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Background: Here, the perspective of patients with primary and secondary immunodeficiency receiving subcutaneous immunoglobulin (SCIg) via introductory smaller size pre-filled syringes (PFS) or vials were compared. Methods: An online survey was conducted in Canada by the Association des Patients Immunodéficients du Québec (APIQ) (10/2020–03/2021). Survey questions included: reasons for choosing SCIg packaging and administration methods, training experiences, infusion characteristics, and switching methods. The survey captured structured patient-reported outcomes: treatment satisfaction and its sub-domains, symptom state, general health perception, and physical and mental function. Respondents using PFS were compared with vial users, overall and stratified by their administration method (pump or manual push). Results: Of the 132 total respondents, 66 respondents used vials, with 38 using a pump and 28 using manual push. PFS (5 and 10 mL sizes) were being used by 120 respondents, with 38 using a pump and 82 using manual push. PFS users were associated with a 17% lower median (interquartile range) SCIg dose (10 [8, 12] vs. 12 [9, 16] g/week, respectively), a significantly shorter infusion preparation time (15 [10, 20] vs. 15 [10, 30] mins, respectively), and a trend for shorter length of infusion (60 [35, 90] vs. 70 [48, 90] mins, respectively) compared with those on vials. Patient-reported treatment satisfaction scores were overall similar between vial and PFS users (including on the domains of effectiveness and convenience), except for a higher score for vials over PFS on the domain of global satisfaction (p=0.02). Conclusions: Consistent with prescribing that reflects a recognition of less wastage, PFS users were associated with a significantly lower SCIg dose compared with vial users. PFS users were also associated with shorter pre-infusion times, reflecting simpler administration mechanics compared with vial users. Higher global satisfaction with treatment among vial users compared with PFS users was consistent with users being limited to smaller PFS size options in Canada during the study period. Patient experience on PFS is expected to improve with the introduction of larger PFS sizes. Overall, treatment satisfaction for SCIg remains consistently high with the introduction of PFS packaging compared with vials. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous immunoglobulin (SCIG) is increasingly utilized in primary immunodeficiency (PI). Understanding factors associated with treatment experience and satisfaction can optimize patient outcomes. We analyzed Immune Deficiency Foundation (IDF) survey data to evaluate patient-reported outcomes (PROs) in relation to SCIG training and infusion characteristics. Respondents' PRO scores were rank ordered into 'best', 'intermediate', and 'worst' tertiles. Predicted probabilities of being in the best tertile with any combination of characteristics were generated for each PRO. Results: In 366 SCIG respondents, higher odds of being in the best PRO tertile were driven by favorable training characteristics (particularly, higher confidence post-training and no training barriers) and efficient infusions (infusion preparation ≤20 min and actual infusion < 2 h). Age (≤17 years old) and treatment experience (> 2 years) increased the odds of being in the best tertiles. Compared with the least favorable training/infusion characteristics, those with the most favorable training/infusion characteristics had higher predicted probabilities of being in the best tertiles: TSQM side effects, 59% vs 4%; convenience, 52% vs 4%; effectiveness, 27% vs 13%; global, 26% vs 3%; PROMIS Fatigue, 44% vs 18%. Conclusions: Increased experience with SCIG consistently improved PROs, but our findings predicted that enhanced training and infusion characteristics improve patient treatment satisfaction beyond that achieved by experience alone. [ABSTRACT FROM AUTHOR]

Background and purpose: Chronic inflammatory demyelinating polyneuropathy (CIDP) causes weakness which adversely impacts function and quality of life (QOL). CIDP often requires long‐term management with intravenous or subcutaneous immunoglobulin. The Polyneuropathy and Treatment with Hizentra® (PATH) study showed that subcutaneous immunoglobulin (SCIG) was efficacious in CIDP maintenance. Here, patient‐reported outcomes in patients on SCIG are assessed. Methods: Subjects stabilized on intravenous immunoglobulin were randomly allocated to receive weekly 0.2 or 0.4 g/kg bodyweight of 20% SCIG (IgPro20) or placebo. Overall QOL/health status was assessed using the EuroQoL 5‐Dimension (EQ‐5D) health profile and visual analog scale, treatment satisfaction was assessed with the Treatment Satisfaction Questionnaire for Medicine (TSQM) and work‐related impact was assessed with the Work Productivity and Activity Impairment Questionnaire for General Health (WPAI‐GH). The EQ‐5D health profile was assessed in terms of the percentage of subjects maintained or improved at week 25 of SCIG therapy on each of the EQ‐5D domains versus baseline after intravenous immunoglobulin stabilization. TSQM and WPAI‐GH were assessed by median score changes from baseline to week 25. Results: In total, 172 subjects were randomized to placebo (n = 57), 0.2 g/kg IgPro20 (n = 57) and 0.4 g/kg IgPro20 (n = 58). Significantly higher proportions of IgPro20‐treated subjects improved/maintained their health status on the EQ‐5D usual activities dimension, and in additional dimensions (mobility and pain/discomfort) in sensitivity analyses. TSQM and WPAI‐GH scores were more stable with IgPro20 treatment compared with placebo. Conclusions: IgPro20 maintained or improved QOL in most subjects with CIDP, consistent with the PATH study findings that both IgPro20 doses were efficacious in maintaining CIDP. [ABSTRACT FROM AUTHOR]

Objectives: Our primary objective was to assess patient awareness by observing Google Trends comparing search terms used in relation to morcellation rather than morcellation alone. Our secondary objective was to review trends and locations of publications on leiomyosarcoma and morcellation following the US Food and Drug Administration (FDA) position statement.Study Design: To assess Internet trends, we obtained the relative search volume (RSV) for each month from 1 January 2004 to 1 March 2019 from Google Trends using the terms 'fibroid', 'morcellation', and 'fibroid cancer'. RSV ranges from 0 to 100 with 100 being peak popularity for the term, and all other monthly search activity relative to the peak. To assess academic trends, we performed a systematic review of published literature discussing fibroid morcellation within the same time period. We used a two-way independent t-test to compare median RSV, and chi-squared test to compare academic output. P < 0.05 was considered statistically significant.Results: Search volume for 'morcellation' peaked during the FDA statement (RSV 0.5 to 2.9, t = 17.5, p < 0.05) but was not sustained. There is an increase in 'fibroid' activity post-FDA statement (RSV 68.8 to 76.3, t = 3.9, p < 0.05). 'Fibroid cancer' remained static throughout (t = 1.5, p = 0.1 and t=-0.5, p = 0.6). Afro-Caribbean countries had the highest RSV for 'fibroid', whereas 'morcellation' RSV was highest in predominantly Western countries. There was a significant increase in the rate of papers published on the subject following the FDA statement (6.8 vs 55.6 papers per year, 95% CI -53.96 to -43.64, p < 0.0001). No academic papers on morcellation were published from countries with the highest RSV for 'fibroid'.Conclusion: Our study suggests that interest in uterine fibroids has increased since the FDA statement, but the public are perhaps unaware or not concerned of the consequent potential risk of leiomyosarcoma following morcellation. Countries where fibroid interest is highest are not necessarily those that can offer power morcellation. Further studies are required to address how the Internet influences patient choice and informed consent, and how medical professionals can use it to further educate patients on the risks and benefits of laparoscopic myomectomy and power morcellation. [ABSTRACT FROM AUTHOR]

REFERENCES 1 Zbiri S, Fauconnier A, Milcent C. Care for uterine fibroids: another casualty of the COVID pandemic. We read with interest the recently published article by Saad Zbiri[1] and colleagues "Care for uterine fibroids: another casualty of the COVID pandemic', addressing the poor care of women with fibroids during the COVID-19 pandemic. Finally, access to emergency care may only be the tip of the iceberg with regard to the negative impact on women with fibroids during the pandemic. [Extracted from the article]

A field experiment was conducted during rabi (winter) seasons of 2007-08 and 2008-09 to study the effect of integrated nutrient management on growth, yield, oil content and nutrient uptake of yellow sarson (Brassica campestris L var. yellow sarson) in older alluvial soil of West Bengal. Significantly higher leaf area index (1.75 at 40 days after sowing; DAS), dry matter accumulation (1366.9 g/m2 at 80 DAS) and highest number of siliquae/plant (118.3), number of seeds/siliqua (21.8), seed yield (1.90 t/ha), stover yield (3.86 t/ha) were recorded significantly (at 5% level) higher with poultry manure (PM) @2.5t/ha +50%RDF (Recommended Dose of Fertilizer i.e. 80-40-40 of N-P2O5-K2O kg/ha) + PSB (phosphate solubilising bacteria) + AZ (Azotobacter) during both the years and on pooled basis. An average of 30.5% and 233% increase in seed yield by this treatment was recorded over sole application of RDF and control respectively. Integrated application of PM (2.5 t/ha) + 50% RDF + PSB + AZ recorded highest oil content (43.16%) and positive effect on soil fertility status. The highest benefit: cost ratios (2.26 and 2.4 in 2007-'08 and 2008-'09 respectively) were achieved from the use of 50% RDF + PM (2.5 t/ha) +PSB+AZ. [ABSTRACT FROM AUTHOR]

A field experiment was conducted during rabi season of 2007-'08 and 2008-'09 to study the effect of calcium nitrate {Ca (NO3)2} and potassium nitrate {KNO3} at 50 % flowering stage and soil applied nitrogen {N: (0, 40 and 80 kg N/ha)} on growth, productivity and economics of yellow sarson at farmers field under irrigated old alluvial soil of West Bengal. Highest leaf area index (LAI) values at 40 days of crop age (1.748 and 1.592), dry matter accumulation (1404.3 and 1288.8 gm-2) at 80 days and crop growth rate (C.G.R) (27.87 and 25.68 g m-2 day-1) in between 40 to 60 days were obtained at Nitrogen application at the rate of 80 kg / ha and mixed spray of 0.203 % Ca (NO3)2 + 0.25 % KNO3 respectively. Soil application of 80 kg N/ ha along with foliar spray of 0.203 % Ca (NO3)2 + 0.25 % KNO3 resulted increase in seed yield (1.68 t ha-1) by 12 % over 80 kg N/ ha with only water spray (1.5 t ha-1). Foliar spray of 0.203 % Ca (NO3)2 + 0.25 % KNO3 improved the yield components and seed yield over their sole application. Application of 80 kg N/ha along with 0.203 % Ca (NO3)2 + 0.25 % KNO3 at 50 % flowering stage was found to be the most effective in increasing yellow sarson production in old alluvial soil. [ABSTRACT FROM AUTHOR]

Compact stars such as neutron stars (NS) can have either hadronic or exotic states like strange quark or colour superconducting matter. Stars can also have a quark core surrounded by hadronic matter, known as hybrid stars (HS). The HS is likely to have a mixed phase in between the hadron and the quark phases. Observational results suggest huge surface magnetic field in certain NS. Therefore, we study here the effect of strong magnetic field on the respective equation of states (EOS) of matter under extreme conditions. We further study the hadron-quark phase transition in the interiors of NS giving rise to HS in the presence of strong magnetic field. The hadronic matter EOS is described based on RMF theory and we include the effects of strong magnetic fields leading to Landau quantization of the charged particles. For quark phase, we use the simple Massachusetts Institute of Technology (MIT) bag model, assuming density-dependent bag pressure and magnetic field. The magnetic field strength increases from the surface to the centre of the star. We construct the intermediate mixed phase using Glendenning conjecture. The magnetic field softens the EOS of both the matter phases. We finally study, the mass-radius relationship for such types of mixed HS, calculating their maximum mass, and compare them with the recent observations of pulsar PSR J1614-2230, which is about 2 solarmass. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This retrospective study used the US Oncology iKnowMed™ database, billing claims, and chart reviews to report treatment patterns and outcomes in late-stage non-small cell lung cancer (NSCLC) in US community oncology practices. Materials and methods: Eligibility criteria included non-squamous NSCLC, stage IIIB/IV at diagnosis, ECOG performance status (PS) <3, and initiation of 2nd-line therapy (defined as index date) between 1/1/2007 and 6/30/2011 with ≥1 year follow-up. Key outcomes were overall survival (OS), progression-free survival (PFS), time-to-progression (TTP), and time-to-hospitalization (post-index date). Kaplan–Meier and Cox proportional hazard models were used to characterize the distribution and predictors of outcomes. Results: 1168 patients were eligible for the study. The most frequent 2nd-line therapies were pemetrexed (54.4%), erlotinib-containing regimens (17.6%), and docetaxel (10.0%). Median OS and PFS were 7.5 (95% confidence interval [CI]: 6.6–8.4) and 4.1 (95% CI: 3.7–4.5) months, respectively; 57% of patients were hospitalized post-index date. EGFR testing rates were 2.3% before 2010, 15.2% in 2010, and 32.0% in 2011 (P <.001). Of EGFR-positive patients, 50.0% received erlotinib-containing regimens compared with 16.9% of EGFR-negative patients (P =0.001). An increased risk of shorter time-to-hospitalization, after controlling for other covariates, was associated with PS=1 (hazard ratio [HR]=1.51; P <.001) or PS=2 (HR=1.68; P =.001) compared with PS=0, pre-existing comorbid fatigue (HR=1.64; P =.003) compared with no comorbid fatigue, and progression (HR=1.92; P <.001), when it occurred, compared with no progression. Compared with other 2nd-line treatment, erlotinib-containing regimens prolonged adjusted TTP (HR=0.69; P =.015). Conclusions: This retrospective observational study provides new insights into treatment patterns, biomarker testing, and outcomes in advanced NSCLC within the context of a large community oncology network. Outcomes of these community practice patients, although poor, were similar to those reported in 2nd-line clinical trials for relevant regimens. EGFR testing in community practice rose rapidly after 2010. [Copyright &y& Elsevier]

Intrusion of water through longitudinal joints can cause premature distress in hot mix asphalt (HMA) pavements. Similar to mat permeability, joint permeability is a critical factor governing the performance of HMA pavements. Hence, joint permeability should be used as a measure of quality of joint construction. In this ongoing study, a simple and effective permeameter has been developed, and used in a rational method to evaluate the permeability of longitudinal joints, relative to the permeability of the adjacent mat. The permeameter consists of three standpipes, which can be used for measuring the flow of water through a joint and through the mat on either side of the joint. Results from testing on several projects show that this permeameter can be used successfully to determine permeability of joints. The testing performed in this study shows that joints have significantly higher permeability compared to adjacent mats, different types of joints have different permeabilities and that treatment of joints with sealers and using improved joint construction techniques such as joint heater can reduce the permeability significantly. More testing of joints is being carried out, with the objective of developing specific criteria for using the joint permeameter for quality control of construction of longitudinal joints. [ABSTRACT FROM AUTHOR]

It has previously been demonstrated that hyperthermia can activate prostaglandin synthesis and that prostaglandins are protective against hyperthermia. This study examined the use of inhibitors of prostaglandin synthesis on the response of prostate tumours to hyperthermia. The non-steroidal anti-inflammatory drugs (NSAID) ibuprofen and sulindac, known cyclooxygenase inhibitors that inhibit prostaglandin production, were effective hyperthermia sensitizers and augmented growth delay of DU-145 and PC-3 prostate tumours to combined radiation and hyperthermia treatment protocols. Pre-treatment of mice with ibuprofen and sulindac at hyperthermia sensitizing doses resulted in significant (p < 0.01) inhibition of hyperthemia-induced serum prostaglandin E[sub 2]. These findings indicate that NSAID may have both sensitizing effects on prostate tumour growth and may function by inhibiting prostaglandin synthesis. [ABSTRACT FROM AUTHOR]

Reported findings of elevated risk of adverse events associated with calcium channel blocker use in hypertensives may be due partly to unmeasured confounding by indication. To determine if such confounding occurs, we conducted a retrospective cohort analysis of 77 196 Pennsylvania Medicaid recipients aged 18 to 61 who were treated with antihypertensive medication between 1990 and 1992. All diagnoses and dispensed prescriptions during the year prior to study entry were examined. Prior recipients of multitherapy (n = 18 763) were more likely to have had previously diagnosed risk factors (OR = 1.31 [95% CI, 1.30-1.33]) than subjects with prior monotherapy (n = 11141). New initiators (n = 47292) were less likely to have had previously diagnosed risk factors (OR = 0.48 (95% CI, 0.47-0.49)) than previous users (n = 29904). The likelihood of being prescribed calcium channel blocker rather than other monotherapy was significantly higher for subjects diagnosed during the previous week with arteriosclerotic cardiovascular disease OR = 7.78 (95% CI, 2.72-22.28), P < 0.0001; angina OR = 2.92 (95% CI, 1.77-4.83), (P < 0.0001); diabetes OR = 1.49 (95% CI, 1.07-2.06), (P = 0.0004); and hypertension OR = 1.57 (95% CI 1.35-1.82), (P < 0.0001). Calcium channel blockers were selectively prescribed to subjects at elevated risk of adverse events. Confounding by indication was found in this large indigent population. Unmeasured confounding may contribute to overestimated relative risk of adverse events associated with calcium channel blocker therapy vs diuretics or beta-blockers. At least 1 full year of subjects' medical and prescription drug history should be examined prior to study entry; shorter observation periods will miss clinically relevant information about risk. [ABSTRACT FROM AUTHOR]

Phase transformations in near Ti2AlNb alloy occurring on cooling of 10 °C min−1 from 1020 °C were studied in situ using high energy X-ray diffraction and electrical resistivity measurements coupled with simultaneous dilatometric analysis. From Rietveld refinement of X-ray data, it was established that high temperature range from about 870 to 1020 °C contained partially ordered β phase. The degree of long-range order was of 0.6 at 1020 °C and decreased slowly with temperature decrease and fast when O-phase was formed. The formation of O-Ti 2 AlNb phase started from about 870 °C and consisted of two stages: (i) fast transformation of partially ordered β into O phase at higher temperatures followed by (ii) slow transformation of fully disordered β into O-phase at lower temperatures. The appearance of O-phase was accompanied by important volume decrease of the alloy as recorded using dilatometry as well as by a decrease of electrical resistivity. The transformations temperatures revealed by high energy X-ray diffraction, dilatometry and electrical resistivity were in good agreement. The obtained results were discussed using thermodynamic simulations carried out with Thermo-Calc software and TCTI2 database. • High temperature β phase is partially ordered with ordering degree of 0.6 at 1020 °C. • β phase undergoes slow disordering with temperature decrease followed by fast disordering when O-phase is formed. • O-phase formation consists into two stages with fast and slow kinetics depending on ordering of β phase. [ABSTRACT FROM AUTHOR]

Ambulatory cancer patients initiating chemotherapy are at increased risk of venous thromboembolism (VTE). The Khorana score (0 = low, 1-2 = intermediate, 3-6 = high) helps clinicians to stratify these patients according to their underlying risk of VTE. The CATS score, which incorporates additional points for elevated biomarkers (d-dimer, p-selectin), may enhance VTE risk stratification by adding up to two additional points to the Khorana score. We sought to evaluate the incidence of VTE in patients with a Khorana score of ≥ 2 and elevated biomarkers. The AVERT trial compared apixaban to placebo for the primary prevention of VTE in ambulatory cancer patients with a Khorana score of ≥ 2. D-dimer and p-selectin measurements were performed at randomization. Patients with d-dimer or p-selectin over the 75th percentile received 1 additional point each per elevated measurement (d-dimer ≥ 2.06 ug/mL and p-selectin ≥ 44.5 ng/mL). Cumulative 6-month VTE incidences according to Khorana and CATS scores were calculated using Kaplan-Meier analysis. VTE was assessed among patients receiving placebo (control group) according to modified intention to treat analysis, whereas bleeding events were assessed among patients receiving apixaban according to per-protocol analysis. For both the Khorana and CATS scores, the highest risk groups were merged into pooled high-risk groups (Khorana ≥ 3, CATS ≥ 4) given the low number of patients in higher risk strata. Hazard ratios for VTE were calculated by univariate and multivariable Cox regression analyses. The linear association between risk scores, VTE incidence and incidence of overall bleeding was tested for statistical significance. A total of 466 patients were included in the analysis, 229 and 237 patients in the placebo and apixaban arms, respectively. There were 73 (31.9%) and 86 (36.3%) patients with Khorana scores ≥ 3 in the control and apixaban arms, respectively, whereas there were 52 (22.7%) and 66 (27.9%) patients with CATS scores ≥ 4 in the control and apixaban arms, respectively. Mean age was 61.0 ± 11.8 and 60.6 ± 12.6 years in the control and apixaban arms, respectively. A minority of patients, 11.5% in the control arm and 15.1% in the apixaban arm, had ECOG scores of ≥ 2. The 6-month cumulative incidence of VTE was 13% (95% CI 7 to 23) in patients with a Khorana score of ≥ 3 and 20% (95% CI 11 to 35) in patients with a CATS score of ≥ 4, respectively. The linear trend for association of CATS risk scores with VTE was statistically significant (p = 0.0015). The linear trend for association of Khorana risk scores with VTE did not achieve statistical significance (p = 0.059). There was a total of 7 overall bleeding events (8.1%; 95% CI 2.4 to 13.9) in patients with a Khorana score of ≥ 3, two of which were major (2.3%; 95% CI 0 to 5.5). There were 7 overall bleeding events (10.6%; 95%CI: 3.2 to 18.0) in patients with a CATS score of ≥ 4, two of which were major (3.03%; 95%CI: 0 to 7.17). Neither increasing Khorana (p = 0.85, p = 0.69) or CATS scores (p = 0.58, p = 0.54) were significantly associated with either increased major or overall bleeding, respectively. Incorporation of d-dimer and p-selectin enhances VTE risk stratification in ambulatory cancer patients with a Khorana score of ≥ 2. [ABSTRACT FROM AUTHOR]

The article discusses case study of a 38-year-old woman having 5-6 weeks' of gestation with a history of abdominal discomfort. It is noted that the patient had a right ectopic pregnancy and salpingectomy and this pregnancy was being conceived by in vitro fertilisation. It is noted that the case study reveal problems associted with cornual ectopic pregnancies.

Introduction Cyclophosphamide-bortezomib-dexamethasone (CyBorD) is considered a standard induction regimen for transplant-eligible patients with newly diagnosed multiple myeloma (mm). It has not been prospectively compared with bortezomib-dexamethasone (Bor-Dex). We aimed to compare the efficacy of CyBorD and Bor-Dex induction in transplant-eligible patients. Methods In a retrospective observational study at a single tertiary centre, all patients with transplant-eligible mm who received induction with CyBorD or Bor-Dex between March 2008 and April 2016 were enrolled. Progression-free survival (pfs), response, and stem-cell collection for a first autologous stem-cell transplantation (ahsct) were compared. Results Of 155 patients enrolled, 78 (50.3%) had received CyBorD, and 77 (49.7%), Bor-Dex. The patients in the Bor-Dex cohort were younger than those in the CyBorD cohort (median: 57 years vs. 62 years; p = 0.0002) and more likely to have had treatment held, reduced, or discontinued (26% vs. 14.5%, p = 0.11). The stem-cell mobilization regimen for both cohorts was predominantly cyclophosphamide and granulocyte colony-stimulating factor (gcsf). Plerixa for was used more often for the CyBorD cohort (p = 0.009), and more collection failures occurred in the CyBorD cohort (p = 0.08). In patients receiving Bor-Dex, more cells were collected (9.9×106 cells/kg vs. 7.7×106 cells/kg, p = 0.007). At day +100, a very good partial response or better was achieved in 75% of the CyBorD cohort and in 73% of the Bor-Dex cohort (p = 0.77). Median pfs was 3.2 years in the Bor-Dex cohort and 3.7 years in the CyBorD cohort (p = 0.56). Conclusions Overall efficacy was similar in our patients receiving CyBorD and Bor-Dex. After ahsct, no difference in depth of response or pfs was observed. Cyclophosphamide-gcsf seems to increase collection failures and hospitalizations in patients receiving CyBorD. Prospective studies are required to examine that relationship. [ABSTRACT FROM AUTHOR]

To evaluate the clinical impact of the Canadian criteria for identifying patients and families at risk for hereditary renal cell carcinoma (RCC). The Canadian hereditary RCC risk criteria were applied to patients from 16 centres in the Canadian Kidney Cancer information system (CKCis) prospective database. The primary end point was the proportion of patients who met at least one criterion. Between January 2011 and May 2017, 8388 patients were entered in the database; 291 had inadequate risk data; 2827 (35%) met at least one criterion for genetic testing (at-risk population). Most (83%) met just one criterion. The criterion of non-clear cell histology contributed the largest proportion of at-risk patients (59%), followed by age ≤ 45 years (28%). Sixty-one patients had documentation of genetic testing, with 56 being classified at-risk (2% of at-risk). Twenty patients (35%) of the patients at risk and tested for hereditary RCC were found to harbour a germline mutation. Application of the Canadian hereditary RCC risk criteria to a large prospective database resulted in 35% of patients being identified at risk for hereditary RCC who could qualify for genetic testing. However, the true incidence of hereditary RCC in this population is unknown as most patients did not have documented genetic testing carried out and, thus, the sensitivity and specificity of the criteria cannot be determined. The low proportion of at-risk patients who underwent genetic testing is disappointing and highlights that there may be gaps in reporting, knowledge and/or barriers in access to genetic testing. • 2827 patients (35% of patients diagnosed with RCC) met the criteria for at risk for hereditary RCC. • 56 of the patients at risk were tested and 35% of them were found to harbour a germline mutation. • Low proportion of at-risk patients were referred for genetic testing. • Research is warranted to identify barriers to referrals and testing. [ABSTRACT FROM AUTHOR]

Background Diagnosis and treatment of renal cell carcinoma (rcc) might be different in Indigenous Canadians than in non-Indigenous Canadians. In this cohort study, we compared rcc presentation and treatments in Indigenous and non-Indigenous Canadians. Methods Patients registered in the Canadian Kidney Cancer Information System treated at 16 institutions between 2011 and 2018 were included. Baseline patient, tumour, and treatment characteristics were compared between Indigenous and non-Indigenous Canadians. The primary objective was to determine if differences in rcc stage at diagnosis were evident between the groups. The secondary objective was to determine if treatments and outcomes were different between the groups. Results During the study period, 105 of the 4529 registered patients self-identified as Indigenous. Those patients were significantly younger at the time of clinical diagnosis (57.9 ± 11.3 years vs. 62.0 ± 12.1 years, p = 0.0006) and had a family history prevalence of rcc that was double the prevalence in the non-Indigenous patients (14% vs. 7%, p = 0.004). Clinical stage at diagnosis was similar in the two groups (p = 0.61). The disease was metastatic at presentation in 11 Indigenous Canadians (10%) and in 355 non-Indigenous Canadians (8%). Comorbid conditions that could affect the management of rcc--such as obesity, renal disease, diabetes mellitus, and smoking--were more common in Indigenous Canadians (p < 0.05). Indigenous Canadians experienced a lower rate of active surveillance (p = 0.01). Treatments and median time to treatments were similar in the two groups. Conclusions Compared with their non-Indigenous counterparts, Indigenous Canadian patients with rcc are diagnosed at an earlier age and at a similar clinical stage. Despite higher baseline comorbid conditions, clinical outcomes are not worse for Indigenous Canadians than for non-Indigenous Canadians. [ABSTRACT FROM AUTHOR]

The article discusses case history of a 22-year-old woman with a 2-year history of an enlarged left labia minora and irritation of the vulva. It is noted that clinical examination revealed a hypertrophied left labia minora and histology depicted numerous parasitic ova with terminal spines suggesting presence of Schistosoma haematobium.

Purpose: The objective of this study is to determine primary survival endpoints in women with recurrent and metastatic endometrial carcinoma (RMEC) treated with progestins. Methods: A retrospective chart review was conducted at The Ottawa Hospital using electronic medical records. Inclusion criteria were a diagnosis of RMEC between 2000 and 2019, endometrioid histology, and ≥one line of progestin treatment. Progression‐free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results: Of 2342 cases reviewed, 74 met inclusion criteria. Sixty‐six (88.0%) patients received megestrol acetate and 9 (12.0%) received a progestin alternative. The distribution of tumors by grade was: 1: 25 (33.3%), 2: 30 (40.0%), and 3: 20 (26.7%). The PFS and OS for the entire study sample was 14.3 months (95% CI 6.2–17.9) and 23.3 months (14.8–36.8), respectively. The PFS for patients with Grade 1–2 RMEC was 15.7 months (8.0, 19.5), compared to 5.0 months (3.0, 23.0) with Grade 3 disease. The OS for patients with Grade 1–2 versus Grade 3, was 25.9 months (15.3, 40.3) versus 12.5 months (5.7, 35.9), respectively. Thirty‐four (45.9%) and 40 (54.1%) patients were treated with 0 and ≥1 line of chemotherapy. The PFS for chemotherapy‐naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following ≥1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy‐naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed. Conclusions: This real‐world data on RMEC suggests there is a role for progestins in select subgroups of women. The PFS for chemotherapy‐naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following ≥1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy‐OS was 29.1 months (17.9, 61.1) for chemotherapy‐naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed. This real‐world data on recurrent and metastatic endometrial carcinoma (RMEC) suggests there is a role for progestins in select subgroups of women. The PFS for chemotherapy‐naïve patients was 17.9 months (14.3, 27.0), versus 6.2 months (3.9, 14.8) following>=1 line of treatment. The OS was 29.1 months (17.9, 61.1) for chemotherapy‐OS was 29.1 months (17.9, 61.1) for chemotherapy‐naïve patients versus 23.0 months (10.5, 37.6) for patients previously exposed. [ABSTRACT FROM AUTHOR]

The primary aim was to assess if a clinical consensus regarding the management of pregnancy post myomectomy existed amongst consultant obstetricians and gynaecologists. Secondary objectives were to evaluate factors which influence the clinician's decision making in this group of women. Electronic survey sent to all consultants working in the North Central and East London deanery, Kent Surrey and Sussex deanery and Imperial NHS Trust to assess opinions on mode of birth post myomectomy, intervals advised to pregnancy post myomectomy, factors influencing the management of delivery in the scarred uterus post myomectomy, opinions on induction of labour and questions relating to operative notes. 209 consultant responses received between 07/03/2022–07/05/2022 (44% response rate); 77% (161/209) practicing obstetricians and gynaecologists, 10% (21/109) pure gynaecologists and 13% (27/209) pure obstetricians. The majority would support a vaginal birth after open myomectomy (75%) and laparoscopic myomectomy (79%). No consensus was found as to the optimal time interval between myomectomy and pregnancy. Higher frequency of performing myomectomy and a greater level of experience were significantly associated with a shorter interval to pregnancy advised. The most important operative factors influencing decision to support trial of labour post myomectomy were breach of uterine cavity; location of fibroids removed and number of incisions on the uterus. 77% believe women should be given a choice regarding mode of delivery post myomectomy in a similar way to previous LSCS. 82.8% would support enrolment of patients into a prospective trial to investigate delivery post myomectomy. We present a comprehensive survey of clinician opinions on pregnancy post myomectomy demonstrating that the majority of consultant obstetricians and gynaecologists sampled would support vaginal birth post myomectomy; counselling patients in a similar way to VBAC; a standardised myomectomy operation note and enrolment of patients in a future prospective trial. Wide variation in opinion regarding interval to pregnancy post myomectomy has been highlighted. We believe this information will facilitate counselling discussions and empower women with subsequent pregnancies after myomectomy to make an informed decision on mode of birth post myomectomy. [ABSTRACT FROM AUTHOR]

The agronomic performance of 18 M4 generation mutants of aromatic rice (Oryza sativa L.) was evaluated along with their two mother genotypes, IET 14142 and IET 14143. IET 1412 and IET14143 were developed from Tulaipanja, an aromatic non-basmati rice cultivar, popularly grown in northern parts of West Bengal - an important rice growing province of India. The results indicate that there is a considerable amount of genetic variability among mutants with respect to thirteen quantitative characters. Some of the mutants had a combination of both positive and negative forms of important yield contributing characters. The performance of four mutants (T1m1, T1m6, T2m4 and T2m8) indicated considerable improvement in grain yield over their respective control. The increased grain yield per plant in the above high yielding mutants is primarily due to increase in panicle number per plant, spikelet number per panicle, grain number per panicle and test weight. These mutants need further evaluation in multilocation trials to judge their potential as varieties of aromatic rice. The other mutants may be used in cross-breeding programmes of aromatic rice for agronomically useful characters i.e., early flowering, short stature, erect flag leaf, high grain number, heavy weight per 100 grains. The apparent changes in different characters in an individual mutant may not be due to genetic changes in all the affected characters. The possible role of pleiotropic effects of mutant genes cannot be ruled out. [ABSTRACT FROM AUTHOR]

It is now possible to search for new drugs using high-throughput screening of chemical libraries accumulated over the past few years. To detect potential new hyperthermia sensitizers, we are screening for chemical inhibitors of thermotolerance. For the screening of a large chemical library, a rapid and simple assay based on the XTT-tetrazolium salt with the addition of intermediate electron acceptor, phenazine methosulphate (PMS) as a promoter, was developed. It was found that the sensitivity of the XTT/PMS assay is sufficient for assessing thermal cell killing and thermotolerance, although it was highly dependent on cell number and type. When the formazan assay system was challenged with the bioflavonoid drug quercetin (up to 25mm) and validated against the clonogenic cell survival assay, significant decreases in thermotolerant cell viability were observed, directly reflecting inhibition of thermotolerance. Although short-term assays can, in some instances, underestimate overall cell killing, the dose dependency of inhibition of thermotolerance by quercetin recorded in this study by clonogenic and XTT/PMS assays was similar. Application of the XTT/PMS assay in chemical library screening was highly effective in differentiating potential thermotolerance inhibitors from both chemicals with lack of efficacy and from toxic compounds. Taken together, these results show that the XTT/PMS assay, when carried out under careful conditions, is well suited for primary high-flux screen of many thousands of compounds, thus opening up new areas for discovery of hyperthermia sensitizers. [ABSTRACT FROM AUTHOR]

Background: Prevention of TB is paramount to achieving elimination targets as recommended by the World Health Organization's action framework for low incidence countries striving to eliminate TB. Although the rates of TB in Canada are low, understanding the latent TB infection (LTBI) cascade is paramount to identifying gaps in care and treatment barriers, thereby increasing the effectiveness of preventive strategies. The purpose of this study was to examine the LTBI cascade of care and identify barriers to treatment completion in adults referred from primary care to a regional tertiary care TB clinic in Ottawa, Canada.Methods: Electronic medical records between January 2010 and December 2016 were reviewed retrospectively and an LTBI cascade of care was constructed from The Ottawa Hospital TB clinic and surrounding primary care clinics. A cohort of 2207 patients with untreated LTBI was used to ascertain the associations between demographic and clinical factors for both treatment non-initiation and non-completion using log-binomial univariable and multivariable regression models.Results: Of 2207 patients with untreated LTBI who were seen in the clinic during the study period, 1771 (80.2%) were offered treatment, 1203 (67.9% of those offered) started treatment, and 795 (66.1% of those started) completed treatment. In multivariable analysis, non-initiation of treatment was associated with older age (adjusted risk ratio [aRR] 1.06 per 5-year increase, 95% CI: 1.03-1.08) and female gender (aRR 1.28, 95% CI: 1.11-1.47). Non completion of treatment was associated with referral from the TB Clinic back to the primary care team following initial consult (aRR 1.62, 95% CI: 1.35-1.94) and treatment with the standard of 9 months of Isoniazid (9H) compared to 4 months of Rifampin (4R) (aRR 1.45, 95% CI:1.20-1.74).Conclusions: LTBI treatment completion was significantly decreased among patients who were referred back to primary care from the TB clinic. The 4R regimen resulted in more people completing LTBI treatment compared to 9H in keeping with a recently published RCT. Improved education, communication, and collaboration between tertiary care TB clinics and primary care teams may improve treatment completion rates and address the TB burden in low incidence communities in Canada. [ABSTRACT FROM AUTHOR]

The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer patients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days. In this randomised, open-label trial, early breast cancer patients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles. A protocol amendment in November 2017 allowed subsequent patients (N = 324) to be randomised to either 5 or 7/10 days. The primary outcome was a composite of either FN or treatment-related hospitalisations. Secondary outcomes included chemotherapy dose reductions, delays and discontinuations. Analyses were carried out by per protocol (primary) and intention-to-treat, and the non-inferiority margin was set at 3% for the risk of having FN and/or hospitalisation per cycle of chemotherapy. Patients (N = 466) were randomised to receive 5 (184, 39.5%), or 7/10 (282, 60.5%) days of filgrastim. In our primary analysis, the difference in risk of either FN or treatment-related hospitalisation per cycle was −1.52% [95% confidence interval (CI): −3.22% to 0.19%] suggesting non-inferiority of a 5-day filgrastim schedule compared with 7/10-days. The difference in events per cycle for FN was 0.11% (95% CI: −1.05 to 1.27) while for treatment-related hospitalisations it was −1.68% (95% CI: −2.73% to −0.63%). The overall proportions of patients having at least one occurrence of either FN or treatment-related hospitalisation were 11.8% and 14.96% for the 5- and 7/10-day groups, respectively (risk difference: −3.17%, 95% CI: −9.51% to 3.18%). Five days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days should be considered standard of care. NCT02428114 and NCT02816164. • Multicentre randomised trial of 466 breast cancer patients compared schedules of filgrastim administration. • Provides real-world data showing filgrastim use beyond 5 days did not significantly improve co-primary or secondary outcomes. • 5 days of filgrastim should be considered the standard of care. [ABSTRACT FROM AUTHOR]

Sunflower, an important oil seed crop, needs a balanced nutrition for its optimum growth and thorough maintenance of soil health. A field experiment was conducted to study the impact of integrated use of organic, inorganic and biofertilizers on soil fertility, soil organic carbon fractions, soil microbiological and biochemical parameters as well as yield of sunflower (cv. GK 2002) in alluvial soil at Agricultural Experimental Farm, University of Calcutta, Baruipur, India, during 2013-14 and 2014-15. There were ten different treatments with three replications. After analysis, the data clearly showed significant difference among treatments in sunflower yield and a prominent impact of integrated use of organic, inorganic and biofertilizers was found under the treatments. Microbial biomass carbon, basal soil respiration, activities of soil enzyme and different carbon fractions showed higher values for those treatments where only organic inputs were given. The best possible combination for higher seed yield was recorded in T10/T6 treatment (vermicompost 2.5 t ha-1 or FYM (5 t ha-1) with phosphate solubilizing bacteria @ 8 kg ha-1 soil application + Azotobacter @ 8 kg ha-1 soil application + 50% recommended dose of chemical fertilizers + foliar spray (2% urea)). T10/T6 treatment is thus recommended for sunflower cultivation in alluvial soil considering the soil quality and seed yield of sunflower. [ABSTRACT FROM AUTHOR]

Effects of steady-state rifabutin on the pharmacokinetics of steady-state maraviroc were investigated in fourteen healthy adult female and male volunteers. Maraviroc 300 mg twice daily (BID) was given orally with food for fifteen days. On day six, rifabutin 300 mg once daily (QD, P.O.) was added to the regimen. Formal pharmacokinetic (PK) sampling was performed on days five and fifteen. Individual plasma drug concentration-time data for maraviroc, and rifabutin on day fifteen, were obtained using validated High Performance Liquid Chromatography (HPLC) tandem Mass Spectrometry (MS/MS). Rifabutin steady state exposure was comparable to data in the literature. Maraviroc area under the curve (AUC) and minimum plasma concentration (Clast or Cmin) were reduced by 17% and 30% respectively when co-administered with rifabutin. No unexpected or serious adverse eventsoccurred. Based on the reduced exposure of maraviroc observed in this study, increasing the dose of maraviroc may be studied to normalize its moderately reduced exposure following rifabutin co-administration, a moderate inducer of CYP3A4. [ABSTRACT FROM AUTHOR]

Background: The purpose of this randomised double-blind double-dummy placebo-controlled trial was to investigate whether etanercept, a tumour necrosis factor α (TNFα) antagonist, would provide more effective anti-inflammatory treatment for acute exacerbations of chronic obstructive pulmonary disease (COPD) than prednisone.Methods: We enrolled 81 patients with acute exacerbations of COPD and randomly assigned them to treatment with either 40 mg oral prednisone given daily for 10 days or to 50 mg etanercept given subcutaneously at randomisation and 1 week later. Both groups received levofloxacin for 10 days plus inhaled bronchodilators. The primary endpoint was the change in the patient's forced expiratory volume in 1 s (FEV(1)) 14 days after randomisation. Secondary endpoints included 90-day treatment failure rates and dyspnoea and quality of life.Results: At 14 days the mean±SE change in FEV(1) from baseline was 20.1±5.0% and 15.2±5.7% for the prednisone and etanercept groups, respectively. The mean between-treatment difference was 4.9% (95% CI -10.3% to 20.2%), p=0.52. Rates of treatment failure at 90 days were similar in the prednisone and etanercept groups (32% vs 40%, p=0.44), as were measures of dyspnoea and quality of life. Subgroup analysis revealed that patients with serum eosinophils >2% at exacerbation tended to experience fewer treatment failures if treated with prednisone compared with etanercept (22% vs 50%, p=0.08).Conclusions: Etanercept was not more effective than prednisone for treatment of acute exacerbations of COPD. Efficacy of prednisone was most apparent in patients who presented with serum eosinophils >2%.Clinical Trials: gov number NCT 00789997. [ABSTRACT FROM AUTHOR]

A versatile system has been designed and fabricated to prepare atom-probe field-ion-microscope (APFIM) specimens in a systematic manner, such that internal interfaces can be positioned in the tips of these wire specimens for subsequent analysis of their chemical composition. This system incorporates both beaker electrolytic and zone electrolytic cell configurations, a specially constructed power supply, and a special transmission electron microscope holder for wires. The power supply enables ac electroetching or dc electropolishing in the automated or manual modes. The ac wave forms available are sine (0.002 Hz–200 kHz) or square (10 Hz–20 kHz). Triggering and gating are performed manually or with a pulse generator. The dc output is gated manually to produce a continuous output or with a pulse generator to produce single pulses with widths in the range 50 μs–1 s. A counter indicates the number of periods of voltage applied, and the total charge transferred in the electrolytic cell is integrated in the range 10 μA s–1 kA s. The power supply provides 0 to ±48 V peak at 1 A peak. A double-tilt stage for an Hitachi H-700H 200 kV transmission electron microscope (TEM) was radically modified to hold APFIM specimens; this stage is vibrationless at 310 000× magnification. It has a tilting range of ±30° and ±27° for the x and y tilts, respectively. Examples are given of the controlled backpolishing of W-3 at. % Re, W-25 at. % Re, Mo-5.4 at. % Re, and Fe-3 at. % Si specimens, and their observation by TEM, to selectively place grain boundaries in the tip region. The analysis of the chemical composition of a grain boundary, which is first located in a W-25 at. % Re specimen via TEM, by the APFIM technique is presented. [ABSTRACT FROM AUTHOR]

Background: Optimal bisphosphonate (BP) dosing intervals for breast cancer patients (pts) with bone metastases (BM) remain unknown. BP are usually prescribed q3-4 wk regardless of individual pt risk for skeletal related events (SREs). Recent evidence (Amadori J Clin Oncol, 2012 suppl; abstr 9005) shows that q12 wk BP is as effective as q4 wk in pts previously treated with >9 cycles of q4 wk therapy. Hence, further evaluation of modified BP dosing strategies is warranted. The objective of the current study was to show in women with biochemically defined low-risk bone disease that IV BP use every q12 wk for 1 year is sufficient to maintain stability of the bone turnover [measured by serum ctelopeptide (CTx) or bone specific alkaline phosphatase (BSAP)]. Methods: Eligible pts with BM, who had received >3 months of q3-4 wk IV BP and no systemic treatment change within 4 wks of study entry were enrolled. Low risk was defined as serum CTx <600 ng/L. Biochemical failure was defined as CTx levels >600 ng/L at baseline, weeks 6, 12, 24, 36 or 48. Evaluation of palliative benefit of 12-wk IV BP therapy was measured by SREs, analgesic use, and self-reported pain (BPI and FACT-BP). Results: Between Oct. 2010-Sept. 2011, 85 pts consented to screening, with 13 found ineligible. In the 71 accrued pts baseline characteristics were: mean age 60 (SD 13), median time from breast cancer diagnosis to development of bone metastases 4 months (IQR 82), median duration of prior BP therapy 14 months (IQR 19), and mean number of SREs/yr prior to entering study 0.35 (SD 0.76). Baseline median CTx was 120 ng/L (IQR 240) and BSAP 9.2 IU/L (IQR 3). To date: 26/71 pts (36%) remain on study. Reasons for coming off study include; study completion (18), elevation of CTx >600ng/L (10), or on study SRE (3). An elevation of CTx between baseline and wk 6 was significantly associated with coming off study early (p = 0.008). For pts who had had an SRE before study entry the odds ratios for coming off study early due to an on study SRE or elevated CTx was 1.005 (CI 1.002-1.009; p = 0.007) and for coming off early for an SRE was 0.0245 (CI 0.061-0.094; p = 0.046) respectively. Of the 8/13 pts who were ineligible due to baseline CTx >600ng/L, 6 had an SRE within 1 year of screening. Conclusion: De-escalating BP therapy to 12 weekly in low risk pts has advantages for both the pt and the health care system. Individual risk of SREs is highly variable, however baseline serum CTx levels <600 ng/L is associated with a low risk of subsequent SREs. While larger trials are required to assess whether increasing CTx with de-escalated therapy will lead to higher rates of SREs or not (Coleman et al. J Clin Oncol 2012 suppl; abstr 511). However, the results of this study and Amadori et al. would suggest that de-escalated BP treatment will likely become a new standard of care after a limited period of q 4wk treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Despite considerable variability in patient (pt) risk of skeletal related events (SREs) from bone metastases (BM), all pts are treated using a one size fits all approach, namely the same dose and dosing schedule (q3-4 wk) of IV bisphosphonate (BP). Identification of novel markers of individual SRE risk are thus required to better tailor treatment. TRIUMPH is an ongoing clinical trial evaluating q12 wk IV BP therapy for 1 year, following >3 months of standard q3-4 wk BP, in women with low risk bone metastases [defined by the bone resorption marker C-telopeptide (CTx) levels <600 ng/L]. This sub-study evaluated the utility of novel biomarkers in better predicting SRE risk in this low-risk cohort. METHODS: Seventy-one pts enrolled in TRIUMPH. Pt serum at baseline (69), 6 (67) and 12 (59) wks post-entry were analyzed for CTx and bone-specific alkaline phosphatase (BSAP) as per study protocol. Urine N-telopeptide (NTx) levels and serum levels of transforming growth factor-ß (TGF-ß), activinA, procollagen type I amino-terminal propeptide (P1NP), and bone sialoprotein (BSP) levels were also assessed by ELISA (for n=63, 63 and 57 patients at baseline, wk 6 and wk 12 respectively). Biomarker levels were correlated with pt parameters including; time to development of BM, previous SREs, and SREs post-study entry using linear regression analysis. Changes in levels of biomarkers from baseline to 6 or 12 weeks were used to calculate odds ratios of coming off study as per protocol (due to either CTx>600 ng/ml or SRE) or of SRE alone using logistic regression analysis. RESULTS: Although baseline CTx and NTx were elevated in pts who went on to develop SREs, this did not reach statistical significance. Baseline activinA trended towards total number of prior SREs (p = 0.07). Baseline TGF-ß correlated with duration of BM (p = 0.004). Change in activinA (baseline to week 6) was the only biomarker that trended to predict coming off study early (p = 0.043). Results of other baseline biomarkers and changes in biomarkers from baseline to wk 12 will also be presented. CONCLUSIONS: This study further questions the role of CTx and NTx for driving treatment decisions around de-intensification of BP therapy (Coleman et al. J Clin Oncol 2012, suppl; abstr 511), and highlights the need for novel markers of SRE risk. Baseline levels of activinA was associated with the incidence of SREs in patients with BM and changes in levels from baseline to 6 weeks correlated with coming off study early. These findings warrant future studies in breast cancer pts assessing activinA as a predictor of SRE risk associated with breast cancer bone metastases. This study was supported by grants from the Ontario Institute for Cancer Research with funding from the Government of Ontario, and from the Ontario Chapter of the Canadian Breast Cancer Foundation. [ABSTRACT FROM AUTHOR]

Background: Despite variability in an individual's risk of skeletal related events (SREs) from bone metastases (BM), all patients are treated using a similar dose and schedule (q3-4 wk) of IV bisphosphonate (BP). The REFORM trial (Amir et al., Am J Clin Oncol, in press) was a pilot randomised study evaluating the efficacy of de-escalated (q12 wk) versus standard (q3-4 wk) pamidronate in maintaining C-telopeptide (CTx) levels in the low risk range (<600ng/L) in patients with BM from breast cancer. Here we report a biomarker substudy, where additional biomarkers of bone turnover and BM behaviour were measured and correlated with SRE risk. Methods: Eligible patients with BM, who had received 3 months of q3-4 wk IV BP and no systemic treatment change within 4 wks of study entry were enrolled. Serum & urine obtained at baseline and at 12 wks were assessed for urinary N-telopeptide (uNTx), serum procollagen type I amino-terminal propeptide (P1NP), transforming growth factor (TGF)-ß, activinA and bone sialoprotein (BSP) by ELISA. Levels were correlated with number of SREs using linear regression analysis. Changes in biomarkers from baseline to 12 wks were used to calculate odds ratios for coming off study (due to either elevated CTx or SRE) or having an SRE alone using logistic regression analysis. Results: REFORM randomized 19 patients to each treatment arm, and found that the SRE rate at 1 year in both arms was the same (n = 2). Although the mean level of the standard bone turnover marker CTx decreased slightly from baseline to wk 12 in the q3-4 wk group (240±50ng/L to 206±46ng/L), and slightly increased in the q12 wk treated group (263±65ng/L to 313±71ng/L), these changes were not statistically significant (p = 0.8). Mean activinA levels were slightly increased in both treatment arms from baseline to wk 12 (730±93pg/ml to 875±148pg/ml in q3-4 wk group vs 445±35pg/ml to 582±61pg/ml in q12 wk group) but did not quite reach statistical significance (p = 0.1). Levels of TGF-ß from baseline to 12 wks in both groups was similar (22±1.6ng/ml to 22±2.3ng/ml for q3-4 wk vs 23±2.2ng/ml to 24±2.4ng/ml for q12 wk group, p = 0.8). Although the number of SREs was small, mean CTx levels at wk 12 were statistically different between patients who experienced SREs vs those that did not (615±72ng/L, n=4 vs 190±26ng/L, n=19, p < 0.0001). Although it did not reach statistical significance, mean activinA levels at wk 12 were also higher in patients who had SREs than those that did not (1069±358pg/ml, n=3 vs 681±83pg/ml, n=18, p = 0.12). Results of NTx, BSP and P1NP and correlations with more mature clinical data will also be presented. Conclusions: In patients with BM from breast cancer with low levels of bone resorption markers, CTx predicted and activinA trended to predict SRE risk. However the non-significant trends in increasing CTx in de-escalated BP treatment, together with the observation that activinA levels are similar regardless of dosing regimen, suggest that analysis of conventional and experimental biomarkers of SRE risk requires further examination in other larger patient cohorts comparing de-escalated therapy. [ABSTRACT FROM AUTHOR]