Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices.

BACKGROUND: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice. METHODS: A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice. RESULTS: A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P = 0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P = 0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P = 0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P = 0.013). Survival was similar in both arms. CONCLUSION: The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com).

Nurse-led general surgical pre-operative assessment clinic.

A nurse-led Pre-operative Assessment Clinic was introduced into the General Surgical Directorate at the Royal Hallamshire Hospital in August 1993 to provide a general medical and anaesthetic pre-operative assessment, to give information, both written and verbal, to patients about their operations and to identify social problems which might delay discharge. Patients were seen either at the time of their original clinic appointment or subsequently on a recall basis, prior to admission to hospital. The clinic was run by two out-patient nurses working to agreed protocols. Patients were given written information leaflets in addition to a verbal explanation about their admission and operation. In order to assess the effectiveness of the clinic, a group of patients attending during the first year were compared with similar patients who did not undergo pre-operative assessment. A questionnaire of satisfaction with information received was completed and compliance with the clinic protocols was recorded. In the pre-operative assessment group, patients were more satisfied with the amount of information received and there were significantly fewer cancellations due to unforseen medical problems in this group. Eighteen per cent of investigations were repeated unnecessarily because the reports were unavailable or considered out of date. However, only 1% of patients pre-operatively assessed had their operations cancelled after their admission, compared with 6% of non pre-operatively assessed patients. Given the total number of patients admitted for surgical procedures per year, the introduction of comprehensive pre-operative assessment for all patients could result in a substantial reduction in cancellations following admission.

Luminal acidification in K-replete OMCDi: inhibition of bicarbonate absorption by K removal and luminal Ba.

We have previously demonstrated that significant luminal acidification in the K-replete rabbit inner stripe of the outer medullary collecting duct (OMCDi) occurs via a renal H-K-adenosinetriphosphatase (H-K-ATPase) sensitive to several of the gastric H-K-ATPase inhibitors. To investigate further the mechanism of K-dependent luminal acidification in K-replete OMCDi, we examined the effects of luminal K removal, luminal addition of Ba in the presence and absence of luminal 5.0 nM bafilomycin A1 (BAF), and basolateral addition of Ba on net bicarbonate flux (JtCO2, pmol.mm-1.min-1) and transepithelial voltage (VT, mV). Removal of K from the perfusate inhibited JtCO2 by 74% (13.4 +/- 4.0 for control, 3.5 +/- 1.4 pmol.mm-1.min-1 for experimental, P < 0.05) and was statistically equivalent to the degree of inhibition previously observed under identical experimental conditions by either 10 microM Sch-28080 or 10 microM A-80915A. Approximately 50% inhibition of JtCO2 was observed following luminal application of 2.0 mM Ba2+, and the degree of inhibition was statistically equivalent regardless of whether BAF was present (12.2 +/- 2.7 for control, 6.0 +/- 1.4 pmol.mm-1.min-1 for 2.0 mM Ba2+, P < 0.05; 9.6 +/- 1.2 for control with 5 nM BAF, 5.7 +/- 1.3 pmol.mm-1.min-1 for 2.0 mM Ba2+ with 5 nM BAF, P < 0.05). Additionally, increasing the luminal concentration of Ba2+ from 2.0 to 4.0 mM resulted in no further inhibition of JtCO2 (8.5 +/- 1.7 for control, 3.9 +/- 1.3 pmol.mm-1.min-1 for 4.0 mM Ba2+, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Luminal acidification in K-replete OMCDi: contributions of H-K-ATPase and bafilomycin-A1-sensitive H-ATPase.

We have previously demonstrated that basolateral addition of the gastric H-K-adenosinetriphosphatase (H-K-ATPase) inhibitor Sch-28080 (10 microM) profoundly reduced net total CO2 flux (JtCO2) in the inner stripe of the outer medullary collecting duct (OMCDi) of K-replete rabbits. In the present studies, we first addressed whether the inhibitory effect of Sch-28080 is dependent on the side of the membrane to which it is added. Second, we reassessed the relative magnitude of contribution of H-K-ATPase. Third, we formally tested whether a bafilomycin-A1 (BAF)-sensitive H-ATPase also contributes to luminal acidification in the OMCDi under K-replete dietary conditions. We found that luminal addition of the structurally and functionally dissimilar gastric H-K-ATPase inhibitor A80915A (10 microM) profoundly reduced JtCO2 while transepithelial voltage (VT) was unchanged. This degree of inhibition was statistically indistinguishable from our previous results when Sch-28080 was applied basolaterally. Inhibition of JtCO2 by the less membrane-permeable N-methyl cation of Sch-28080, H224/25, was significant when applied luminally but was not significant when applied basolaterally. VT was not significantly affected by either the luminal or basolateral addition of H224/25. To evaluate the possible contribution of an H-ATPase, the effect of both 5.0 nM and 10.0 nM luminal BAF on JtCO2 and VT was examined. At 5.0 nM, BAF significantly inhibited JtCO2). However, this observation was significantly less (P < 0.05) than the inhibition observed with 10 microM A80915A. No additional inhibition was observed by increasing the concentration of BAF to 10.0 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

Dust from cotton manufacture: changing from static to personal sampling.

Several designs of personal samplers were tested for use to collect cotton dust. The IOM personal inhalable-dust sampler was selected because: (1) collection of the whole inhalable fraction was preferred, since all inhaled sizes are under suspicion as contributing to respiratory symptoms in cotton exposure; (2) this sampler is well characterized; and (3) it was found to be practicable in the environments examined. Gauze shields to exclude 'fly' from the personal sampler were tried, but were rejected mainly because measurement of the whole inhalable fraction by a validated sampler was felt to be more appropriate. A range of processes at a representative selection of mills was assessed by a hygiene team, and classified as 'clean' or 'dirty' in terms of present standards of control. This classification agreed well with subsequent measurements using the present method, which uses a large static sampler. A personal sampling survey then showed that in about two-thirds of 'clean' processes personal exposure of at least 80% of those employed was less than about 2-2.5 mg m-3. Only one-tenth of 'dirty' processes met this standard. Personal exposure correlates poorly with the present static method, as expected, but comparison of the results suggested that a mean background level of 0.5 mg m-3 would correspond to a median personal exposure of about 2.2 mg m-3. Side-by-side measurements by the background method differed by less than 0.15 mg m-3 on about 95% of occasions. Niven et al. (to be published) have compared the IOM head used in this study with the Manchester University sampler previously used by Cinkotai et al. [Ann. occup. Hyg. 32, 103-113 (1988)] to derive a relationship between personal exposure and prevalence of byssinotic symptoms in spinners. According to Cinkotai et al.'s results the concentrations of 2-2.5 mg m-3 discussed would correspond to a prevalence of 3-5%. However, this prevalence probably reflects higher exposures in the past.

Rubidium absorption and proton secretion by rabbit outer medullary collecting duct via H-K-ATPase.

Multiple lines of evidence support the hypothesis that the outer medullary collecting duct from the inner stripe (OMCDi) possesses a functional proton-potassium-activated adenosinetriphosphatase (H-K-ATPase). To examine the effect of inhibition of H-K-ATPase on Rb efflux, we measured the Rb tracer rate efflux coefficient (KRb) across the OMCDi of animals adapted to a K-restricted diet using the selective K-competitive H-K-ATPase inhibitor, Sch 28080. Sch 28080 (10 microM) did not significantly alter transepithelial voltage (VT) but significantly decreased KRb by 41%. We further examined the effect of 10% peritubular CO2 on KRb and the subsequent effect of Sch 28080 (10 microM) on KRb. After exposure to 10% CO2 for 120 min, vehicle-treated tubules exhibited a small but significant increase in KRb without a significant change in VT. In contrast, 10 microM Sch 28080 significantly decreased KRb by 44% without affecting VT. The lack of an effect of H-K-ATPase inhibition on VT in the presence of either 5% or 10% CO2 was in marked contrast to the effect of carbonic anhydrase inhibition (CAI). CAI consistently and significantly decreased VT either in the presence of 5% or 10% CO2. To address whether H-K-ATPase also participates in proton secretion we examined the effect of Sch 28080 (10 microM) on net bicarbonate absorption by the OMCDi of rabbits fed a normal rabbit ration and rabbits adapted to a K-restricted diet.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo MR evaluation of Gd-DTPA conjugated to dextran in normal rabbits.

A dextran-Gd-DTPA compound has been recently synthesized utilizing 70,800 Da molecular weight dextran. This polymeric contrast agent for magnetic resonance imaging has been found chemically to be very stable and to demonstrate in vitro improved relaxivities of 1.5 to 2.3 times that of monomeric Gd-DTPA at 100 MHz. This MR experiment examines the in vivo distribution and relaxivity of the 70,800 Da molecular weight dextran-Gd-DTPA compound in a rabbit model by measuring the change in signal-to-noise ratio of a variety of organs (renal cortex, renal medulla, liver, brain, and torcula herophile) compared to the preinjection state. Results demonstrate prolonged (beyond 60 min) enhancement of the renal cortex, renal medulla, liver and torcula, and no enhancement of brain parenchyma.

Polymeric contrast agents for magnetic resonance imaging: synthesis and characterization of gadolinium diethylenetriaminepentaacetic acid conjugated to polysaccharides.

The synthesis and characterization of polysaccharides esterified with gadolinium diethylenetriaminepentaacetic acid (GdDTPA) are described. The results of several synthetic methods are presented for esterification of dextrans and inulin with DTPA. One method results in highly conjugated products labeled with an average of 0.4 mol of GdDTPA/mol of glucopyranose unit in dextrans of up to 70,800 average molecular weight and 0.5 mol of GdDTPA/mol of fructofuranose unit in inulin. Chromatographic and potentiometric evidence supporting the absence of significant chelate cross-linking of the conjugated polysaccharides is presented. The thermodynamic stability constant, log K (Gd3+ + L4(-)----GdL-), of the complexes was 18.0 +/- 0.2 based on an independent chelate model. In vitro ester hydrolysis of the GdDTPA-dextran 70,800 (at 37 degrees C, pH = 7.4 phosphate buffer) occurs with a half-life of 21 h. The agents exhibit T1 relaxivities ranging from 1.5 to 2.3 times that of GdDTPA at 100 MHz, and decreasing in vitro relaxivity with increasing molecular weight of the dextran carrier was observed. Phantom MRI studies indicate that the T1 and T2 effects of the complexes differ from those of GdDTPA, with the polysaccharide-bound complexes exhibiting a considerably faster drop in relative signal intensity with increased concentration in T1 and T2 weighted pulse sequences.