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PURPOSE:The Cannabis Consultation Service (CCS) is an innovative pharmacist-led resource at the Sunnybrook Odette Cancer Centre. Its mandate is to provide education and guide patients through access and appropriate use of high-quality plant-derived cannabinoids (PDCs). Our objective was to describe the CCS, explain its processes, and characterize patient disposition with respect to use of PDCs.METHODS:We retrospectively reviewed the charts of patients referred to the CCS from July 13, 2020, to March 05, 2021. We used descriptive statistics to report on the patient population and service metrics.RESULTS:During the 34-week period, 96 patients accessed the CCS (median age, 61 years). The top reasons for CCS consultation were management of cancer pain, insomnia, and general interest. Medical cannabis was supported as an option in 44/96 patients. Reasons for not supporting PDC use included lack of indication, potential drug interaction/contraindication, or requiring treatment with first-line therapy. Of the 40 patients requiring a medical document, 22 initiated therapy. The most common product used was a 2:50 THC:CBD (Tetrahydrocannabinol:Cannabidiol) cannabis oil. At the date of last contact, few patients remained on therapy because of lack of benefit, patient choice, and/or hesitancy.CONCLUSION:Despite patients with cancer having interest in seeking PDCs for symptom management, only a few initiated and continued therapy. Pharmacists have an opportunity to advise patients and the oncology team on the risks and benefits of PDCs. These results can be used to support the development of medical cannabis programs by oncology centers and focus future research priorities.

The recent literature on intrahepatic cholestasis of pregnancy raises questions on the best management of such a disease. Improved evidence might be achieved by meta-analyses.Providing data for allowing individual patients meta-analyses and aggregate data meta-analyses.Data were collected retrospectively at the Fabia Mater Hospital of Rome (Italy), between 2013 and 2018. Several variables were collected and analyzed according to low-level bile acid (less than 40 μmol/L) and high-level bile acid (at least 40 μmol/L). Eighty-three cases of pregnancy cholestasis, diagnosed according to itching symptoms and excluding bile diseases, were collected and analyzed, both descriptively and inferentially.The analyzed data do not provide significant evidence supporting the use of ursodeoxycholic acid to prevent composite adverse fetal outcomes but they can be included in further meta-analyses.

Objective: Episiotomy is associated with an increased risk of postpartum pain, bleeding, and dyspareunia. The hypothesis of this trial was that in women with singleton pregnancy, and spontaneous labor at term, use of calendula ointment would reduce pain after episiotomy. Methods: This was a single-center parallel group randomized trial of women with singleton pregnancies and spontaneous labor at term who were randomized to either use of calendula ointment (i.e. intervention group) or standard care (i.e. control group) after episiotomy. Eligible women were those with singleton gestations in spontaneous labor and vertex presentation at term. Women with premature rupture of membranes were excluded from the study. Women in the intervention group were recommended use of calendula ointment 4 h after the episiotomy and then every 8 h for 10 days. The primary outcome was the pain level. Pain level was self-reported and recorded using the verbal rating scale (VRS). The effect of the calendula ointment was quantified as mean difference (MD) with 95% confidence interval (CI). Results: During the study, 100 women agreed to take part in the study, underwent randomization, and were enrolled in this trial. Of the 100 randomized women, 50 were randomized to the calendula ointment group, and 50 to the control group. No women were excluded after randomization or lost to follow up.Women who received calendula ointment after episiotomy compared to standard care had a significantly lower pain level starting from day two and during all the follow-up. Calendula ointment also improve wound healing in terms of redness and edema. Conclusions: Use of calendula ointment significantly reduce pain after episiotomy.

Objective: To compare maternal blood loss with immediate cord clamping versus delayed cord clamping in women undergoing spontaneous vaginal delivery at term. Methods: Parallel group non-blinded randomized trial conducted at a single center in Italy. Women with singleton gestations who underwent spontaneous vaginal delivery at term were eligible and were randomized in a 1:1 ratio to either immediate or delayed cord clamping. In the immediate cord clamping group, cord clamping was within 15 s after birth. In the delayed cord clamping group, cord clamping was after more than 60 s, or when the cord had stopped pulsing. The primary outcome was change in maternal hemoglobin level from the day of delivery to day one after delivery. Results: A total of 122 participants were enrolled in the trial. There were no significant differences in maternal blood loss as assessed by comparing the decrease in maternal hemoglobin level (mean difference − 0.10 g/dl, 95% confidence interval − 0.28 to 0.08) between the two groups. The mean hemoglobin level at postdelivery day 1 was 11.0 ± 1.5 g/dl in the delayed group and 11.3 ± 1.6 g/dl in the immediate group. Conclusions: Delayed umbilical cord clamping, compared with immediate umbilical cord clamping, resulted in no significant change in maternal hemoglobin level 1 day after delivery. Trial Registration: Clinicaltrials.gov NCT04353544.

During the last decades, the number of couples with reproductive issues has substantially increased. Many different factors are implicated in reproductive failure, including uterine factors. Endometrial pathologies, such as endometrial polyps, hyperplasia, endometritis, and Mullerian anomalies, can also hinder embryo implantation. Hysteroscopy remains the gold standard for the evaluation and treatment of intrauterine pathology. Over the last few years, advances in hysteroscopic instrumentations and surgical techniques have significantly evolved, the refinement in technology, miniaturization of instruments, and improved image quality have rendered hysteroscopy a more patient and user-friendly procedure that has enhanced its use in reproductive medicine. Nowadays, hysteroscopy is essential in the evaluation and treatment of women with infertility. This article underscores the major technological breakthroughs achieved over the last few years with emphasis on the role of artificial intelligence, augmented reality, and 3D hysteroscopy, which can set new benchmarks in hysteroscopy applied to reproductive medicine.

Objective To describe clinical and demographic characteristics, ultrasound appearance, and hysteroscopic outcomes of patients with endometrial osseous metaplasia. Study design We conducted a multicenter retrospective study. We retrospectively reviewed the medical records of all consecutive patients who were referred for hysteroscopy at fourteen institutions in Venezuela, Spain, Morocco, India, Ukraine, Argentina, the United States, and Italy between 1994 and 2018. We identified and included all patients who had a diagnosis of osseous metaplasia at the pathologic report, and data were retrieved from the medical records. Results Between January 1st, 1994, and December 31st, 2018, 63 patients out of a total of 419,673 women who underwent hysteroscopy had a diagnosis of osseous metaplasia (0.015%). Most patients were 31–40 years old (53.7%), were Caucasian or Hispanic (95.5%), and had at least one previous pregnancy (86.9%). Forty-one out of 63 patients (65.1%) had at least one miscarriage before the index hysteroscopy. Dysmenorrhea, abnormal uterine bleeding, and infertility were reported by 34.9%, 27.0%, and 23.8% of patients. 14.3% of women were asymptomatic. Preoperative transvaginal ultrasound was available and identified a hyperechoic area of variable size with posterior acoustic shadowing in all cases. Hysteroscopy was successful without complications in all 63 cases. Follow-up data were available in 30.2% of patients: 69.2% of patients were infertile, and 44.4% of them conceived and achieved a live birth; all other symptoms improved after hysteroscopic treatment in all patients. Conclusions Osseous metaplasia appears associated with multiple unspecific gynecologic symptoms without the predominant role of infertility, as previously suggested. Although endometrial osseous metaplasia is rare, gynecologists should consider this pathologic condition when the characteristic ultrasound appearance is detected, being hysteroscopic treatment effective.

Aim: Assessing awareness of Italian low-risk pregnant patients on low-risk pregnancy care and what do they feel about their own pregnancy. Methods: A questionnaire was administered to 382 low-risk pregnant women. This questionnaire assessed general knowledge of low-risk pregnancy, low-risk pregnancy care, and how much patients rated ten topics of low-risk pregnancy care. It would be expected that the knowledge of each topic would associates with the patient’s perceived importance of that topic. Results: Poor knowledge of pregnancy care was proven. Patients seem to incorrectly overrate vaginal examinations and obstetric and gynecologist-led care, while they attribute appropriate importance to midwife-led care. The more examinations performed (vaginal examinations, sonographic checks, cardiotocographies), the higher their rating. Conclusions: In Italy, expectations of pregnant women about their own pregnancy are incorrectly trusted in the obstetrics and gynecologists. Both poor knowledge of pregnancy care and cultural perspectives on the birth process amongst Italian people explain the finding. Referring low-risk pregnant women to midwives would help them to rate more the care than the caregiver. (www.actabiomedica.it)

Objective: Immersion in water during labor and delivery has been studied as an alternative form of obstetric care. The aim of this study was to evaluate obstetrics and neonatal outcomes of women intending to use immersion in water for labor and delivery. Methods: This was a retrospective observational study conducted at a single center in Italy from January 2004 to January 2016. The clinical records of pregnant women intending to use immersion in water for labor and delivery were collected in a dedicated database and included in the study. Only the women who underwent immersion in water starting from the first stage of labor were included in the study. Inclusion criteria were women with uncomplicated singleton gestations and cephalic presentation at or later than 37 weeks of gestation, and with spontaneous onset of labor. The primary outcome of the study was the percentage of women who had both labor and delivery in water. Results: 389 women met the inclusion criteria and were included in the study. 256 (66%) were nulliparous, and 133 (34%) were multiparous. Out of the 389 women intending to use immersion in water for labor and delivery, 278 (71.5%) had labor and delivery in the water, 31 (8.0%) labor in water and delivery on land, and 80 (20.5%) had the first stage of labor in water, and the second stage and delivery on land. The incidence of perineal lacerations was 61.4%. Conclusion: The vast majority of the women who set out to labor and delivery in water achieve their aim.

Introduction Microglandular adenosis (MGA) is a rare benign proliferative lesion lacking a myoepithelial cell layer; 27% of all reported cases have progressed to invasive carcinoma. Salivary gland-type carcinomas of the breast are also uncommon, representing 2% of all breast cancers. This wide spectrum of neoplasms tends to be triple negative and generally has an excellent prognosis. Given the rarity of salivary gland-type carcinomas of the breast arising from MGA, there are few reports of these cases in literature. As such, there is uncertainty regarding their diagnosis and treatment strategies. Presentation of case We report the rare case of a 66-year-old woman who presented with a triple negative, invasive carcinoma with salivary gland-type features, arising from MGA. The patient underwent mastectomy with sentinel lymph node biopsy, followed by Taxotere and Cyclophosphamide (TC) chemotherapy and 50 Gy in 25 fractions of radiation to her chest wall. We reviewed the available literature on salivary gland-type breast carcinomas arising from MGA. Discussion Despite the generally unfavourable characteristics associated with carcinoma arising in microglandular adenosis (MGACA), most patients with MGACA have favourable outcomes. Conclusions The findings of the present case and reviewed cases are consistent with the literature on MGA, atypical MGA (AMGA), and MGACA. Future study of this rare entity is warranted to establish a consensus surrounding its clinical significance and treatment methods.

Background and purpose: Antiemetic guidelines suggest daily prophylaxis with a serotonin3 receptor antagonist (5-HT3RA) as an option for patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal cancer, despite the risks that 5-HT3RA-induced constipation may pose. We explored the incidence of patient-reported vomiting, retching, nausea and antiemetic intake among patients in this setting to determine if these risks are justified. Materials and methods: We carried out a single-centre non-randomised prospective cohort study of adult patients receiving long-course neoadjuvant radiation therapy and concurrent 5-fluorouracil-based chemotherapy for rectal adenocarcinoma. Patients recorded symptoms and medication intake daily until 7 days following treatment completion. Results: From 33 evaluable patients, we collected 1407 days of patient-reported data. Vomiting was reported by 7 patients (21%), retching by 5(15%) and nausea by 21(64%). No patients were administered prophylactic antiemetics. The median number of days with vomiting was 2, and the cumulative number of days for all affected patients was 22 (1.6% of 1407 evaluable days). There were no differences in PTV or small bowel loop V15Gy, V45Gy and V50Gy volumes between patients that did and did not vomit. Conclusions: The cumulative incidence of days with vomiting was only 1.6%. 5-HT3RA prophylaxis during long-course neoadjuvant treatment seems unnecessary. Keywords: Antiemetic, Nausea, Patient-reported outcome, Radiation therapy, Rectal cancer, Vomiting

Clinical trials in radiation therapy-induced nausea and vomiting (RINV) appear to have varied methodologies, endpoints, and outcome measures. This complicates trial comparisons, weakens practice guideline recommendations, and contributes to variability in supportive care patterns of practice. We systematically reviewed RINV trials to describe and compare their pertinent design features. Ovid versions of the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, EMBASE, and MEDLINE to January/February 2017 were searched for adult phase III trials of RINV management strategies. Key abstracted data included trial interventions and eligibility criteria, standard radiation therapy (RT) metrics, symptom assessment procedures, symptom definitions and grading systems, pre-specified and reported endpoints, and other outcome measures. From 1166 references identified in the initial database search, we selected 34 trials for analysis that collectively randomized 4529 patients (median 61, range 11–1492). Twenty-eight trials (82%) were published prior to the year 2000. Twenty-seven trials (79%) involved multiple fraction RT and 7 (21%) single fraction RT. Twenty-four trials (71%) evaluated prophylactic interventions, 9 (26%) rescue interventions, and 1 trial did not specify. Thirty-three trials (97%) evaluated pharmacologic interventions. Twenty trials (59%) had patient report symptoms, 5 (15%) healthcare professionals or researchers, and 10 (29%) did not specify. Nausea was not defined in any trial but was reported as a stand-alone symptom in 26 trials (76%) and was graded in 20 (59%), with categorical qualitative scales being the most common method. Vomiting was defined in 3 trials (9%), was reported as a stand-alone symptom in 17 (47%), and was graded in 7 (21%), with continuous numerical scales being the most common method. Retching was defined in 3 trials, was not reported as a stand-alone symptom in any trial, and was graded in 1 (3%). Twenty-one trials (62%) created compound symptom measures that combined individual symptoms. Fifteen trials (44%) reported “emetic episode/event” measures but only 9 defined them. Seventeen trials (50%) reported complicated endpoints (e.g., “response,” “control,” “success”) that combined multiple symptom or compound symptom measures, but 7 did not define them comprehensively. Ten trials (29%) defined a primary endpoint a priori. Methodologies, endpoints, and outcome measures varied considerably among 34 randomized trials in RINV.

Inadequate uterine receptivity is responsible for two-third of implanting failures. Aim of the study was to investigate the role of epithelial adherence and tight-junction molecules expressed by human endometrium in predicting womens' fertility outcome. A total of 76 consecutive women, including 24 fertile (G1), 40 primary infertile (G2), and 12 recurrent pregnancy loss (RPL, G3) women, who underwent diagnostic hysteroscopy plus endometrial biopsy between 2005 and 2016 at the Gynecology Division of Sant'Andrea Hospital, Sapienza University of Rome, in Italy, were retrospectively identified and included into the study. Endometrial biopsies were assessed for the immunohistochemical expression of beta-catenin (β-catenin), E-cadherin and K-cadherin biomarkers. Expression profiles were compared between the three groups of patients and were correlated with patients' fertility outcome. In infertile patients there was a significant lower endometrial expression of β-catenin (

STUDY OBJECTIVE To compare the effectiveness and safety of different techniques of hysteroscopic polypectomy. DESIGN Multicenter, prospective observational trial (Canadian Task Force classification II-2). SETTING Nineteen Italian gynecologic departments (university-affiliated or public hospitals). PATIENTS Consecutive patients suffering from endometrial polyps (EPs). INTERVENTIONS Hysteroscopic polypectomy, as performed through different techniques. MEASUREMENTS AND MAIN RESULTS Included in the study were 1404 patients (with 1825 EPs). The setting was an ambulatory care unit in 40.38% of the cases (567 women), of whom 97.7% (554) did not require analgesia/anesthesia. In the remaining 59.62% of women (837 women), the procedures were performed in an operating room under mild sedation, local or general anesthesia. Minor complications occurred in 32 patients (2.27%), without significant differences between the techniques used (p = ns). Uterine perforation occurred in 14 cases, all performed in the operating room with some kind of anesthesia, only 1 with a vaginoscopic technique and the remaining during blind dilatation (odds ratio [OR], 19.98; 95% confidence interval [CI], 1.19-335.79; p = .04). An incomplete removal of EPs was documented in 39 patients. Logistic regression analysis showed that a higher risk of residual EPs was associated with the use of a fiber-based 3.5-mm hysteroscope (OR, 6.78; 95% CI, 2.97-15.52; p

Study Objectives To describe and demonstrate a technique for laparoscopic removal of a perforating intrauterine device (IUD) during pregnancy, and to provide tips to facilitate safe laparoscopic surgery during pregnancy. Design Video presentation of the technique for laparoscopic removal of a perforating IUD in a pregnant woman. Setting Department of Neuroscience, Reproductive Sciences, and Dentistry, University of Naples Federico II, Naples, Italy. Intervention A 30-year-old woman, gravida 3, para 2, with a copper T IUD (Nova T 380; Bayer, Leverkusen, Germany) perforating the left adnexa presented to the emergency room complaining of left lower quadrant pain. The patient had the IUD inserted by her gynecologist 3 months before the onset of the symptoms. Ultrasound revealed a 6-week intrauterine pregnancy with the presence of fetal cardiac activity along with the IUD perforating the left adnexa. The patient returned at 11 weeks of gestation complaining of worsening abdominal pain and excruciating left lower quadrant pain. She was scheduled for laparoscopic excision of the perforating IUD 1 , 2 , 3 . Considering her pregnancy, laparoscopy under regional anesthesia was performed in the minimal Trendelenburg position at 12 degrees, through open laparoscopic access [4] . Intra-abdominal pressure of 8 mmHg and ultrasound energy to cut and coagulate, avoiding monopolar/bipolar energy owing to the presence of a copper IUD, were used. The IUD and tube were extracted in an endobag through umbilical access, under a 5-mm, 0-degree telescope in left lateral access [5] . The procedure was carried out uneventfully, and the IUD was removed. Fetal viability was confirmed after the procedure. At the time of this report, the patient was in the 23rd week of gestation, and the pregnancy was progressing without any problems. Conclusion Laparoscopic removal of perforated IUD during pregnancy under regional anesthesia is a feasible and safe option that should be considered when needed.

Taxane acute pain syndrome (TAPS) is a clinically significant side-effect of taxane chemotherapy, often described as arthralgia and myalgia that occurs 2–3 days after infusion. The aim of this study was to assess pain descriptors used by patients during their experience of TAPS. A clinical prospective cohort study was conducted on breast cancer patients who had not received prior chemotherapy and were asked to complete diaries on three consecutive docetaxel treatment cycles on days 1–7, 14, and 21 (acute phase). Questionnaires to assess pain severity, descriptors of pain, and the interference in activities due to pain were adapted from the Brief Pain Inventory and the McGill Pain Questionnaire. Telephone questionnaire follow-up was done at 1, 3, 6, 9, and 12 months following docetaxel (delayed phase). The most commonly used descriptor for acute and chronic pain was “aching” (90–96%). However, in the delayed phase of the study, “burning” (32–50%), “radiating” (39–48%), and “sharp” (40–69%) were used more often. In both acute and chronic pain phases, most patients experienced moderate/severe pain regardless of the location. Pain in cycle 1 was predictive of pain in subsequent taxane cycles (p

Psoriasis is one of the most common chronic autoinflammatory skin disease, associated with hyperproliferation and abnormal differentiation of keratinocytes, inflammation, and angiogenesis. The available treatments for psoriasis are not curative and may have numerous side effects, and topical administration is preferred over systemic therapy due to the reduced systemic burden of the drug. Thus, novel and more efficacious formulations of anti-inflammatory and/or differentiating compounds for topical application could be very useful for the disease management and for improving the quality of life of the patients. Here we evaluated the potential as anti-psoriatic of an equimolar mixture of two compounds, 2,4-Monofurfurylidene-tetra-O-methylsorbitol (Compound A) and 4,6-dimethyl-2-(3,4,5-trimethoxyphenylamino)pyrimidine (Compound B), that, used individually, are known to possess immunomodulating properties (Compound A) and keratolitic and anti-inflammatory activity (Compound B). Human immortalized keratinocyte cell line (HaCaT cells) and primary human keratinocyte cells from adult donor (HEKa) were used as in vitro experimental models. We show that the mix A + B exhibits antiproliferative activity and induces terminal differentiation more efficiently than compounds A and B used individually. We confirm that the compound B is the active ingredient of the mixture and the mainly responsible for anti-psoriatic activity, but the mix A + B is more effective and possesses lower cytotoxicity than the compound B alone. This could be ascribable to the association with compound A, that is known to possess, in addition to the immunomodulating ability, antioxidant and antiradical action. Our results indicate that mix A + B could be a suitable candidate for a new cosmeceutical formulation for topical treatment of psoriasis.

Results In the base-case analysis, costs associated with no primary prophylaxis, primary prophylaxis with 10 days of filgrastim, and primary prophylaxis with pegfilgrastim were CaD $7 314, CaD $13 947, and CaD $16 290, respectively. The QALYs associated with the three strategies were 0.2004, 0.2015, and 0.2024, respectively. The ICER for the filgrastim vs no primary prophylaxis strategy was CaD $5 796 000 per QALY. The ICER for the pegfilgrastim vs filgrastim primary prophylaxis strategy was CaD $2 611 000 per QALY. All one-way sensitivity analyses yielded ICERs greater than CaD $400 000 per QALY. Cost-effectiveness acceptability curves show that 20.0% of iterations are cost-effective at a willingness-to-pay threshold of CaD $1 595 000 for the filgrastim strategy and CaD $561 000 for the pegfilgrastim strategy.

STUDY QUESTION What classification system is more suitable for the accurate, clear, simple and related to the clinical management categorization of female genital anomalies? SUMMARY ANSWER The new ESHRE/ESGE classification system of female genital anomalies is presented. WHAT IS KNOWN ALREADY Congenital malformations of the female genital tract are common miscellaneous deviations from normal anatomy with health and reproductive consequences. Until now, three systems have been proposed for their categorization but all of them are associated with serious limitations. STUDY DESIGN, SIZE AND DURATION The European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE) have established a common Working Group, under the name CONUTA (CONgenital UTerine Anomalies), with the goal of developing a new updated classification system. A scientific committee (SC) has been appointed to run the project, looking also for consensus within the scientists working in the field. PARTICIPANTS/MATERIALS, SETTING, METHODS The new system is designed and developed based on (i) scientific research through critical review of current proposals and preparation of an initial proposal for discussion between the experts, (ii) consensus measurement among the experts through the use of the DELPHI procedure and (iii) consensus development by the SC, taking into account the results of the DELPHI procedure and the comments of the experts. Almost 90 participants took part in the process of development of the ESHRE/ESGE classification system, contributing with their structured answers and comments. MAIN RESULTS AND THE ROLE OF CHANCE The ESHRE/ESGE classification system is based on anatomy. Anomalies are classified into the following main classes, expressing uterine anatomical deviations deriving from the same embryological origin: U0, normal uterus; U1, dysmorphic uterus; U2, septate uterus; U3, bicorporeal uterus; U4, hemi-uterus; U5, aplastic uterus; U6, for still unclassified cases. Main classes have been divided into sub-classes expressing anatomical varieties with clinical significance. Cervical and vaginal anomalies are classified independently into sub-classes having clinical significance. LIMITATIONS, REASONS FOR CAUTION The ESHRE/ESGE classification of female genital anomalies seems to fulfill the expectations and the needs of the experts in the field, but its clinical value needs to be proved in everyday practice. WIDER IMPLICATIONS OF THE FINDINGS The ESHRE/ESGE classification system of female genital anomalies could be used as a starting point for the development of guidelines for their diagnosis and treatment. STUDY FUNDING/COMPETING INTEREST(S) None.

This study explored international radiation oncology trainee decision making in the management of radiotherapy-induced nausea and vomiting (RINV). Radiation oncology trainees who were members of the national radiation oncology associations of the USA, Canada, Netherlands, Australia, New Zealand, France, Spain and Singapore completed a Web-based survey. Respondents estimated the risks of nausea and vomiting associated with six standardised radiotherapy-only clinical case vignettes modelled after international anti-emetic guidelines and then committed to prophylactic, rescue or no therapy as an initial management approach for each case. One hundred and seventy-six trainees from 11 countries responded. Only 28 % were aware of any anti-emetic guideline. In general, risk estimates and management approaches for the high-risk and minimal risk cases varied less and were more in line with guideline standards than were estimates and approaches for the moderate- and low-risk cases. Prophylactic therapy was the most common approach for the high-risk and a moderate-risk case (83 and 71 % of respondents respectively), while rescue therapy was the most common approach for a second moderate-risk case (69 %), two low-risk cases (69 and 76 %) and a minimal risk case (68 %). A serotonin receptor antagonist was the most commonly recommended prophylactic agent. On multivariate analysis, a higher estimated risk of nausea predicted for recommending prophylactic therapy, and a lower estimated risk of nausea predicted for recommending rescue therapy. Radiation oncology trainee risk estimates and recommended management approaches for RINV clinical case vignettes varied and matched guideline standards more often for high-risk and minimal risk cases than for moderate- and low-risk cases. Risk estimates of nausea specifically were strong predictors of management decisions.

STUDY QUESTION: What is the recommended diagnostic work-up of female genital anomalies according to the European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) system? SUMMARY ANSWER: The ESHRE/ESGE consensus for the diagnosis of female genital anomalies is presented. WHAT IS KNOWN ALREADY: Accurate diagnosis of congenital anomalies still remains a clinical challenge because of the drawbacks of the previous classification systems and the non-systematic use of diagnostic methods with varying accuracy, some of them quite inaccurate. Currently, a wide range of non-invasive diagnostic procedures are available enriching the opportunity to accurately detect the anatomical status of the female genital tract, as well as a new objective and comprehensive classification system with well-described classes and sub-classes. STUDY DESIGN, SIZE, DURATION: The ESHRE/ESGE CONgenital UTerine Anomalies (CONUTA) Working Group established an initiative with the goal of developing a consensus for the diagnosis of female genital anomalies. The CONUTA working group and imaging experts in the field have been appointed to run the project. PARTICIPANTS/MATERIALS, SETTING, METHODS: The consensus is developed based on: (i) evaluation of the currently available diagnostic methods and, more specifically, of their characteristics with the use of the experts panel consensus method and of their diagnostic accuracy by performing a systematic review of evidence and (ii) consensus for the definition of where and how to measure uterine wall thickness and the recommendations for the diagnostic work-up of female genital anomalies, based on the results of the previous evaluation procedure, with the use of the experts panel consensus method. MAIN RESULTS AND THE ROLE OF CHANCE: Uterine wall thickness is defined as the distance between the interostial line and external uterine profile at the midcoronal plane of the uterus; alternatively, if a coronal plane is not available, the mean anterior and posterior uterine wall thickness at the longitudinal plane could be used. Gynecological examination and two-dimensional ultrasound (2D US) are recommended for the evaluation of asymptomatic women. Three-dimensional (3D) US is recommended for the diagnosis of female genital anomalies in 'symptomatic' patients belonging to high risk groups for the presence of a female genital anomaly and in any asymptomatic woman suspected to have an anomaly from routine evaluation. Magnetic resonance imaging (MRI) and endoscopic evaluation are recommended for the subgroup of patients with suspected complex anomalies or in diagnostic dilemmas. Adolescents with symptoms suggestive for the presence of a female genital anomaly should be thoroughly evaluated with 2D US, 3D US, MRI and endoscopically. LIMITATIONS, REASONS FOR CAUTION: The various diagnostic methods should always be used in the proper way and evaluated by experts to avoid mis-, over- and underdiagnosis. WIDER IMPLICATIONS OF THE FINDINGS: The role of a combined US examination and outpatient hysteroscopy should be prospectively evaluated. It is a challenge for further research, based on diagnosis, to objectively evaluate the clinical consequences related to various degrees of uterine deformity. STUDY FUNDING/COMPETING INTERESTS: None.

Studies have demonstrated that patients at low risk for febrile neutropenia (FN) complications can be treated safely and effectively at home. Information on patient preferences for outpatient treatment of this condition will help to optimize health care delivery to these patients. The purpose of this study was to elicit non-Hodgkin lymphoma patients' preferences on attributes related to outpatient treatment of FN.We used a self-administered discrete choice experiment questionnaire based on the attributes of out-of-pocket costs, unpaid caregiver time required daily, and probability of return to the hospital. Ten paired scenarios in which levels of the attributes were varied were presented to study patients. For each pair, patients indicated the scenario they preferred. Adjusted odds ratios (ORs) of accepting a scenario that described outpatient care for FN were estimated.Eighty-eight patients completed the questionnaire. Adjusted ORs [95 % confidence intervals] of accepting outpatient care for FN were 0.84 [0.75, 0.95] for each $10 increase in out-of-pocket cost; 0.82 [0.68, 0.99] for each 1 h increase in daily unpaid caregiver time; and 0.53 [0.50, 0.57] for each 5 % increase in probability of return to the hospital.Probability of return to the hospital was the most important attribute to patients when considering home-based care for FN. Patients considered out-of-pocket costs and unpaid caregiver time to be less important than probability of return to the hospital. This study identifies factors that could be incorporated into outpatient delivery systems for FN care to ensure adequate patient uptake and satisfaction with such programs.

Introduction 5-HT3 receptor antagonists (5-HT3RAs) are the most commonly recommended agents for the prophylaxis of radiotherapy-induced nausea and vomiting (RINV) within international antiemetic guidelines. However, the optimal timing and duration of their administration is unknown. We reviewed the relevant literature as a first step in addressing this important issue in supportive care.

Radiotherapy-induced nausea and vomiting (RINV) are common and troublesome symptoms experienced by patients undergoing radiotherapy. Although quality of life and symptom control now figure prominently in evaluations of cancer therapies, progress in RINV research and clinical prevention has been slow. This article summarizes the major guidelines for the prevention of RINV; their structure, recommendations, evidence base and notable issues. It also examines the current challenges and controversies related to RINV clinical management and research, and provides possible solutions for them that could ultimately lead to better patient care.

The mammalian spleen has important functions in immunity and haematopoiesis but little is known about the events that occur during its early embryonic development. Here we analyse the origin of the cells that gives rise to the splenic mesenchyme and the process by which the precursors assume their position along the left lateral side of the stomach. We report a highly conserved regulatory element that regulates the Nkx2-5 gene throughout early spleen development. A transgenic mouse line carrying this element driving a reporter gene was used to show that morphogenesis of the spleen initiates bilaterally and posterior to the stomach, before the splenic precursors grow preferentially leftward. In addition the transgenic line was used in an organ culture system to track spleen precursor cells during development. Spleen cells were shown to move from the posterior mesenchyme and track along the left side of the stomach. Removal of tissue from the anterior stomach resulted in splenic cells randomly scattering suggesting a guidance role for the anterior stomach. Using a mouse line carrying a conditional Cre recombinase to mark early precursor cell populations, the spleen was found to derive from posterior mesenchyme distinct from the closely adjacent stomach mesenchyme.

The mechanism by which left-right (LR) information is interpreted by organ primordia during asymmetric morphogenesis is largely unknown. We show that spleen and pancreatic laterality is dependent on a specialised, columnar mesodermal-derived cell layer referred to here as the splanchnic mesodermal plate (SMP). At early embryonic stages, the SMP is bilateral, surrounding the midline-located stomach and dorsal pancreatic bud. Under control of the LR asymmetry pathway, the left SMP is maintained and grows laterally. Mice carrying the dominant hemimelia (Dh) mutation lack the SMP. Significantly, the mice are asplenic and the pancreas remains positioned along the embryonic midline. In the absence of Fgf10 expression, the spleno-pancreatic mesenchyme and surrounding SMP grow laterally but contain no endodermal component, showing that leftward growth is autonomous and independent of endoderm. In the Bapx1–/–mutants, the SMP is defective. Normally, the SMP is a source for both Fgf9 and Fgf10; however, in the Bapx1 mutant, Fgf10 expression is downregulated and the dorsal pancreas remains at the midline. We conclude that the SMP is an organiser responsible for the leftward growth of the spleno-pancreatic region and that Bapx1 regulates SMP functions required for pancreatic laterality.

Aims: To review the impact of female genital malformations as well as their different types on pregnancy outcome. Methods: Pertinent studies were identified through a computer Medline, Embase and Cochrane Library search. Uterine defects were grouped into five classes, according to the new ESHRE/ESGE Classification of Female Genital Malformations. Only data on untreated congenital uterine anomalies, apart for metroplasty in bicornuate uterus, were taken into account in accordance to the objective of the issue. Clinical implications: Those uterine malformations that cannot be surgically treated (Hemi-uterus and Bicorporeal uterus with double cervix – AFS Unicornuate and Didelphys uteri) are associated with poor reproductive performances, increased abortion rates and lower live birth rates, eventhough a successful pregnancy is possible. On the opposite, septate uterus, hypoplastic uterus (AFS “T-shaped” ) and partial unification defects (AFS bicornuate uterus) are associated to the worst reproductive outcomes when untreated and to the higher reproductive performances after surgery. Open issue: The hypoplastic uterus (T-shaped/Uterus Infantilis) is an old/new congenital pathology to be taken into account, both for its increasing incidence and damage of reproductive outcome and for the promising results of hysteroscopic surgery in those patients.

To estimate, using a time and motion method, the time and labor costs associated with the administration of zoledronic acid and pamidronate in cancer patients with metastatic bone diseases.During clinic visits for participating patients receiving intravenous zoledronic acid or pamidronate, all times and activities associated with the administration of bisphosphonates were recorded by a trained observer using a stopwatch and data recording forms. The total time associated with the administration of bisphosphonates was estimated and converted to labor costs by applying corresponding health care professional hourly wage rates plus the fringe-benefit rate. The costs were presented in 2011 Canadian dollars.A convenience sample of 37 patients from 2 hospital outpatient oncology clinics in Ontario and Quebec participated in the study. Nineteen patients were diagnosed with breast cancer and 18 with prostate cancer. The average patient age was 66 years, and patients had been diagnosed with cancer and metastatic bone disease for 8 years and 3 years, respectively. The times and costs associated with the administration of bisphosphonates for the 28 patients who did not receive concurrent chemotherapy during the scheduled clinic visits are also reported. The mean infusion time for patients receiving zoledronic acid was 20.6 minutes. With the use of ambulatory infusion devices, the mean infusion time of pamidronate was 23 minutes (limited to observations of patients who were seated during administration). In contrast, the mean infusion time using regular infusion devices was 162 minutes. The mean labor cost for administering zoledronic acid was $20. The mean labor cost for administering pamidronate was $10 using ambulatory infusion devices and $68 using regular infusion devices.The time burden to cancer patients with metastatic bone disease who receive intravenous bisphosphonates and the costs to the health care system are substantial, especially when regular infusion devices are used.

Study Objective To describe the hysteroscopic findings in patients complaining of menorrhagia to establish any significant association between menorrhagia and benign/malignant intrauterine disorders. Design Prospective cohort study (Canadian Task Force classification II). Setting University La Sapienza, Rome, Italy. Patients One hundred eighteen premenopausal women undergoing office hysteroscopy for menorrhagia (group A) and 344 premenopausal patients undergoing office hysteroscopy for other indications (noncyclic abnormal uterine bleeding, infertility, ultrasonographic abnormalities, etc) (group B). Interventions Office hysteroscopy. Measurement and Main Results Data on the prevalence of hysteroscopic findings (cervical polyps, endometrial polyps, submucous myomas, low-grade hyperplasia and high-grade hyperplasia/endometrial carcinoma) were compared between group A and group B. The total prevalence, as well as the prevalence of type 0 and type I myomas (totally or >50% intracavitary, respectively), and the mean number per patients with submucous myomas was significantly higher in group A compared with group B (p = .0001, p = .024, and p = .017, respectively). Multivariable logistic regression analysis showed a statistically significant association between age (odds ratio 4.15, 95% confidence interval 1.55–11.1 in the 40- to 49-year age group), presence of submucous myomas (odds ratio 2.76, 95% confidence interval 1.52–5.00), and menorrhagia. Conclusions Menorrhagia seems to be associated with aging, the presence and number of submucous myomas, and with the degree of their intracavitary development.

To describe 3 cases of misplaced or retained Intrauterine Contraceptive (IUC) that were successfully resolved by hysteroscopy performed in an ambulatory setting using miniaturized electrosurgical and mechanical operative instruments.Step-by-step description of the technique using slides, pictures, and video (educative video) (Canadian Task Force classification III).Misplaced or retained IUC may be related to several causes; incorrect insertion is the leading cause. In these cases, patients may complain of abnormal bleeding, pelvic pain, or pregnancy or they may remain asymptomatic. When a displaced IUC is suspected, transvaginal ultrasonography is the primary investigation followed by radiography in cases in which the IUC is not seen within the uterus. Additional imaging such as computed tomographic scanning or magnetic resonance imaging may be needed. Hysteroscopy represents the gold standard for diagnostic clarification and management of a dislocated or embedded IUC.The hysteroscopic approach of the 3 cases was the following: removal of a partially perforating IUD in the cesarean scar pouch, repositioning of a dislocated IUS in the isthmocele, and removal of an embedded IUS in the cornual area. The procedures were performed in an ambulatory setting using a 5-mm continuous flow hysteroscope and vaginoscopic approach without any analgesia and/or anesthesia. The alternate use of mechanical and electrosurgical 5F instruments allowed us to separate the IUC from the myometrial uterine wall, respecting the healthy myometrium and without causing significant patient discomfort or complications.The possibility of using miniaturized electrosurgical and mechanical instruments with small-diameter hysteroscopes offers the possibility of an effective, safe, cost-efficient, and well-tolerated removal or repositioning of a misplaced or retained IUC. This minimally invasive approach can be performed in an office setting to avoid more invasive and traumatic approaches.

Purpose To investigate international patterns of practice in the management of radiation therapy-induced nausea and vomiting (RINV). Methods and Materials Oncologists prescribing radiation therapy in the United States, Canada, The Netherlands, Australia, New Zealand, Spain, Italy, France, Hong Kong, Singapore, Cyprus, and Israel completed a Web-based survey that was based on 6 radiation therapy-only clinical cases modeled after the minimal-, low-, moderate-, and high-emetic risk levels defined in the antiemetic guidelines of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer. For each case, respondents estimated the risks of nausea and vomiting separately and committed to an initial management approach. Results In total, 1022 responses were received. Risk estimates and management decisions for the minimal- and high-risk cases varied little and were in line with guideline standards, whereas those for the low- and moderate-risk cases varied greatly. The most common initial management strategies were as follows: rescue therapy for a minimal-risk case (63% of respondents), 2 low-risk cases (56% and 80%), and 1 moderate-risk case (66%); and prophylactic therapy for a second moderate-risk case (75%) and a high-risk case (95%). The serotonin (5-HT) 3 receptor antagonists were the most commonly recommended prophylactic agents. On multivariate analysis, factors predictive of a decision for prophylactic or rescue therapy were risk estimates of nausea and vomiting, awareness of the American Society of Clinical Oncology antiemetic guideline, and European Society for Therapeutic Radiology and Oncology membership. Conclusions Risk estimates and management strategies for RINV varied, especially for low- and moderate-risk radiation therapy cases. Radiation therapy-induced nausea and vomiting are under-studied treatment sequelae. New observational and translational studies are needed to allow for individual patient risk assessment and to refine antiemetic guideline management recommendations.

BACKGROUND: At Sunnybrook Health Sciences Centre in Toronto, Ontario, the recommended empiric regimen for febrile neutropenia has been cefazolin and tobramycin for at least 25 years. However, we had no objective data to reassure us that patient mortality had not increased over the past five years.METHODS: A retrospective chart review of 48 episodes occurring in 44 patients admitted for the treatment of febrile neutropenia secondary to chemotherapy in 2002, and initially managed with cefazolin and tobramycin was conducted. Prospective data from 48 episodes in 2007 had previously been collected. Patients who developed febrile neutropenia while in hospital were excluded. The primary objective of the present study was to compare the all-cause mortality in 2007 with that from 2002.RESULTS: There were no statistically significant differences between the groups (P>0.05). All-cause mortality in 2007 was 8.3% (four of 48) compared with 10.4% (five of 48) in 2002 (P=1). All deaths occurred in patients considered to be at high risk according to the Talcott score.CONCLUSION: Mortality has not increased in the past five years with the use of empiric cefazolin and tobramycin for the treatment of patients admitted with febrile neutropenia at Sunnybrook Health Sciences Centre. Rates are comparable with those reported in the literature for similar patients. The results of the present study provide reassurance that the regimen continues to be effective for lower-risk febrile neutropenic patients.

Constipation is a highly prevalent and distressing symptom in patients with advanced, progressive illnesses. Although opioids are one of the most common causes of constipation in patients with advanced, progressive illness, it is important to note that there are many other potential etiologies and combinations of causes that should be taken into consideration when making treatment decisions. Management approaches involve a combination of good assessment techniques, preventive regimens, appropriate pharmacological treatment of established constipation, and frequent monitoring. In this vulnerable patient population, maintenance of comfort and respect for individual preferences and sensitivities should be overriding considerations when making clinical decisions. This consensus document was developed by a multidisciplinary group of leading Canadian palliative care specialists in an effort to define best practices in palliative constipation management that will be relevant and useful to health care professionals. Although a wide range of options exists to help treat constipation and prevent its development or recurrence, there is a limited body of evidence evaluating pharmacological interventions. These recommendations are, therefore, based on the best of the available evidence, combined with expert opinion derived from experience in clinical practice. This underscores the need for further clinical evaluation of the available agents to create a robust, evidence-based foundation for treatment decisions in the management of constipation in patients with advanced, progressive illness.

To provide family physicians and pharmacists with practical, evidence- and expertise-based guidance on choosing the safest approach to using analgesics to manage patients with musculoskeletal pain.Health care providers from family practice, rheumatology, gastroenterology, hepatology, internal medicine, and pharmacy participated in an educational needs assessment regarding the management of pain and the safety of commonly used analgesics. Feedback from one-on-one interviews was compiled and distributed to participants who selected key topics. Topics chosen formed the basis for the discussions of this multidisciplinary panel that reviewed data on the safety of analgesics, particularly in regard to comorbidity and concurrent use with other therapies.Treatment should begin with an effective analgesic with the best safety profile at the lowest dose and escalate to higher doses and different analgesics as required. Acetaminophen is a safe medication that should be considered first-line therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with potential adverse gastrointestinal, renal, hepatic, and cardiovascular effects. Physicians should not prescribe NSAIDs before taking a careful history and doing a physical examination so they have the information they need to weigh the risks (adverse effects and potential drug interactions) and benefits for individual patients.Taking a complete and accurate history and doing a physical examination are essential for choosing the safest analgesic for a particular patient.