identified drug-related pneumonitis. Time to onset of pneumonitis was significantly shorter on the temsirolimus arm than on the interferon arm (log-rank P < .001). Estimated cumulative probability of pneumonitis at 8 and 16 weeks from first dose was 21% and 31%, respectively, on the temsirolimus arm and 6% and 8%, respectively, on the interferon arm. Respiratory symptoms were observed around time of onset of radiographically diagnosed temsirolimus-related pneumonitis in 16 (31%) of 52 patients. CONCLUSION Patients with ARCC receiving temsirolimus should be monitored closely for development of pneumonitis, and their management should be altered if clinical symptoms appear.
Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorectal adenocarcinoma.

PURPOSE PTK787/ZK 222584 (PTK/ZK; vatalanib), an orally active, multitargeted angiogenesis inhibitor, has shown tolerability and promising activity in early-phase studies, which led to a phase III trial in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4). PATIENTS AND METHODS Patients (N = 1,168) with previously untreated metastatic colorectal cancer were randomly assigned 1:1 to receive FOLFOX4 plus PTK/ZK or placebo (ClinicalTrials.gov identifier: NCT00056459). Stratification factors included WHO performance status (0 v 1 or 2) and serum lactate dehydrogenase (LDH; ≤ v > 1.5× the upper limit of normal). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and overall response rate (ORR). RESULTS PFS, OS, and ORR were not statistically improved with PTK/ZK (P > .05). Median PFS by central review was 7.7 months with PTK/ZK versus 7.6 months with placebo (hazard ratio [HR], 0.88; 95% CI, 0.74 to 1.03; P = .118); median OS was 21.4 months with PTK/ZK versus 20.5 months with placebo (HR, 1.08; 95% CI, 0.94 to 1.24; P = .260). In an exploratory post hoc analysis of PFS in patients (n = 158 per arm) with high serum LDH, a potential marker of hypoxia, PFS was longer with PTK/ZK versus placebo (7.7 v 5.8 months, respectively; HR, 0.67; 95% CI, 0.49 to 0.91; P = .009). CONCLUSION Although the efficacy objectives of this study were not met, a subgroup of patients who may potentially benefit from small-molecule vascular endothelial growth factor receptor inhibitor therapy has been identified and further research is warranted.
Performance of Conjugate and Zero-Forcing Beamforming in Large-Scale Antenna Systems

Large-Scale Antenna Systems (LSAS) is a form of multi-user MIMO technology in which unprecedented numbers of antennas serve a significantly smaller number of autonomous terminals. We compare the two most prominent linear pre-coders, conjugate beamforming and zero-forcing, with respect to net spectral-efficiency and radiated energy-efficiency in a simplified single-cell scenario where propagation is governed by independent Rayleigh fading, and where channel-state information (CSI) acquisition and data transmission are both performed during a short coherence interval. An effective-noise analysis of the pre-coded forward channel yields explicit lower bounds on net capacity which account for CSI acquisition overhead and errors as well as the sub-optimality of the pre-coders. In turn the bounds generate trade-off curves between radiated energy-efficiency and net spectral-efficiency. For high spectral-efficiency and low energy-efficiency zero-forcing outperforms conjugate beamforming, while at low spectral-efficiency and high energy-efficiency the opposite holds. Surprisingly, in an optimized system, the total LSAS-critical computational burden of conjugate beamforming may be greater than that of zero-forcing. Conjugate beamforming may still be preferable to zero-forcing because of its greater robustness, and because conjugate beamforming lends itself to a de-centralized architecture and de-centralized signal processing.
Spondylitis and Arthritis in Familial Mediterranean Fever

Hastalar ve yontemler: Kasim 2000 Mart 2012 tarihleri arasinda artrit veya inflamatuvar omurga agrisi yakinmasi ile basvuran ve AAA tanisi konmus 29 hastanin (12 erkek, 17 kadin; ort. yas 26.1±11.2 yil; dagilim 16-51 yil) verileri retrospektif olarak incelendi. Hastalarin yas ve cinsiyetleri kaydedildi. Artrit/spondilit baslangic yasi, AAA tani yasi, ailede AAA oykusu ve gecirilmis cerrahi girisim oykusu varliginin yani sira, periferik artriti bulunan hastalarin tutulan eklem sayisi ve yeri de kaydedildi. Sakroiliit ve spondiliti bulunan hastalarda periferik artrit varligi incelendi ve tedavide kullanilan ilaclar kaydedildi. Insan lokosit antijen (HLA)-B27 ve Akdeniz atesi (MEFV) geni analizi yapilmis hastalarin sonuclari kaydedildi.
Re-evaluation of serological criteria for early syphilis treatment efficacy: progression to neurosyphilis despite therapy

Objectives To study 17 cases of secondary syphilis that progressed to neurosyphilis despite appropriate treatments and whose rapid plasma reagin (RPR) titres showed a fourfold decrease within 6 months but did not revert to negative. Methods Secondary syphilis patients with the following criteria were analysed: (1) RPR titres declined fourfold within 3 months after therapy, (2) patients denied high-risk sexual behaviours following treatment, (3) RPR titre remained serofast 24 months after treatment, (4) reactive cerebrospinal fluid (CSF)–venereal disease research laboratory (VDRL) and CSF–Treponema pallidum Particle Agglutination Test (TPPA) and (5) HIV antibody negative. Results 14 male and three female patients met the criteria. 13 patients were asymptomatic. The CSF leucocyte count was elevated in 10 patients of whom nine also had elevated CSF–proteins. The RPR titres following secondary syphilis treatments were ≥1:32 in five cases, 1:16 in four cases, 1:8 in six cases and 1:4 in two cases. Following treatments for neurosyphilis, four cases with neurological or psychiatric manifestations resolved or improved, nine cases with raised CSF–white blood cells returned to normal and nine of 12 cases with raised CSF–protein declined to normal. Conclusions Neurosyphilis may be detected in immunocompetent patients despite appropriate therapy for early-stage syphilis and appropriate serological responses. Clinicians should consider a CSF examination in any treated patient with evidence of disease progression irrespective of prior treatment history and serological response.
Chlamydia trachomatis re-infections in a population-based cohort of women

Objectives Re-infection with chlamydia may increase subsequent reproductive morbidity in women. The authors sought to identify characteristics associated with re-infection. Methods A cohort of all women aged 10–49 years with a notification of genital chlamydia in the Australian state of New South Wales during 1999–2008 was defined. Probabilistic linkage was used to identify women with repeat notifications in the same period. The risk of repeat notification was examined according to age and other characteristics using proportional hazards regression. Results Among 40 936 women in the cohort, 3236 had at least one repeat chlamydia notification over an average of 3.5 years of follow-up. The incidence of repeat notification was greatest in the first year after index notification (4.5 per 100 person-years) and decreased thereafter. The RR of repeat notification increased by 8% (95% CI 7% to 9%) for each year decrease in age. Compared with women aged 20–21 years at index chlamydia notification, women aged <16 years were twice as likely to have a repeat notification (adjusted HR 2.12, 95% CI 1.75 to 2.56), while women aged 26–27 years were half as likely (adjusted HR 0.53, 95% CI 0.43 to 0.66). Year of index notification, parity and concurrent or past gonorrhoeal infection were also significantly associated with the risk of repeat notification, but socioeconomic status and area of residence were not. Conclusions Younger age is a strong predictor of chlamydia re-infection in women. The results support targeting interventions to prevent re-infections to very young women.
SOUTH AMERICAN COLUBRID ENVENOMATIONS

Most snakebites in South America are caused by pitvipers (Bothrops, Crotalus and Lachesis spp.) and coral snakes (Micrurus spp.), with less serious accidents caused by colubrids. Rear-fanged species are responsible for most colubrid envenomations, the principal genera involved being Clelia, Helicops, Liophis, Philodryas, Tachymenis, and Thamnodynastes. The hands, feet and upper and lower limbs are bitten most frequently. Most envenomations are mild, involving mainly local pain, edema and ecchymosis. Systemic envenomation (altered whole blood clotting time, systemic bleeding, shock, and renal failure) is rare and only one fatality suspected to have been caused by a colubrid (P. olfersii in Brazil) has been recorded. Treatment is symptomatic and supportive, and recovery is generally uneventful, with no sequelae. The similarity between the local effects of envenomations by colubrids and those produced by South American lanceheads (Bothrops spp.) has resulted in bothropic antivenom being administered in several cases, but there is little conclusive evidence that antivenom enhanced the patients' condition. Together, these findings indicate that envenomations by South American colubrids are considerably less serious than those reported for certain African and Asian colubrids (Boiga, Dispholidus, Rhabdophis and Thelotornis spp.). However, the limited number of species involved in human envenomations to date compared to the large number of South American colubrids currently recognized suggests the need for caution in generalizing about the potential seriousness of bites by species not yet implicated in such accidents.
SMS reminders improve re-screening in women and heterosexual men with chlamydia infection at Sydney Sexual Health Centre: a before-and-after study

Background In 2009, Sydney Sexual Health Centre implemented a short message service (SMS) reminder system to improve re-screening after chlamydia infection. SMS reminders were sent at 3 months recommending the patient make an appointment for a re-screen. Methods Using a before-and-after study, the authors compared the proportion re-screened within 1–4 months of chlamydia infection in women and heterosexual men who were sent an SMS in January to December 2009 (intervention period) with a 18-month period before the SMS was introduced (before period). The authors used a χ2 test and multivariate regression. Visitors and sex workers were excluded. Results In the intervention period, 141 of 343 (41%) patients were diagnosed with chlamydia and sent the SMS reminder. In the before period, 338 patients were diagnosed as having chlamydia and none received a reminder. The following baseline characteristics were significantly different between those sent the SMS in the intervention period and the before period: new patients (82% vs 72%, p=0.02), aged <25 years (51% vs 33% p<0.01), three or more sexual partners in the last 3 months (31% vs 27%, p<0.01) and anogenital symptoms (52% vs 38%, p<0.01). The proportion re-screened 1–4 months after chlamydia infection was significantly higher in people sent the SMS (30%) than the before period (21%), p=0.04, and after adjusting for baseline differences, the OR was 1.57 (95% CI 1.01 to 2.46). Conclusions SMS reminders increased re-screening in patients diagnosed as having chlamydia at a sexual health clinic. The clinic now plans to introduce electronic prompts to maximise the uptake of the initiative and consider strategies to further increase re-screening.
Informal confidential voting interviewing in a sexual risk assessment of men who have sex with men (MSM) and transgenders (hijra) in Bangalore, India

Objective The accuracy of self-reporting sensitive sexual risk behaviours is highly susceptible to misreporting. Informal confidential voting interviews (ICVIs) may minimise social desirability bias by increasing the privacy of the interview setting. The objective was to investigate determinants of risky behaviour among men who have sex with men (MSM) and ‘hijra’ (transgenders) reported through two interviewing tools: ICVIs and face-to-face interviews (FTFIs). Methods Cluster random sampling was used to recruit MSM in 85 cruising sites in Bangalore, including eight hammams (bath houses) and 77 public locations where MSM and hijra cruise for sex. Individuals were randomly allocated to one of the data collection methods(5 : 2 FTFI : ICVI). Data were analysed using standard regression and a profile regression approach that associates clusters of behaviours with our outcome (FTFI vs ICVI). Results A total of 372 MSM and hijra were interviewed for the FTFIs and 153 respondents completed ICVIs. Participants were more likely to report injecting drug use (4% vs 1%; p=0.008) and paying to have sex with a female sex worker (FSW) in the last year (28% vs 8%; p=0.001) in the ICVIs. There were no differences to questions on sociodemographics, sexual debut with another male, non-condom use (12% vs 14%), ever selling sex to men (58% vs 56%), current female partner (26% vs 20%) and non-condom use with a main female partner (17% vs 19%). Conclusions The significant differences between interview modes for certain outcomes, such as intravenous drug use and sex with a FSW, demonstrate how certain behaviour is stigmatised among the MSM community. Nevertheless, the lack of effect of the interviewing tool in other outcomes may indicate either less reporting bias in reporting this behaviour or environmental factors such as the interviewers not adequately screening themselves from the respondent or a potential disadvantage of using other MSM as interviewers.
Understanding trends in genital Chlamydia trachomatis can benefit from enhanced surveillance: findings from Australia

Objectives To determine trends and correlates of chlamydia positivity among young heterosexuals attending Australian sexual health services and to compare these with population-based notification data. Methods Data from 18 sexual health services and the national notification scheme were analysed. A χ2 test assessed trends in chlamydia positivity among young heterosexuals tested from 2006 to 2010, and logistic regression was used to determine correlates of positivity. Nucleic acid amplification tests were used throughout the study period. Results During 2006–2010, 64 588 heterosexuals aged 15–29 years attended the sexual health services for the first time and the annual chlamydia testing rate was consistently >80%. Overall, chlamydia positivity increased by 12%, by 8.3% in heterosexual men (from 13.2% in 2006 to 14.3% in 2010; p-trend=0.04) and by 15.9% in women (from 11.3% in 2006 to 13.1% in 2010; p-trend<0.01). Independent correlates of chlamydia positivity in sexual health service patients were being aged 15–24 years, residing in a regional/rural area, being Aboriginal and/or Torres Strait Islander, being a non-Australian resident and attending in 2010 compared with 2006. Over the same period, the population-based notification rate increased by 43% against a background of a >100% increase in testing. Conclusions The sexual health service network suggests a moderate increase in chlamydia prevalence in young heterosexuals tested at sexual health services, in contrast to the steep increase shown by notifications. This highlights the caution needed in interpreting chlamydia trends without a corresponding testing denominator.
Thromboprophylaxis and obstetric management of the antiphospholipid syndrome

There is consensus in treating patients with antiphospholipid syndrome (APS) and first venous thrombosis with oral anticoagulation to a target international normalized ratio of 2.0 – 3.0. A recent systematic review recommended a target international normalized ratio > 3.0 in the group of patients with APS and arterial thrombosis. The approach for women with obstetric manifestations of APS is based on the use of aspirin plus heparin. In addition, we summarize the evidence-based information about management of catastrophic APS and some difficult cases, such as ‘seronegative’ APS, patients who do not display formal classification criteria for APS, and recurrent thrombotic events despite optimal anticoagulation.