Evaluation of degarelix in the management of prostate cancer

Medical castration using gonadotropin-releasing hormone (GnRH) receptor agonists currently provides the mainstay of androgen deprivation therapy for prostate cancer. Although effective, these agents only reduce testosterone levels after a delay of 14 to 21 days; they also cause an initial surge in testosterone that can stimulate the cancer and lead to exacerbation of symptoms (“clinical flare”) in patients with advanced disease. Phase III trial data for the recently approved GnRH receptor blocker, degarelix, demonstrated that it is as effective and well tolerated as GnRH agonists. However, it has a pharmacological profile more closely matching orchiectomy, with an immediate onset of action and faster testosterone and PSA suppression, without a testosterone surge or microsurges following repeated injections. As a consequence, with this GnRH blocker, there is no risk of clinical flare and no need for concomitant antiandrogen flare protection. Degarelix therefore provides a useful addition to the hormonal armamentarium for prostate cancer and offers a valuable new treatment option for patients with hormone-sensitive advanced disease. Here, we review key preclinical and clinical data for degarelix, and look at patient-focused perspectives in the management of prostate cancer

Chemoprevention of prostate cancer with nutrients and supplements

As the adult population is increasing, prostate cancer (PCa) will become a considerable health problem in the next millennium. This has raised public interest in potential chemoprevention of this disease. As PCa is extremely common and generally slow to progress it is regarded as an ideal candidate for chemoprevention. At present, the 5 alpha-reductase inhibitors finasteride and dutasteride have been identified as preventive agents. This review describes whether selenium, alpha-tocopherol, isoflavones, lycopene green tea polyphenols, calcium, and resveratrol may be useful for decreasing the risk of PCa in men. Although encouraging results are present, some studies show negative results. Differences in study design, sample size, dose administered, and/or concentrations achieved in the body may be the reason for these inconsistencies. Today, chemopreventive agents may be appropriate for high-risk patients like those with high-grade prostatic intraepithelial neoplasia and other high-risk groups such as patients with elevated prostate specific antigen (PSA) and negative biopsy, rapid PSA velocity, and with a family history of PCa. Although larger randomized controlled studies are needed and epidemiologic evidence should be placed in a clinical context, physicians must be aware of these preventive opportunities in PCa care. Combinations of chemopreventive agents should be carefully investigated because mechanisms of action may be additive or synergistic

Diffusion of a Social Norm: Tracing the Emergence of the Housewife in the Netherlands, 1812-1922

The emergence of the housewife in the Netherlands over the period 1812-1922 was strongly influenced by the social norm that women should withdraw from the labour market on the eve of marriage. Adherence to this norm is most clearly reflected in the emergence of the housewife among the lower classes, especially at the close of the nineteenth century among wives of farmers. Women in urban municipalities, however, set the norm far earlier and differences across social classes were signif

Імітація монаршної поведінки в “дивних” вчинках Богдана Хмельницького на початку 1649 р.

Увага до постаті Богдана Хмельницького як на фаховому, так і на дилетантському рівні не вщухає вже, навіть попри періодичні офіційні чи неофіційні заборони, протягом трьох з половиною століть. Політичні та ідеологічні чинники, як можна спостерігати останні півтора десятиліття в Україні та, частково, у Польщі, регулярно посилюють інтерес до біографії гетьмана, його вчинків, наслідків діяльності, супроводжуючись, як нерідко трапляється в аналогічних ситуаціях, створенням зі складної, протирічливой, трагічної постаті Б.Хмельницького національного ідола, усі дії якого набувають містичного, пророчого, апріорно історично-виправданого характреру. Концептуальні трагічні помилки, прорахунки, прояви некомпетентності, невиправданої навіть за поняттями тієї епохи жорстокості переважно «делікатно» замовчуються, у кращому разі – обмежуються легкими докорами, а здебільше - пояснюються «злочинною змовою» сучасників-поляків, які свідомо з метою дискредитації сфальсифікували вчинки гетьмана, перебільшивши закономірні для усіх війн трагічні складові україно-польської війни. Як не парадоксально, до сьогодні залишаються, на жаль, поодинокими спроби дати добре аргументоване, позбавлене соціологічних та психологічних штампів, пояснення тих чи інших вчинків Б.Хмельницького та його соратників (як, власне, і представників польського, татарського, російського та турецького таборів), яке б базувалося не на упередженому заздалегідь виправдальному чи звинувачувальному ставленні до подій середини XVII ст., а на підгрунті максимально повного врахування ментальних, поведінкових стереотипів доби. Ми маємо на увазі вишукано-резонансну рецензію Н.Яковенко на серію публікацій перш за все В.Смолія та В.Степанкова [17; див. також: 19], а також деяких інших авторів, зокрема О.Толочка [11] та автора цих рядків [2], присвячених політичній та духовній ситуації в Україні напередодні Хмельничини, українській національній революції та постаті Хмельницького. Для наших подальших роздумів немає особливої потреби здійснювати розлогий джерелознавчий та історіографічний аналіз, оскільки він, з одного боку, вимагає спеціальної концептуальної зосередженості, а з іншого - надалі ми будемо оперувати у необхідних випадках виключно загальновідомими, хрестоматійними аргументами, коли можна дозволити собі уникнути розлогих екскурсів щодо розгляду джерел та літератури. Зазначимо лише, що безпосередньо біографії Б.Хмельницького присвячена досить велика кількість робіт з різних наукових та ідеологічних таборів, серед яких в першу чергу слід назвати імена М.Грушевського, М.Кордуби, В.Липинського, І. Крип’якевича, В.Замлинського, Я.Дашкевича, В.Смолія, В.Степанкова, П.Гоя, Я.Федорука, В.Горобця, Т.Чухліба, В.Сергійчука, В.Серчика та багатьох інших. Події кінця 1648 – початку 1648 рр. з огляду на їх особливу роль в контексті подій українських визвольних змагань і які будуть нас цікавити в першу чергу

A Moral Dilemma for the Political Psychologist: Decreasing Criminal Violence as Symptom

This article describes two approaches to decreasing criminal violence and the moral dilemma in choosing between them

Hypofractionated intensity modulated irradiation for localized prostate cancer, results from a phase I/II feasibility study

<p>Abstract</p> <p>Background</p> <p>To assess acute (primary endpoint) and late toxicity, quality of life (QOL), biochemical or clinical failure (secondary endpoints) of a hypofractionated IMRT schedule for prostate cancer (PC).</p> <p>Methods</p> <p>38 men with localized PC received 66 Gy (2.64 Gy) to prostate,2 Gy to seminal vesicles (50 Gy total) using IMRT.</p> <p>Acute toxicity was evaluated weekly during radiotherapy (RT), at 1–3 months afterwards using RTOG acute scoring system. Late side effects were scored at 6, 9, 12, 16, 20, 24 and 36 months after RT using RTOG/EORTC criteria.</p> <p>Quality of life was assessed by EORTC-C30 questionnaire and PR25 prostate module. Biochemical failure was defined using ASTRO consensus and nadir+2 definition, clinical failure as local, regional or distant relapse.</p> <p>Results</p> <p>None experienced grade III-IV toxicity. 10% had no acute genito-urinary (GU) toxicity, 63% grade I; 26% grade II. Maximum acute gastrointestinal (GI) scores 0, I, II were 37%, 47% and 16%. Maximal acute toxicity was reached weeks 4–5 and resolved within 4 weeks after RT in 82%.</p> <p>Grade II rectal bleeding needing coagulation had a peak incidence of 18% at 16 months after RT but is 0% at 24–36 months. One developed a urethral stricture at 2 years (grade II late GU toxicity) successfully dilated until now. QOL urinary symptom scores reached a peak incidence 1 month after RT but normalized 6 months later. Bowel symptom scores before, at 1–6 months showed similar values but rose slowly 2–3 years after RT. Nadir of sexual symptom scores was reached 1–6 months after RT but improved 2–3 years later as well as physical, cognitive and role functional scales.</p> <p>Emotional, social functional scales were lowest before RT when diagnosis was given but improved later. Two years after RT global health status normalized.</p> <p>Conclusion</p> <p>This hypofractionated IMRT schedule for PC using 25 fractions of 2.64 Gy did not result in severe acute side effects. Until now late urethral, rectal toxicities seemed acceptable as well as failure rates. Detailed analysis of QOL questionnaires resulted in the same conclusion.</p

Uro-oncology in the era of social distancing : the principles of patient-centered online consultations during the COVID-19 pandemic

The COVID-19 pandemic poses significant challenges to healthcare facilities and as per social distancing measures, many consultations are now being carried out via means of telemedicine. As some urologists may not be skilled with remote consultations, there is a need for recommendations on patient-centered online medical counseling. We have identified eight areas of excellence and defined the principles based on our experience. A professional setting should be provided, in which the privacy of the patient can be ensured. Accompanying persons should be encouraged into the consultation. Proper introduction could serve not only to verify the personality of the patient, but also to provide them with a sense of confidentiality. The interview should be held in a way to overcome the limitations of non-physical encounters, and pande-mic-specific issues should be taken into consideration. When arranging plans, the physician should judge accordingly in regards to what type of management is inevitable or safe, as well as available at this point; strict follow-up should be arranged. As home isolation may lead to unfavorable changes in lifestyle, this issue should be addressed too. The patient should be guided on how to self-educate. Concluding the visit should be aimed at proper evaluation of the patient's comprehension of the consultation. It is vital to pursue consistency in providing care to patients. While online counseling may seem challenging, if one adheres to the principles of patient-centered practice, telemedicine may become a valuable tool in maintaining the best-quality care amid the ongoing pandemic

Thermal study of the effect of several solvents on polymerization of acrylonitrile and their subsequent pyrolysis

The polymerization of acrylonitrile to polyacrylonitrile (PAN) has been studied using several solvents: N,N-dimethylformamide (DMF), hexane, toluene, water, and in bulk form (no solvent). The addition of DMF is the only case where both monomer and polymer are soluble in the solvent. Thermal analyses of the resultant products after polymerization have been performed by differential scanning calorimetry and pyrolysis–gas chromatography: mass spectrometry. The effect of the solvents employed as media for polymerization is interpreted from the results of the thermal and structural (X-ray diffraction) methods. The polymer samples obtained when using water or toluene as solvents have the greater content of amorphous components compared to the others. The amide molecules are difficult to completely eliminate in the product obtained after the polymerization reaction and even after prolonged heating at 110°C and remain occluded. DMF can be considered to exert a plasticized effect on PAN and is even capable of forming complexes by dipolar bonding. As a result of this interaction, the thermogram is quite different from the other samples studied in the present work, showing a single sharp exothermic peak. This is associated with nitrile group polymerization (cyclization) of PAN. It is deduced that the amount of heat evolved as well as the temperature interval over which it is released are influenced by the chemical processing of PAN, in particular when using DMF as solvent for both monomer and polymer. Pyrolysis of the different PAN samples revealed the release of occluded solvent molecules, mainly when using DMF, and compounds produced from the thermal degradation processes. Different types of cyclized compounds, such as pyridine derivatives and aromatic nitriles were identified. All these compounds could be derived from cyclized PAN structures which are not completely degraded by the thermal treatment of pyrolysis. Alkyldinitriles have also been tentatively identified associated with the final molecular breakdown of cyclized structures with six-member rings by pyrolysis. Valuable complementary information on the structure of the PAN samples (homopolymer) obtained using the different processing approaches involving several solvent media has been provided by pyrolysis. The present results will improve our understanding of the evolution of the structure and properties of carbon and activated carbon fibres which will enable us to establish processing strategies in order to obtain these materials under adequate and reproducible conditions.Peer reviewe

Conflict of Evidence:Resolving Discrepancies When Findings from Randomized Controlled Trials and Meta-analyses Disagree

Financial disclosures: Richard J. Sylvester certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None.Peer reviewedPostprin

Comparison of functional outcome after extended versus super-extended pelvic lymph node dissection during radical prostatectomy in high-risk localized prostate cancer

Background: Urinary continence and erectile function (EF) are best preserved whenmeticulous dissection of prostate and nerve sparing technique are used during radicalprostatectomy (RP). However, extent of lymph node dissection (LND) may also adverselyaffect functional results.Objective: To determine whether performing a super-extended LND (seLND) has asignificant effect on recovery of urinary continence and EF after RP.Design, setting, and participants: All patients who underwent RP from January 2007until December 2013 were handed questionnaires assessing continence and EF. Allpatients in whom at least an extended LND (eLND) was performed were selected. Thissearch yielded 526 patients. 172 of these patients had filed out 2 or more questionnairesand were included in our analysis.Outcome measurements and statistical analysis: All questionnaires were reviewed.We used Kaplan–Meier analyses and multivariate Cox analysis to assess the differencein recovery of continence and EF over time for eLND/seLND. Primary endpoints were fullrecovery of continence (no loss of urine) and full recovery of EF (successful intercoursepossible). Patients who did not reach the endpoint when the last questionnaire was filledout were censored at that time. Median follow-up was 12.43 months for continence, and18.97 months for EF.results and limitations: Patients undergoing seLND have a lower chance of regainingboth urinary continence [hazard ratio (HR) 0.59, 95% CI 0.39–0.90, p = 0.026] and EF(HR 0.28, 95% CI 0.13–0.57, p = 0.009). Age at surgery had a significant influence onboth continence and EF in multivariate analysis. Major limitation of the study was that noformal preoperative assessment of continence and potency was done.conclusion: Extending the LND template beyond the eLND template may cause atleast a significant delay in recovery of urinary continence and leads to less recovery of EF.</p