Pacemaker Use in New Zealand - Data From the New Zealand Implanted Cardiac Device Registry (ANZACS-QI 15).

BACKGROUND: The New Zealand Cardiac Implanted Device Registry (Device) has recently been developed under the auspices of the New Zealand Branch of the Cardiac Society of Australia and New Zealand. This study describes the initial Device registry cohort of patients receiving a new pacemaker, their indications for pacing and their perioperative complications. METHODS: The Device Registry was used to audit patients receiving a first pacemaker between 1st January 2014 and 1st June 2015. RESULTS: We examined 1611 patients undergoing first pacemaker implantation. Patients were predominantly male (59%), and had a median age of 70 years. The most common symptom for pacemaker implantation was syncope (39%), followed by dizziness (30%) and dyspnoea (12%). The most common aetiology for a pacemaker was a conduction tissue disorder (35%), followed by sinus node dysfunction (22%). Atrioventricular (AV) block was the most common ECG abnormality, present in 44%. Dual chamber pacemakers were most common (62%), followed by single chamber ventricular pacemakers (34%), and cardiac resynchronisation therapy - pacemakers (CRT-P) (2%). Complications within 24hours of the implant procedure were reported in 64 patients (3.9%), none of which were fatal. The most common complication was the need for reoperation to manipulate a lead, occurring in 23 patients (1.4%). CONCLUSION: This is the first description of data entered into the Device registry. Patients receiving a pacemaker were younger than in European registries, and there was a low use of CRT-P devices compared to international rates. Complications rates were low and compare favourably to available international data.

Dual neurocircuitry dysfunctions in disruptive behavior disorders: emotional responding and response inhibition.

BACKGROUND: To determine the functional integrity of the neural systems involved in emotional responding/regulation and response control/inhibition in youth (age 10-18 years) with disruptive behavioral disorders (DBDs: conduct disorder and/or oppositional defiant disorder) as a function of callous-unemotional (CU) traits. METHOD: Twenty-eight healthy youths and 35 youths with DBD [high CU (HCU), n = 18; low CU (LCU), n = 17] performed the fMRI Affective Stroop task. Participants viewed positive, neutral, and negative images under varying levels of cognitive load. A 3-way ANOVA (group×emotion by task) was conducted on the BOLD response data. RESULTS: Youth with DBD-HCU showed significantly less activation of ventromedial prefrontal cortex (vmPFC) and amygdala in response to negative stimuli, compared to healthy youth and youth with DBD-LCU. vmPFC responsiveness was inversely related to CU symptoms in DBD. Youth with DBD-LCU showed decreased functional connectivity between amygdala and regions including inferior frontal gyrus in response to emotional stimuli. Youth with DBD (LCU and HCU) additionally showed decreased insula responsiveness to high load (incongruent trials) compared to healthy youth. Insula responsiveness was inversely related to ADHD symptoms in DBD. CONCLUSIONS: These data reveal two forms of pathophysiology in DBD. One associated with reduced amygdala and vmPFC responses to negative stimuli and related to increased CU traits. Another associated with reduced insula responses during high load task trials and related to ADHD symptoms. Appropriate treatment will need to be individualized according to the patient's specific pathophysiology.

Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis.

Post-traumatic arthritis (PTA) is a rapidly progressive form of arthritis that develops due to joint injury, including articular fracture. Current treatments are limited to surgical restoration and stabilization of the joint; however, evidence suggests that PTA progression is mediated by the upregulation of pro-inflammatory cytokines, such as interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α). Although these cytokines provide potential therapeutic targets for PTA, intra-articular injections of anti-cytokine therapies have proven difficult due to rapid clearance from the joint space. In this study, we examined the ability of a cross-linked elastin-like polypeptide (xELP) drug depot to provide sustained intra-articular delivery of IL-1 and TNF-α inhibitors as a beneficial therapy. Mice sustained a closed intra-articular tibial plateau fracture; treatment groups received a single intra-articular injection of drug encapsulated in xELP. Arthritic changes were assessed 4 and 8 weeks after fracture. Inhibition of IL-1 significantly reduced the severity of cartilage degeneration and synovitis. Inhibition of TNF-α alone or with IL-1 led to deleterious effects in bone morphology, articular cartilage degeneration, and synovitis. These findings suggest that IL-1 plays a critical role in the pathogenesis of PTA following articular fracture, and sustained intra-articular cytokine inhibition may provide a therapeutic approach for reducing or preventing joint degeneration following trauma.

Thermoluminescent composites of sintered synthetic-topaz/in situ corundum for dosimetry by a novel reversible process.

Topaz (Al2F1·44(OH)0·56SiO4)/corundum (Al2O3) composites were prepared by a facile and novel reversible process from the sintering of synthetic topaz and AlF3 powders, with corundum formed in situ into the topaz matrix. The corundum formation reaction occurs in the temperature range 875-975 °C, from 40 min sintering time, obtaining the topaz- Al2F1·44(OH)0·56SiO4/corundum- Al2O3 composites. Although sintering temperature and time increment lead to higher corundum formation in the topaz matrix (78.4 wt % Al2O3 at 975 °C for 60 min), longer residence times give place to corundum percentage decrease due to topaz reconversion. The composites' microstructure is characterized by a rectangular bar with stacked pyramidal ends and polycrystals of hexagonal plates for topaz and corundum, respectively. For the topaz/corundum composites, the maximum density was 3.05 g/cm3 (17 % porosity) for specimens sintered at 925 °C for 20 min. The glow curves of the topaz/in situ corundum composite sintered at 975 °C and 0 min dwell time show thermoluminescent peaks between 180 and 250 °C, useful for dosimetric applications. The most helpful peak (at 221 °C) in the topaz/corundum composite's glow curves determined by computational deconvolution is sharp and exhibits the highest thermoluminescent response. Dose-response analysis of the composite (sintered at 975 °C for 0 min) with the best thermoluminescent response revealed two ranges of linear behavior, the first from 2 to 200 mGy, with an adjustment of 99.9 % and the second in the range 5-300 Gy (99.8 % fitting). The thermoluminescent response improvement of the topaz/corundum composites is attributed to the corundum formed in situ during sintering. Fading rate studies of the composite with the best sintering treatment revealed a signal decrease of 4 % after 15 days, which remained constant for up to 30 days, and 8 % after 60 days. The kinetic parameters, kinetics order (b), activation energy (E), and frequency factor (s) determined using the glow peak shape method showed second-order kinetics. The topaz/corundum composite with the best TL response (975 °C, 0 min) presents an effective atomic number (Zeff) of 11.74. The detection of lower doses (mGy) and the linear response at higher doses (Gy) of beta 90Sr, together with the other thermoluminescent properties, suggest that the topaz/corundum composites sintered at 975° for 0 min dwell time may find application in radiotherapy, geological dating, and environmental dosimetry.

Exploring the construct validity of the social cognition and object relations scale in a clinical sample.

The Social Cognition and Object Relations Scale-Global rating method (SCORS-G; Stein, Hilsenroth, Slavin-Mulford, & Pinsker, 2011; Westen, 1995) measures the quality of object relations in narrative material. This study employed a multimethod approach to explore the structure and construct validity of the SCORS-G. The Thematic Apperception Test (TAT; Murray, 1943) was administered to 59 patients referred for psychological assessment at a large Northeastern U.S. hospital. The resulting 301 TAT narratives were rated using the SCORS-G method. The 8 SCORS variables were found to have high interrater reliability and good internal consistency. Principal components analysis revealed a 3-component solution with components tapping emotions/affect regulation in relationships, self-image, and aspects of cognition. Next, the construct validity of the SCORS-G components was explored using measures of intellectual and executive functioning, psychopathology, and normal personality. The 3 SCORS-G components showed unique and theoretically meaningful relationships across these broad and diverse psychological measures. This study demonstrates the value of using a standardized scoring method, like the SCORS-G, to reveal the rich and complex nature of narrative material.

Qualitative studies conducted alongside randomized controlled trials in oncology: A scoping review of use and rigour of reporting.

BACKGROUND: Randomized controlled trials (RCTs) are the gold standard for generating evidence to inform clinical oncology practice. Knowledge gained through qualitative research methodologies can be complementary to that gained through RCTs. How qualitative research has been combined with RCTs in oncology has not been previously characterized. OBJECTIVE: This scoping review was conducted to summarize how qualitative research associated with RCTs in the oncology setting has been conducted and examine the quality of reporting. ELIGIBILITY CRITERIA: Manuscripts reporting on qualitative research linked with RCTs in the cancer context that involved patients (both adult and pediatric) and/or informal caregiver (friends/family) were included. SOURCES OF EVIDENCE: Peer-reviewed manuscripts indexed in MEDLINE (OVID) and CINAHL, published in English between 2008 and January 2019. CHARTING METHODS: Formal scoping review methods were followed. A data extraction tool informed by the research questions as well as the COnsolidated criteria for REporting Qualitative research (COREQ) was utilized. Extraction was conducted independently by two authors, with disagreements resolved by a third. RESULTS: Fifty-four articles were included. Assessing information sharing, diet/exercise, and psychotherapeutic interventions were the most common focuses of the RCTs. The most common focus of the qualitative component was on gaining insight into the experience of receiving the intervention or participating in RCT procedures. How the intervention impacted the cancer experience was not a common focus of the qualitative components. Some reports provided insufficient information to understand how the qualitative components aligned with the RCT components. The results of the qualitative and RCT components were not integrated to draw meaningful conclusions about the efficacy of the intervention under study in most cases. Reports focusing on only qualitative methods had higher median (Mdn) reporting of COREQ items compared to reports that included both the qualitative and RCT components (Mdn = 18 vs. Mdn = 14, respectively; p <0.001). CONCLUSIONS: This review identified that qualitative research has been combined with RCTs in the cancer context in a number of ways, most commonly to understand the experience of receiving study interventions or participating in trial procedures. Exploring how interventions impact other aspects of the cancer experience is an approach that should be considered in future work. Formalized guidelines for the design and reporting of investigations that combine qualitative and RCT approaches in the cancer context are expected to be of value. TWEETABLE ABSTRACT: Combining qualitative research with randomized controlled trials in oncology: an impornt opportunity for discovery.

Regulation of the immune response. I. Reduction in ability of specific antibody to inhibit long-lasting IgG immunological priming after removal of the Fc fragment.

The ability of 7S and F(ab')(2) antibody fragments to suppress priming with low doses of antigen was compared. The 7S preparation was approximately 100-1000 times more potent than the F(ab')(2) preparation when the agglutinin titers of the two preparations were the same. The presence of any ability to suppress priming in the F(ab')(2) preparation may reflect an inherent capacity of the F(ab')(2) antibody or contamination with small amounts of 7S antibody. The difference between 7S and F(ab')(2) antibody in ability to suppress priming is attributed to the lack of the Fc portion on the F(ab')(2) antibody. The Fc portion may be needed to prevent rapid excretion of antibody from the body, to induce rapid phagocytosis of antigen-antibody complexes with consequent breakdown and elimination of antigen, or to inactivate or suppress the antigen-sensitive cells from reacting to antigenic determinants. More detailed studies will permit a better assessment of the importance of these three possible regulatory roles of the Fc portion of the immunoglobulin in the immune response.

Enrollment of patients to clinical trials in haematological cancer in New South Wales: current status, perceived barriers and opportunities for improvement.

BACKGROUND: Enrolment of cancer patients in clinical trials is associated with significant positive outcomes. There are, however, limited Australian data on enrolment of patients with haematological malignancies to clinical trials. AIM: The aim of this study is to document the number of patients with haematological malignancies enrolled on clinical trials in NSW, to establish the barriers to trial recruitment and to examine possible means by which clinical trials participation may be improved. METHODS: Quantitative data on clinical trial accrual were obtained from all sites participating in clinical trials in haematological malignancies in NSW from 2004 to 2007 and were compared with the cancer incidence data for that period. Qualitative data on barriers and strategies for improvement were gathered using semi-structured interviews with clinical trials professionals from throughout NSW. RESULTS: Between 2004 and 2007 there were significant increases in the number of active centres, clinical trials and trial participation, and by 2007, 10.5% of all eligible patients with haematological malignancies in NSW were enrolled in relevant clinical trials. Resource constraints were the greatest perceived barrier to participation, but the success of clinical trials is also challenged by difficulties associated with communication, ethics review, trial coordination, trial design and support for emerging centres. CONCLUSION: While participation in clinical trials in haematological cancer in NSW improved between 2004 and 2007, participation in clinical trials remains suboptimal. The development of specific strategies to address barriers to participation may facilitate increased enrolment and ultimately improve clinical outcomes in patients with haematological malignancies.

Generation of effective zinc-deficient agar-solidified media allows identification of root morphology changes in response to zinc limitation.

Earlier, we demonstrated that transcript levels of METAL TOLERANCE PROTEIN2 (MTP2) and of HEAVY METAL ATPase2 (HMA2) increase strongly in roots of Arabidopsis upon prolonged zinc (Zn) deficiency and respond to shoot physiological Zn status, and not to the local Zn status in roots. This provided evidence for shoot-to-root communication in the acclimation of plants to Zn deficiency. Zn-deficient soils limit both the yield and quality of agricultural crops and can result in clinically relevant nutritional Zn deficiency in human populations. Implementing Zn deficiency during cultivation of the model plant Arabidopsis thaliana on agar-solidified media is difficult because trace element contaminations are present in almost all commercially available agars. Here, we demonstrate root morphological acclimations to Zn deficiency on agar-solidified medium following the effective removal of contaminants. These advancements allow reproducible phenotyping toward understanding fundamental plant responses to deficiencies of Zn and other essential trace elements.

Regulation of acetylation of plant cell wall components is complex and responds to external stimuli.

Previously, we reported that the allelic de-etiolated by zinc (dez) and trichome birefringence (tbr) mutants exhibit photomorphogenic development in the dark, which is enhanced by high Zn. TRICHOME BIREFRINGENCE-LIKE proteins had been implicated in transferring acetyl groups to various hemicelluloses. Pectin O-acetylation levels were lower in dark-grown dez seedlings than in the wild type. We observed Zn-enhanced photomorphogenesis in the dark also in the reduced wall acetylation 2 (rwa2-3) mutant, which exhibits lowered O-acetylation levels of cell wall macromolecules including pectins and xyloglucans, supporting a role for cell wall macromolecule O-acetylation in the photomorphogenic phenotypes of rwa2-3 and dez. Application of very short oligogalacturonides (vsOGs) restored skotomorphogenesis in dark-grown dez and rwa2-3. Here we demonstrate that in dez, O-acetylation of non-pectin cell wall components, notably of xyloglucan, is enhanced. Our results highlight the complexity of cell wall homeostasis and indicate against an influence of xyloglucan O-acetylation on light-dependent seedling development.

A catalyst for transforming health systems and person-centred care: Canadian national position statement on patient-reported outcomes.

Background: Patient-reported outcomes (pros) are essential to capture the patient's perspective and to influence care. Although pros and pro measures are known to have many important benefits, they are not consistently being used and there is there no Canadian pros oversight. The Position Statement presented here is the first step toward supporting the implementation of pros in the Canadian health care setting. Methods: The Canadian pros National Steering Committee drafted position statements, which were submitted for stakeholder feedback before, during, and after the first National Canadian Patient Reported Outcomes (canpros) scientific conference, 14-15 November 2019 in Calgary, Alberta. In addition to the stakeholder feedback cycle, a patient advocate group submitted a section to capture the patient voice. Results: The canpros Position Statement is an outcome of the 2019 canpros scientific conference, with an oncology focus. The Position Statement is categorized into 6 sections covering 4 theme areas: Patient and Families, Health Policy, Clinical Implementation, and Research. The patient voice perfectly mirrors the recommendations that the experts reached by consensus and provides an overriding impetus for the use of pros in health care. Conclusions: Although our vision of pros transforming the health care system to be more patient-centred is still aspirational, the Position Statement presented here takes a first step toward providing recommendations in key areas to align Canadian efforts. The Position Statement is directed toward a health policy audience; future iterations will target other audiences, including researchers, clinicians, and patients. Our intent is that future versions will broaden the focus to include chronic diseases beyond cancer.

Early-life origins of disparities in chronic diseases among Indigenous youth: pathways to recovering health disparities from intergenerational trauma.

Indigenous women and children experience some of the most profound health disparities globally. These disparities are grounded in historical and contemporary trauma secondary to colonial atrocities perpetuated by settler society. The health disparities that exist for chronic diseases may have their origins in early-life exposures that Indigenous women and children face. Mechanistically, there is evidence that these adverse exposures epigenetically modify genes associated with cardiometabolic disease risk. Interventions designed to support a resilient pregnancy and first 1000 days of life should abrogate disparities in early-life socioeconomic status. Breastfeeding, prenatal care and early child education are key targets for governments and health care providers to start addressing current health disparities in cardiometabolic diseases among Indigenous youth. Programmes grounded in cultural safety and co-developed with communities have successfully reduced health disparities. More works of this kind are needed to reduce inequities in cardiometabolic diseases among Indigenous women and children worldwide.

Calcitonin gene-related peptide8-37 antagonizes capsaicin-induced vasodilation in the skin: evaluation of a human in vivo pharmacodynamic model.

The purpose of this study was to identify the mediators involved in capsaicin-induced vasodilation in the human skin and to evaluate a pharmacodynamic model for the early clinical evaluation of calcitonin gene-related peptide (CGRP) receptor antagonists. Dermal blood flow (DBF) response of the forearm skin to topically applied capsaicin was measured using laser Doppler perfusion imaging in 22 subjects. The effect of intra-arterially administered CGRP(8-37) (1200 ng . min(-1) . dl(-1) forearm), indomethacin (5 mug . min(-1) . dl(-1) forearm), and N(G)-monomethyl-l-arginine (l-NMMA; 0.2 mg . min(-1) dl(-1) forearm), and orally administered aprepitant (375 mg) on capsaicin-induced dermal vasodilation was assessed. Furthermore, the diurnal variation of the DBF response to capsaicin was studied. CGRP(8-37) inhibited the capsaicin-induced DBF increase: 217(145, 290)% in infused versus 370 (254, 486)% in the noninfused arm [mean (95% CI); p = 0.004]. In contrast, indomethacin, l-NMMA, aprepitant, and the time of assessment did not affect the DBF response to capsaicin. Thus, capsaicin-induced vasodilation in the human forearm skin is largely mediated by CGRP, but not by vasodilating prostaglandins, nitric oxide, or substance P. The response to capsaicin does not display a circadian rhythm. A pharmacodynamic model is proposed to evaluate CGRP receptor antagonists in humans in vivo.

Personality disorders and nonfatal unintentional injuries among US adults.

OBJECTIVE: To investigate the association between personality disorders and nonfatal unintentional injuries in a representative sample of US adults. METHODS: Data on self-reported nonfatal unintentional injuries during the 12 months before the interview were obtained from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were analyzed; 43,093 adults > or = 18 years participated in the NESARC wave I survey in 2001-02. Personality disorders were determined using the NIAAA Alcohol Use Disorders and Associated Disabilities Interview Schedule-DSM-IV. RESULTS: Individuals with at least one personality disorder had a significantly higher 12-month incidence of injuries than people without any personality disorder (p<0.001). After accounting for sociodemographic characteristics or other mental disorders, OR was 1.54 (95% CI 1.39 to 1.71) for individuals with one personality disorder and 1.80 (95% CI 1.58 to 2.05) for individuals with two or more personality disorders compared with people with no personality disorder. CONCLUSION: Personality disorders were associated with a significantly increased risk of unintentional injuries. This information has important implications for the treatment of patients with these disorders.

Unintentional pediatric submersion-injury-related hospitalizations in the United States, 2003.

The objective of this study was to examine the demographic characteristics and hospital resource utilization of submersion-injury-related hospitalizations among persons < or =20 years of age in the USA in 2003. All 1475 pediatric submersion-injury-related hospital discharges in the Kids' Inpatient Database were identified by ICD-9-CM diagnosis code or external cause of injury code. These cases represent an estimated 2490 pediatric submersion-injury-related hospitalizations nationwide. Inpatient costs for these estimated hospitalizations were approximately $10 million. The overall pediatric submersion-injury-related rate of hospitalization was 3.0 per 100,000 persons. Children aged 0-4 years had the highest rate of hospitalization (7.7 per 100,000 persons). Children with permanent submersion-injury-related morbidity accounted for 5.8% of hospital admissions and 37.3% of hospital costs in our study, and children with submersion-injury-related in-hospital death accounted for 11.6% of hospital admissions and 20.0% of hospital costs in our study. Prevention of submersion injury using focused, proven strategies deserves increased attention.

Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report.

The effect of PG on patients with fulminant and subfulminant viral hepatitis (FHF) was studied. 17 patients presented with FHF secondary to hepatitis A (n = 3), hepatitis B (n = 6), and non-A, non-B (NANB) hepatitis (n = 8). 14 of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation the mean aspartate transaminase (AST) was 1,844 +/- 1,246 U/liter, bilirubin 232 +/- 135 mumol/liter, prothrombin time (PT) 34 +/- 18, partial thromboplastin time (PTT) 73 +/- 26 s, and coagulation Factors V and VII 8 +/- 4 and 9 +/- 5%, respectively. Intravenous PGE1 was initiated 24-48 h later after a rise in AST (2,195 +/- 1,810), bilirubin (341 +/- 148), PT (36 +/- 15), and PTT (75 +/- 18). 12 of 17 responded rapidly with a decrease in AST from 1,540 +/- 833 to 188 +/- 324 U/liter. Improvement in hepatic synthetic function was indicated by a decrease in PT from 27 +/- 7 to 12 +/- 1 s and PTT from 61 +/- 10 to 31 +/- 2 s, and an increase in Factor V from 9 +/- 4 to 69 +/- 18% and Factor VII from 11 +/- 5 to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT, and improvement was observed upon retreatment. After 4 wk of intravenous therapy oral PGE2 was substituted. Two patients with NANB hepatitis recovered completely and remained in remission 6 and 12 mo after cessation of therapy. Two additional patients continued in remission after 2 and 6 mo of PGE2. No relapses were seen in the patients with hepatitis A virus and hepatitis B virus infection. Liver biopsies in all 12 surviving patients returned to normal. In the five nonresponders an improvement in hepatic function was indicated by a fall in AST (3,767 +/- 2,611 to 2,142 +/- 2,040 U/liter), PT (52 +/- 25 to 33 +/- 18 s), and PTT (103 +/- 29 to 77 +/- 44 s), but all deteriorated and died of cerebral edema (n = 3) or underwent liver transplantation (n = 2). These results suggest efficacy of PGE for FHF, and further investigation is warranted.

Portable 24-analyte surface plasmon resonance instruments for rapid, versatile biodetection.

Field use of surface plasmon resonance (SPR) biosensors for environmental and defense applications such as detection and identification of biological warfare agents has been hampered by lack of rugged, portable, high-performance instrumentation. To meet this need, we have developed compact multi-analyte SPR instruments based on Texas Instruments' Spreeta sensing chips. The instruments weigh 3 kg and are built into clamshell enclosures measuring 28 cm x 22 cm x 13 cm. Functions are divided between an electronics unit in the base of the box and a fluidics assembly in the lid. Automated valves and pumps implement an injection loop flow system that allows sensors to be exposed to sample, rinsed, and treated with additional reagents (such as secondary antibodies) under computer control. Injected samples flow over the surfaces of eight sensor chips fastened into a temperature-controlled silicone flowcell. Each chip has 3 sensing regions, for a total detection of 24 areas that can be simultaneously monitored by SPR. Coating these areas with appropriate antibodies or other receptors allows a sample to be screened for up to 24 different substances simultaneously. The instruments report refractive index (RI) values every second, with a typical noise level of 1-3 x 10(-6) RI units. The design of the device is described, and performance is illustrated with detection of six distinct analytes ranging from small molecules to whole microbes during the course of a single experiment.

Can we improve on situational judgement tests?

Situational judgement tests (SJTs) are multiple-choice psychological assessments that claim to measure professional attributes such as empathy, integrity, team involvement and resilience. One of their attractions is the ability to rank large numbers of candidates. Last year SJTs formed a major component (50% of the assessment marks) of the selection process for dental foundation training (DFT). However, it is not clear what SJTs are actually assessing. There is also the concern that applicants who have developed ethical reasoning skills may be disadvantaged by such tests. The DFT selection process needs to explicitly recognise the importance of ethical reasoning.

Neoadjuvant taxanes in the treatment of non-metastatic breast cancer: a systematic review.

In recent years the role of neoadjuvant (primary, preoperative) chemotherapy has undergone rapid progress. Initially, neoadjuvant chemotherapy use was limited to those patients with inoperable locally advanced breast cancer in an attempt to try to down-size the tumour to make effective surgery possible. The advent of more effective chemotherapy regimens has led to an increased use of neoadjuvant therapy to shrink potentially operable tumours to allow for breast conservation when a mastectomy would have been required previously. While neoadjuvant treatment for operable tumours has indeed allowed increased rates of breast conserving surgery, it has not yet demonstrated any survival benefit over standard postoperative anthracycline-based chemotherapy. Echoing the evolution of taxane based chemotherapy from the metastatic setting through to the adjuvant situation, there has been increased interest in the role of taxanes in neoadjuvant regimens. The use of taxane-based therapies in this setting has so far shown improvements over more standard regimens in terms of clinical response rates, breast conservation, pathologic response rates, disease free survival, and overall survival. The aim of this review is to systematically summarize and interpret the results of published randomized controlled trials of neoadjuvant taxane chemotherapy for women with non-metastatic breast cancer.