By: Keith A. Hecht, PharmD, BCOP
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Lipid-rich diets stimulate mesangial cell proliferation and enhance glomerulosclerosis as a result of medications related to the integumentary system cheap meclizine 25mg fast delivery deposition of lipid and accumulation of froth cells in the mesangial areas (Song medications like zovirax and valtrex cheap 25 mg meclizine amex, Li et al symptoms 9 days past iui discount 25 mg meclizine otc. They contain haem and are able to catalysing numerous reactions including hydroxylation medications dialyzed out purchase meclizine 25mg with amex, peroxidation, sulfoxidation, N-oxidation, epoxidation, deamination and desulfuration (Lisurek and Bernhardt 2004, Hille, Hu et al. The steroidogenic pathways within the adrenal cortex are illustrated in Figure 1-10 and Figure 1-11. This microsomal enzyme acts on both pregnenolone or progesterone; their 17derivatives are then subject to additional conversions to type cortisol. Low intravascular blood quantity (and due to this fact stress) prompts renin exercise (secreted from renal juxtaglomerular kidney cells) and conversion of angiotensinogen to Angio I. Increased extracellular K+ concentration depolarises the cell membrane, opening voltage-dependent Land T-kind Ca2+ channels. Serotonin can also be a weak stimulator of aldosterone synthesis; the serotonin precursor, 5-hydroxytryptophan will increase plasma aldosterone while serotonin antagonist reduces it (Shenker, Gross et al. Adipose cells secrete several merchandise of linoleic acid oxidation and other secretagogues that stimulate aldosterone manufacturing (Goodfriend, Ball et al. The biggest distinction between the genes lies in their 5� untranslated areas, accounting for the variations in their expression (Mornet, Dupont et al. This polymorphism has been considerably associated with altered blood stress and aldosterone ranges (White and Slutsker 1995). Davies et al (1999) reported that the T-allele at -344 happens more frequently in hypertensive sufferers and associates with considerably larger ranges of aldosterone metabolite (tetrahydroaldosterone) in the urine compared to -344C groups (Davies, Holloway et al. More just lately, evaluation means that rs1799998 is 59 not itself a functional polymorphism (Niu, Guo et al. Adrenal failure (Addison�s illness) disrupts each electrolyte and power metabolism and, without therapy, is fatal. The results of excess cortisol or aldosterone have already been described and are equally debilitating. These extreme conditions are uncommon, comprising principally adrenocortical neoplasia and monogenic issues of specific enzymes� gene expression. Recent studies, nevertheless, suggest that small deviations from normal gene expression, when sustained over a lifetime as the results of, for instance, polymorphic variation or modifications in regulatory components, may be necessary and customary determinants of well being. Mutation of K+ channels can alter the selectivity filters to K+, making them non-selective channels (Heginbotham, Lu et al. In the resting state, zona glomerulosa cells have negative resting potentials and steroidogenesis stays inactive (Guagliardo, Yao et al. This causes membrane depolarization and voltage-dependent Ca2+ channels to open, rising Ca2+ influx and stimulating the calcium-calmodulin pathway. The mutation of this gene is predicted to enhance intracellular Ca2+ concentration and enhance aldosterone synthesis (F. The Wnt/ catenin is necessary in embryonic development and cell renewal (Berthon, Sahut-Barnola et al. In uncommon instances, mutation of gene could cause severe abnormalities and result in hypertension. There are widespread scientific signs that relate to genetic abnormalities as proven Table 1-three. The majority have an effect on electrolyte transport on the distal tubule, instantly or not directly, by altering mineralocorticoid secretion. Monogenic issues share several widespread ultimate mechanisms: they escalate sodium and chloride reabsorption on the distal nephron, trigger plasma quantity expansion and reduce plasma renin exercise (Garovic, Hilliard et al. Monogenic hypertension can current with severe hypertension, early onset (although not at all times) and sometimes with a constructive household history. Smaller however nonetheless vital variations in the exercise of those techniques may exist to a wide extent in the general population. Identification of specific areas of the chromosome linked to a monogenic trait in hypertension may be carried out utilizing linkage evaluation by genotyping (Padmanabhan, Caulfield et al. Table 1-5: Selected linkage studies in hypertension Study Chromosomal Participant Region (Pan, Chen et al. They are estimated to regulate the transcription of roughly 30% of the human protein-coding genome. This deaminase catalyses conversion of adenosine nucleotides to inosine in an editing course of often known as A-to-I (Luciano, Mirsky et al. Dicer has 2 major domains, Cterminal and N-terminal, which every have specific properties and capabilities (Figure 1-17). The percentage will increase to nearly 50% if the space threshold is about at 10000 nt. The correlation of expression is reduced considerably if this distance exceeds 50 kb. However, it may also be detected extracellularly, notably in the blood (Valadi 2007, Pegtel, Cosmopoulos et al. Aldosterone excess will increase cardiovascular morbidity and mortality impartial of elevated blood stress. Romero et al confirmed that miR-21 will increase aldosterone secretion (Romero, Plonczynski et al. Miravirsen targets the stem construction of miR-122 precursors and disrupts the processing of pri-122 and pre-miR-122 by inhibiting Drosha and Dicer (Gebert, Rebhan et al. It stimulates G1 cell cycle arrest, senescence, apoptosis and acts as a tumour silencer because of the irregular CpG methylation ninety one of its promoter (Lodygin, Tarasov et al. The study adopted the standard protocol for oncology study design with two phases: dose-escalation and enrichment (Christoph 2013). The purpose was to restore normal endogenous mir-122 tumour suppressor function (Bouchie 2013). Each has its own distinctive tradition conditions and slight variations in their characteristics (Wang and Rainey 2012). The supernatant was removed and the cell pellet was re-suspended in new full development medium and aliquoted into a brand new flask (T150). Cell suspensions were then aliquoted and transferred to cryovials and frozen at -80oC utilizing isopropanol and Nalgene CryoContainer (Thermo Fisher Scientific, Loughborough, U. The cell suspension in the vial was aliquoted to a universal container with 10 ml contemporary development medium. The cell pellet was then resuspended with 5 ml contemporary medium and transferred to a T25 flask (Corning) and cultured as described in part 1. The cell pellet was resuspended with 10 ml medium and 20 l of this cell suspension positioned on the haemocytometer under a coverslip, utilized by capillary motion across the chamber. The variety of cells was assessed under a lightweight microscope by counting and averaging the variety of cells in every 1mm square. For a 6-well plate, 5 x one hundred and five cells were added to every well, while for 24-well plates, eight x 104 cells were added. Later, medium was removed and changed with full development medium also containing the related factor and incubated at 37�C for an extra zero, 6, 12 or 24 hours, as required. Later, transfection reagent grasp combine was prepared by mixing eight l of Lipofectamine 2000 transfection agent (Ambion Life Technologies, Paisley, U. Using 6-well plates, the cells were diluted to a concentration of two x one hundred and five/ ml utilizing contemporary medium and the suspension was incubated at 37�C till required. A) is used to assess cell proliferation, utilizing a colorimetric technique to decide the variety of proliferating viable cells. Using 96-well plates, the absorbance of the formazan may be measured instantly at 490 nm. The plate was incubated at 37�C for 1 to four hours, with the colorimetric response progress being measured after 1, 2,three and four hours of incubation on the plate reader. After 2-24 hours of BrdU incubation, fixative/denature resolution was added to cells. BrdU Label dilution was prepared by adding the label to tradition medium in 1:2000 ratio. The BrdU Label was then removed and 800 l Fixative/ Denaturing Solution added to every well and left for half-hour at room temperature. All liquid was removed from the well and one hundred x Anti-BrdU Antibody 1:one hundred in Antibody Dilution Buffer resolution was prepared.
Late reconstruction (after 6-eight technique of restore in main and early repairs 300 medications for nclex purchase 25 mg meclizine overnight delivery, whereas weeks) is suggested treatment of bronchitis meclizine 25mg without prescription, often with hepatico-jejunostomy Roux-en-Y hepaticojejunostomy is the same old surgical remedy (low quality evidence; weak recommendation) for delayed restore [489] medicine 4h2 effective 25 mg meclizine. Another price-effectiveness study concluded that early bile duct restore by specialist surgeons was cheaper than delayed bile duct restore medications cause erectile dysfunction discount meclizine 25mg with visa, whereas main restore by the non-specialist was the least price-efficient option based mostly on observational collection [490]. What is the recommended remedy for postoperatively the long-term results of hepaticojejunal anastomoses are established bile duct accidents Local an infection or sepsis is an independent threat issue for a poor results of the early surgical Bile duct lesions types A, B or C must be treated reconstruction [493]. Mortality in sufferers with bile duct injury endoscopically; late surgical remedy is the recommended throughout cholecystectomy is higher than in these present process remedy for sort D injury (low quality evidence; weak recommendation) cholecystectomy without bile duct injury after 1 year (4% vs. Health-related quality of life after bile duct restore is variable with some studies reporting similar quality of life in sufferers who had undergone surgical reconstruction, whereas others Comment: the right prognosis and classication of bile duct reporting poorer quality of life in those who had bile duct injury injury is of nice importance for the selection of remedy. A comseveral years after corrective surgical procedure as in comparison with those who parison of the literature knowledge is difficult due to using vardid not have bile duct injury [494]. The Amsterdam classication [486] is usually used (Table 1), since Persistent biliary signs after cholecystectomy on this scheme classication could be immediately linked to the remedy. After classication of the injury, the patient must be referred to a specialized middle with a multidisciplinary expertise group. How are persistent signs after cholecystectomy In case of intraoperatively recognized bile duct lesion, reclohandled Otherwise merely cholangiopancreatography must be thought-about in the diagnostic analysis of publish cholecystectomy sufferers with biliary signs (low quality evidence; Table 1. It might be difficult to differentiate the complaints after cholecystectomy, typically after a brief pain from that brought on by gallbladder stones. Bile after cholecystectomy due to the presence of intrahepatic sludge duct obstruction is usually followed by complications, similar to and microliths, or recurrent bile duct stones (see part Prevenjaundice and cholangitis. These latter cholestatic liver biochemical tests progressively enhance with the length and severity of biliary obstruction. The pain is situated in the (reasonable quality evidence; robust recommendation) right upper stomach quadrant or the epigastrium, lasts more 16 Journal of Hepatology 2016 vol. It also evaluates different possible causes of upper stomach pain and gallstone complications however is associated with a signicant radiComment: In 4�eight% of the sufferers with gallbladder stones, ation dose. Diagnosis of acute cholangitis Gallstone migration, even of small stones, is usually preceded by a interval of biliary obstruction [540]. Comment: Acute cholangitis could be identified by the presence Patients with pancreatitis or obstructive jaundice have more of the Charcot�s triad, i. Its sensitivparameters often enhance throughout the rst hours following the ity reaches one hundred% and specicity is 95%, resulting in an accuracy of pain attack. In excessive threat circumstances (see recommendation: Is Endoscopic sphincterotomy and stone extraction is a main closure preferred over T-tube drainage throughout surgical recommended remedy of bile duct stones bile duct exploration Therefore, endoscopic stone removing is at present the pre(reasonable quality evidence; robust recommendation) ferred method in most nations. Two trials (one in sufferers with In case of failed normal stone extraction, extracorporeal gallstone pancreatitis) indicate fewer endoscopic procedures shock wave, electrohydraulic or laser lithotripsy could also be performed (low quality evidence; weak recommendation). In the case of failed endoscopic therapy, cholecystectomy mixed with bile duct What are the best forms of remedy for bile duct stones exploration or intraoperative endoscopic retrograde when detected intraoperatively or postoperatively Therefore, the final consensus is that symptomatic choledocholithiasis must be treated. The natural Comment: When bile duct stones are detected in the course of the historical past of asymptomatic choledocholithiasis seems more operation, transcystic stone extraction could be tried, if the benign. Nevertheless, greater than 25% of sufferers seem to surgeon is skilled on this process. Transcystic stone develop (often serious) complications throughout follow-up extraction is secure, and success price is approximately 75%. In the final decades, there has been an increasing role except in centers of experience [564�566]. Upon postoperative for the endoscopic remedy (sphincterotomy and stone extracdiagnosis of bile duct stones, endoscopic sphincterotomy and tion) of bile duct stones. Performance of a minimum of one hundred procedures Is main closure preferred over T-tube drainage throughout annually is associated with higher consequence, whereas patient surgical bile duct exploration Endoscopic papillary balloon dilatation with a big diameter In case of surgical bile duct exploration, main closure balloon (12�20 mm) represents an option to facilitate the extracmay be preferred over T-tube drainage in low threat circumstances tion of huge stones [553,554]. Anaerobic bacteria are normally isolated in conjunction with cardio bacteria, rather than a sole isolate from bile, and infrequently in the setting of previous bile duct instrumentation When ought to cholecystectomy be performed in sufferers with and a more severe clinical condition. There is a clear difference gallbladder stones after endoscopic removing of bile duct between results of bile cultures in comparison with associated blood stones Bile cultures are positive in eighty�one hundred%, and blood cultures in 20�60% of sufferers with cholangitis. Streptococcus In sufferers with simultaneous gallbladder and bile duct and Enterococcus species are infrequently and anaerobic bacteria stones, early laparoscopic cholecystectomy must be are not often cultured from blood. Empirical antibiotic therapy that features coverage of the cardio gram-negative bacteria and anaerobic bacteria must be thought-about till the results of bile cultures and blood cultures are available. The length of Comment: See part: Patients with simultaneous gallbladantibiotic therapy will depend on severity of the clinical condider and bile duct stones tion at presentation, whether blood cultures have been positive and recovery after biliary drainage. Treatment of acute cholangitis Most cholangitis sufferers will reply satisfactorily to initial conservative therapy with broad spectrum antibiotics. Although these sufferers might get elective biliary decompression and stone removing, it seems sensible to obtain biliary decompression in all How ought to sufferers with acute cholangitis be treated Urgent decompression (reasonable quality evidence; robust recommendation) must be thought-about in case of severe cholangitis not responding to uid resuscitation and intravenous antibiotics. Consensus criTiming of biliary decompression is dependent upon severity of the teria for dening severity of cholangitis have been revealed cholangitis and effects of medical therapy including [572]. Results of endoscopic therapy for severe cholangitis not responding to fluid resuscitation and acute gallstone cholangitis have been superior to surgical remedy, intravenous antibiotics (low quality evidence; each in retrospective and potential randomized trials weak recommendation) [269,573]. It is smart to aspirate contraindications to endoscopic therapy, percutaneous bile bile after bile duct cannulation before contrast injection, in duct drainage is the process of alternative order to avoid elevated bile duct stress and bacteremias. In secure sufferers, sphincterotomy with stone extraction could be performed in the course of the initial process. First line remedy ought to include general supportive In case of signicant coagulation disturbances, giant and measures including enough intravenous hydration and antibimultiple stones, or unstable sufferers, nasobiliary drain placeotics, that are required in the rst hour after hospital admission ment or biliary endoprostheses are preferred as initial treatin case of sepsis [569]. Nasobiliary and endoprosthesis are equally efficient contaminated bile, broad spectrum antibiotics must be utilized. Nevertheless, endoprosthesis alternative of antibiotic coverage is dependent upon cholangitis severity must be preferred since this is much less uncomfortable for the and native antimicrobial resistance patterns. In fact, sufferers with biliary pancreatitis depending on the severity of cholangitis however preferably inside often exhibit such small stones [241,615]. While Comment: It is outside the scope of this guideline to focus on laparoscopic cholecystectomy has generally been performed after acute pancreatitis intimately, however some aspects of endoscopic treatthe acute signs resolve and the serum amylase actions ment are talked about. There have been convention is recommended, preferably inside 24 h [538,578�580]. Waiting as much as seventy two h permits not responding to uid resuscitation and intravenous antibiotics. However, in case of predicted severe pancreatitis, the numno denite recommendations could be made relating to the timing ber of included sufferers in the meta-analysis was too small to of cholecystectomy in sufferers with acute severe pancreatitis, draw denite conclusions. Delayed not only bile duct stones, but also the peripancreatic edema can laparoscopic cholecystectomy could decrease the conversion to trigger biliary obstruction [356]. Nevertheless, the course of open cholecystectomy since the inammation and uid 20 Journal of Hepatology 2016 vol. Surgical down or turn into nicely-dened pseudocysts in the course of the ready resection must be thought-about for sufferers with unilateral stone time. Disadvantages of delayed laparoscopic cholecystectomy illness, significantly if biliary strictures and/or lobar atrophy are are potential recurrence of biliary signs and prolonged hosalso current [635,636]. Nevertheless, it seems sensible to postpone cholestone clearance charges higher than eighty% and fewer recurrences than cystectomy in sufferers with severe biliary pancreatitis with endoscopic modalities [637�639]. Cholecystectomy resonance cholangiopancreatography the second is indicated in the case of symptomatic gallbladder stones or (very low quality evidence; weak recommendation) sludge [216]. Biliary drainage or partial hepatectomy could also be indicated in the case of symptomatic intrahepatic bile duct dilation lled with stones. Ascending cholangitis is a frequent acute complication associated with hepatolithiasis, and persistent complications Therapy of gallbladder stones throughout being pregnant include secondary biliary cirrhosis, segmental or lobar atrophy, liver abscess, and cholangiocarcinoma. Comment: Gallbladder sludge or gallstones develop in 5% of pregnant women each, however only one. Of note, a randomized intervention to made individually for each patient and interdisciplinarily for enhance bodily activity (from 15.
Of the 732 candidate genes analyzed medicine prices buy cheapest meclizine, 288 (39%) have been found to symptoms 9 days after ovulation order 25 mg meclizine mastercard predict scientific recurrence despite heterogeneity and multifocality treatment viral conjunctivitis buy meclizine 25mg, and 198 (27%) have been predictive of aggressive illness after adjustment for prostate-specific antigen treatment enlarged prostate cheap meclizine 25 mg online, Gleason score, and scientific stage. Clinicopathological knowledge, Genomic Prostate Score results and therapy associated information have been retrieved from medical data. Data additionally have been collected for a pre-Genomic Prostate Score baseline group recognized from May 2012 to April 2013. Descriptive analyses have been carried out to consider the proportion of men for whom active surveillance was beneficial and used before and after the provision of Genomic Prostate Score. Overall 15 physicians contributing 211 sufferers (Genomic Prostate Score group 124, baseline group 87) participated within the chart evaluate. With Genomic Prostate Score the relative improve in active surveillance beneficial was 22% (baseline 50% and Genomic Prostate Score 61%, absolute improve of eleven%) and the relative improve in use of active surveillance was 56% (baseline 43% and Genomic Prostate Score 67%, absolute improve of 24%). Treatment recommendations for active surveillance have been directionally according to assay reported threat. The relative improve in recommendations for active surveillance was 24% (absolute change forty one% to 51%). The space under the receiver 184/512 Tumor Markers Medical Clinical Policy Bulletins | Aetna operating characteristic curve improved from zero. The study was carried out at a single giant urology group apply and enrolled sufferers with a single insurance coverage service. Oncotype Dx Prostate testing improves health outcomes within the investigational setting. The evaluation acknowledged: Published proof is sparse and insufficient to draw conclusions on the. Also, the necessity for tissue which has previously been mounted for histological evaluation is of some concern. European Association of Urology (2015) prostate most cancers pointers state that genomics on the tissue samping appear "promising," however "further study knowledge will be wanted before such markers can be used in commonplace scientific apply. Although full evaluation of their scientific utility requires prospective, randomized scientific trials, which are unlikely to be carried out, the panel believes that men with clinically localized illness might contemplate the use of tumor-based mostly molecular assays at this time. Future comparative effectiveness research might allow these tests and others like them to gain extra proof concerning their utility for higher threat stratification of men with prostate most cancers. Although full evaluation of their scientific utility requires prospective, randomized scientific trials, which are unlikely to be carried out, the panel consider that men with low or favorable intermediate threat illness might contemplate the use of Decipher, Oncotype Dx Prostate, Prolaris, or ProMark throughout initial threat stratification. The pointers state that the Oncotype Dx Prostate test has not been validated as providing substantial benefit within the active surveillance population. These investigators reported on outcomes within the first 297 sufferers enrolled within the study with valid 17-gene assay results and decisionchange knowledge. Secondary end-points included perceived utility of the assay and 188/512 Tumor Markers Medical Clinical Policy Bulletins | Aetna patient decisional conflict before and after testing; 1-yr results have been out there on 258 sufferers. Shift between initial recommendation and shared determination occurred in 23 % of sufferers. This study was based mostly on an interim evaluation of the first 297 sufferers enrolled in a big (n = 1,200), multi-heart prospective trial, and will thus be thought-about preliminary. Another drawback of the study was that sufferers have been treated throughout an era when definitive therapy was commonplace of care with little adoption of active surveillance. First, some sufferers followed to 6 months had no comply with-up knowledge at 12 months, which may be as a result of sufferers looking for care elsewhere, an insurance coverage change, or a small threat of mortality between 6 and 12 months. Charts from 6 months post-biopsy have been reviewed for each cohorts to evaluate administration obtained within the untested and tested cohorts. Patient traits have been typically related within the untested and tested cohorts. The untested cohort included a significantly bigger proportion of intermediate-threat sufferers. The primary study consequence was biopsy up-grading, outlined as a rise within the Gleason score from three + three to three + 4 or greater, which was analyzed by Cox proportional hazards regression. In addition, biopsy and prostatectomy specimens have been evaluated domestically without central evaluate. The editorialists additionally observed that once problem to tests such as Oncotype Dx Prostate that report on a continuum of threat is the lack of a transparent, singular threshold that may rule in or rule out the projected consequence. The editorialist suggested that future studies report threshold values with very excessive specificity and sensitivity observed within the study population. The proprietary combination of antibodies used to capture circulating tumor cells is a possible limitation. Whether different methods of isolating prostate-most cancers cells would yield related results should be decided. Their prespecified statistical plan required a sample dimension of 36 taxane-treated men. These molecular alterations might point out the emergence of therapy resistance and could also be targeted for the event of novel agents for prostate most cancers. In the final eight years, many androgen receptor splice variants have been identified and characterised. Increasing evidences highlighted the concept that variant expression could be used as a possible predictive biomarker and a therapeutic target in superior prostate most cancers. Moreover, they acknowledged that continued examination of this biomarker in prospective studies will further aid scientific utility. These investigators acknowledged that prospective trials to validate these findings and further elucidate scientific utility are currently in growth. An accompanying editorial (Montgomery and Plymate, 2016) famous that the assay used in this study could also be much less delicate and 201/512 Tumor Markers Medical Clinical Policy Bulletins | Aetna specific than the assay used within the previously described studies by Antonorakis, et al. Relationships with survival have been analyzed using multivariable Cox regression and log-rank analyses. In addition, it is going to be necessary to establish the biological rationalization for these findings. The authors searched within the Medline and Cochrane Library database from the literature of the previous 10 years. Prostavysion ProstaVysion (Bostwick Labs) is a prognostic genetic panel for prostate most cancers (Raman, et al. By analyzing these two markers, ProstaVysion is ready to provide a molecular evaluation of prostate most cancers aggressiveness and lengthy-time period patient prognosis. Each subtype responds differently to commonplace therapies, and figuring out the subtype permits doctors to tailor therapy for each patient. Assay efficiency traits of the commercially out there model of the test point out excessive reproducibility. The briefing additionally famous that the populations included within the patient cohorts included in these scientific validation studies. Recurrence dangers at three years have been 12 %, 18 %, and 22 % for predefined low, intermediate, and excessive recurrence threat teams, respectively. The assay was carried out on formalin-mounted, paraffinembedded primary most cancers tissue. Studies of the Decipher genetic test have evaluated its correlation with tumor traits (Den, et al. The impact of Decipher was evaluated in a scientific utility study the place 21 uro-oncologists have been offered 24 patient instances (12 potential candidates for adjuvant and 12 for salvage exterior beam radiation remedy) and have been asked for therapy recommendations with and without information from the genetic test (Badani, et al. The recommendation modified in 43% of the adjuvant instances and fifty three% within the salvage setting, suggesting a potentially important impact on therapy decisions after radical prostatectoy. In that study, 43% of sufferers shifted to observation based mostly on information of Decipher genomic classifier after radical prostatectomy. Second, these researchers have been unable to assess the patient�s influence on the therapy determination-making course of. It should be famous, nonetheless, that participants have been community-based mostly physicians quite than these with appointments at tutorial/research centers, and therapy methods might deviate from commonplace apply. Consensus is rising that lengthy-time period, prospective studies in numerous settings will optimize generalizable knowledge to inform finest practices for such technologies. This approach and different recommendations for proof growth was lately beneficial by a diverse and impartial group of researchers, insurers, and policy-makers addressing the challenges of translating the promise of tumor biology research into apply. Using scientific 212/512 Tumor Markers Medical Clinical Policy Bulletins | Aetna information alone, observation was beneficial in forty two% of choices made by urologists versus 23% by radiation oncologists (P <. Each urologist was asked to provide therapy recommendations on 10 instances randomly drawn from a pool of one hundred case histories.
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