Accuracy, Precision, and Trending Ability of Electrical Cardiometry Cardiac Index versus Continuous Pulmonary Artery Thermodilution Method: A Prospective, Observational Study.

INTRODUCTION: Evaluation of accuracy, precision, and trending ability of cardiac index (CI) measurements using the Aesculon™ bioimpedance electrical cardiometry (Aesc) compared to the continuous pulmonary artery thermodilution catheter (PAC) technique before, during, and after cardiac surgery. METHODS: A prospective observational study with fifty patients with ASA 3-4. At six time points (T), measurements of CI simultaneously by continuous cardiac output pulmonary thermodilution and thoracic bioimpedance and standard hemodynamics were performed. Analysis was performed using Bland-Altman, four-quadrant plot, and polar plot methodology. RESULTS: CI obtained with pulmonary artery thermodilution and thoracic bioimpedance ranged from 1.00 to 6.75 L min-1 and 0.93 to 7.25 L min-1, respectively. Bland-Altman analysis showed a bias between CIBIO and CIPAC of 0.52 liters min-1 m-2, with LOA of [-2.2; 1.1] liters min-1 m-2. Percentage error between the two techniques was above 30% at every time point. Polar plot methodology and 4-quadrant analysis showed poor trending ability. Skin incision had no effect on the results. CONCLUSION: CI obtained by continuous PAC and CI obtained by Aesculon bioimpedance are not interchangeable in cardiac surgical patients. No effects of skin incision were found. International clinical trial registration number is ISRCTN26732484.

Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

BACKGROUND: Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. METHODS: The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. DISCUSSION: If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. TRIAL REGISTRATION: The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch randomized controlled multicentre trial (BOOG 2013-07).

BACKGROUND: Trials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013-07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy. DESIGN: This study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up. DISCUSSION: We hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival. TRIAL REGISTRATION: The BOOG 2013-07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682 .

Impact of same-day antibiotic susceptibility testing on time to appropriate antibiotic treatment of patients with bacteraemia: a randomised controlled trial.

Inadequate therapy in bloodstream infections is suggested to be associated with higher mortality. We evaluated the reduction in inappropriate antibiotic therapy using rapid identification and antibiotic susceptibility testing (FAST) compared to standard of care (SOC) testing in patients with bloodstream infections. The FAST method used polymerase chain reaction (PCR) for identification and to detect growth in the presence or absence of antibiotics after only 6 h. For SOC testing, the BD Phoenix system was used. Patients with blood cultures growing Staphylococcus, Streptococcus or Enterococcus species or Gram-negative rods were randomised for FAST or SOC tests. A total of 129 patients were randomised for FAST and 121 patients for the SOC group. At the time SOC results became available, 78 patients in the FAST group could have been switched to more appropriate therapy. Although FAST results were highly accurate (agreement with SOC was 94%), they were only implemented in a minority (16) of patients. However, significantly fewer patients in the FAST group used inappropriate therapy at the time of SOC results (p = 0.025). The time to results in the FAST group was reduced by 15.6 h (p < 0.001). In the patients switched after FAST, this was done after a mean of 42.3 h compared to 61.4 h in those switched after SOC tests (p < 0.001). In bacteraemic patients, FAST resulted in significantly more patients using appropriate antibiotic therapy at the time SOC results were available and 15.6 h earlier than SOC tests. However, the implementation of FAST results was not optimal and no benefit on clinical outcome was shown.

Pain prevalence and its determinants after spinal cord injury: a systematic review.

Pain prevalence studies are important as they illustrate the magnitude of pain problems in a certain patient population, such as patients living with a spinal cord injury (SCI). Strikingly, reported pain prevalence rates in SCI patients are found to vary greatly, while determinants for the differences between pain prevalence reports remain unclear. We here aim to identify determinants for the differences (heterogeneity) in pain prevalence reports through a systematic review of all SCI pain prevalence reporting studies. Literature search was done using Medline, Cumulative Index to Nursing and Allied Health Literature, ISI Web of Knowledge and Embase. Data abstraction was performed while blinded and was followed by meta-(regression)-analyses. We identified 82 studies. Study design-related determinants of SCI pain prevalence reports were pain definition strictness (mild, moderate or high), primary study goal (pain study or not), data source (retrospective or not), and in a limited number of cases response/attrition rates. While correcting for these items, population characteristics correlating with pain prevalence rates were both proportion of patients with a depression and average time after injury (positive correlations). Between-study heterogeneity may remain even after the identification/correction of above-mentioned causes of heterogeneity.Pain after SCI does seem to relate to the duration of the injury and depression, yet major causes of bias in reported pain prevalence are found to be related to the primary study goal (pain study or not), choice of pain definition and the use of retrospective data.

The effects of vagus nerve stimulation on tryptophan metabolites in children with intractable epilepsy.

BACKGROUND: The mechanism of action of vagus nerve stimulation (VNS) in intractable epilepsy is not entirely clarified. It is believed that VNS causes alterations in cytokines, which can lead to rebalancing the release of neurotoxic and neuroprotective tryptophan metabolites. We aimed to evaluate VNS effects on tryptophan metabolites and on epileptic seizures and investigated whether the antiepileptic effectiveness correlated with changes in tryptophan metabolism. METHODS: Forty-one children with intractable epilepsy were included in a randomized, active-controlled, double-blind study. After a baseline period of 12 weeks, all children underwent implantation of a vagus nerve stimulator and entered a blinded active-controlled phase of 20 weeks. Half of the children received high-output (therapeutic) stimulation (n=21), while the other half received low-output (active control) stimulation (n=20). Subsequently, all children received high-output stimulation for another 19 weeks (add-on phase). Tryptophan metabolites were assessed in plasma and cerebrospinal fluid (CSF) by use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared between high- and low-output groups and between the end of both study phases and baseline. Seizure frequency was recorded using seizure diaries. Mood was assessed using Profile of Mood States (POMS) questionnaires. RESULTS: Regarding tryptophan metabolites, anthranilic acid (AA) levels were significantly higher at the end of the add-on phase compared with baseline (p=0.002) and correlated significantly with improvement of mood (τ=-0.39, p=0.037) and seizure frequency reduction (τ=-0.33, p<0.01). No significant changes were found between high- and low-output groups regarding seizure frequency. CONCLUSION: Vagus nerve stimulation induces a consistent increase in AA, a neuroprotective and anticonvulsant tryptophan metabolite. Moreover, increased AA levels are associated with improvement in mood and reduction of seizure frequency.

The influence of neuropathology on brain inflammation in human and experimental temporal lobe epilepsy.

It is unclear to what extent neuropathological changes contribute to brain inflammation observed in temporal lobe epilepsy (TLE). Here, we compared cytokine levels between histopathologically-confirmed sclerotic hippocampi and histopathologically-confirmed normal hippocampi from TLE patients. We analyzed a similar cytokine panel in the hippocampi of amygdala-kindled rats and we evaluated neuropathological changes by immunohistochemistry. In TLE patients, cytokine levels were not significantly different between sclerotic and non-sclerotic hippocampi. Though kindling resulted in increased astrocyte activation, cytokine levels and microglia activation were unchanged. These results suggest that the chronic epileptic state in TLE can also occur in the absence of intracerebral inflammation. Highlights.

Comparison of two scoring systems for diagnosing levator ani muscle damage.

INTRODUCTION AND HYPOTHESIS: Levator defects are risk factors for pelvic organ prolapse (POP) and its recurrence. The most widely used scoring systems for severity of defects shown on magnetic resonance imaging (MRI) and perineal ultrasound (US) are not identical. The aim of this study was to investigate the differences between these classification systems with regard to levator defects on US and their clinical relevance for recurrence after prolapse surgery. METHODS: Women with previous cystocele repair underwent transperineal 3D US. Levator defects were graded according to the scoring system described with regard to MRI (DeLancey et al.) and perineal US (Dietz et al.). The results were compared using the weighted kappa and receiver operating characteristic (ROC) curves (SPSS version 20.0). RESULTS: We assessed 152 women. On US classification, more defects were categorized as highest grade compared with MRI classification [n = 64 (42 %) vs. n = 41 (28 %), p < 0.01]. The grades of levator defects on both scoring systems showed very good agreement, with a weighted kappa of 0.82 [95 % confidence interval (CI) 0.75-0.88). The predictive value of scoring systems for cystocele recurrence after prolapse surgery showed an area under the receiver operating curve (AUC) of 0.63 and 0.64, respectively. CONCLUSIONS: Comparison of the two scoring systems showed good agreement but was lowest for the highest-grade defects. There was no difference in predictive value between scoring systems for cystocele recurrence after prolapse surgery.

Transperineal ultrasound compared to evacuation proctography for diagnosing enteroceles and intussusceptions.

INTRODUCTION: This study concerns the level of agreement between transperineal ultrasound and evacuation proctography for diagnosing enteroceles and intussusceptions. METHOD: In a prospective observational study, 50 consecutive women who were planned to have an evacuation proctography underwent transperineal ultrasound too. Sensitivity, specificity, positive (PPV) and negative predictive value, as well as the positive and negative likelihood ratio of transperineal ultrasound were assessed in comparison to evacuation proctography. To determine the interobserver agreement of transperineal ultrasound, the quadratic weighted kappa was calculated. Furthermore, receiver operating characteristic curves were generated to show the diagnostic capability of transperineal ultrasound. RESULTS: For diagnosing intussusceptions (PPV 1.00), a positive finding on transperineal ultrasound was predictive of an abnormal evacuation proctography. Sensitivity of transperineal ultrasound was poor for intussusceptions (0.25). For diagnosing enteroceles, the positive likelihood ratio was 2.10 and the negative likelihood ratio, 0.85. There are many false-positive findings of enteroceles on ultrasonography (PPV 0.29). The interobserver agreement of the two ultrasonographers assessed as the quadratic weighted kappa of diagnosing enteroceles was 0.44 and that of diagnosing intussusceptions was 0.23. CONCLUSION: An intussusception on ultrasound is predictive of an abnormal evacuation proctography. For diagnosing enteroceles, the diagnostic quality of transperineal ultrasound was limited compared to evacuation proctography.

Pain relief and quality-of-life improvement after spinal cord stimulation in painful diabetic polyneuropathy: a pilot study.

BACKGROUND: Painful diabetic polyneuropathy (PDP) is associated with high pain scores and is difficult to treat. Therefore, spinal cord stimulation (SCS) has been suggested as second-line treatment. In this study, the feasibility and efficacy of SCS in PDP were investigated, as well as the predictive value of clinical sensory testing for the treatment outcome. METHODS: Fifteen patients with intractable PDP in the lower limbs were recruited. During lead implantation, the feasibility of achieving adequate paraesthesia coverage using one stimulation lead was investigated. If trial stimulation was successful, a definitive neurostimulator was implanted. Pain intensity was scored using an 11-point numeric rating scale and patients' global impression of change scale. Additionally, neuropathic pain characteristics, quality of life, sleep quality and mood were assessed. The predictive value of clinical sensory testing for the treatment outcome was analysed. RESULTS: Adequate paraesthesia coverage was achieved in 14 out of 15 patients. Clinically relevant pain relief was present in 11 patients after trial stimulation and 10 patients at 12 months. The quality of life was significantly increased at 2 weeks and 3 months in patients with successful SCS treatment. Several neuropathic pain characteristics and quality of sleep were improved at 2 weeks and 12 months. Preoperative clinical sensory testing did not differentiate between treatment responders from non-responders. CONCLUSIONS: SCS seems to be an efficacious and feasible treatment for intractable PDP. In this exploratory study, it was not possible to predict the treatment outcome using clinical sensory testing. These results justify performing a randomized clinical trial.

Psychosocial adjustment in a Dutch sample of children with cerebral palsy.

BACKGROUND: Over the last couple of years, there has been increasing interest for QoL in children with CP. Psychosocial adjustment in these children remains underrepresented in current literature. AIMS: To describe psychosocial adjustment in children with CP by means of the Psychosocial Adjustment and Role Skills Scale III (PARS-III), to describe the psychometric properties of this questionnaire, to identify a cut-off score for psychosocial maladjustment and to investigate the relationship between patient characteristics (i.e. predictive factors) and psychosocial adjustment. METHODS: The parents of 93 children with CP (59 boys, 34 girls; mean age 12.3 years, SD 3.8; 4-18; GMFCS 1: 28, GMFCS 2: 5, GMFCS 3: 19, GMFCS 4: 18, GMFCS 5: 23) completed the PARS-III and the Child Behavior Checklist (CBCL) concerning the psychosocial and behavioral functioning of their child. RESULTS: Cronbach's alpha-coefficient for the PARS-III was 0.89 indicating good internal consistency. High correlation with the CBCL was found. Confirmatory factor analysis confirmed the 6 domain structure of the PARS-III. Overall, children with CP achieved lower psychosocial adjustment scores compared to healthy children. A cut-off score (1 SD below the mean) of 78 was found. When predicting psychosocial maladjustment in children with CP, less gross motor function, hand function, communication skills and bilateral involvement of CP are the most important factors, but these can only explain 36% of variation in psychosocial adjustment. CONCLUSION: Using the by-proxy version of the PARS-III it was found that children with CP are reported to achieve lower psychosocial adjustment scores than healthy children.

[The costs and benefits of an integrated approach to dementia]. / De kosten en opbrengsten van een geïntegreerde aanpak bij dementie.

BACKGROUND: An integrated approach to dementia is generally recommended because no one discipline is adequately equipped it deal with the complex psychic, physical and social problems that are inherent in dementia. A multidisciplinary approach, however, leads inevitably to higher costs. It is not known what the cost/benefit ratio will be. AIM: To describe our research into the costs and benefits of an integrated approach to dementia involving the use of a diagnostic research centre for psycho-geriatrics and thereafter to compare our findings with the results of other studies of the costs and benefits of an integrated approach. METHOD: We performed a prospective and randomised efficiency study and we compared our findings with the results of other studies of the costs and benefits of an integrated approach. We reviewed recent literature. RESULTS: The DRC-PG was more effective than normal care as far as the patients' quality of life was concerned, but was not more expensive. It can therefore be regarded as a cost-effective facility for ambulatory patients with dementia. Three other studies provided additional empirical evidence of the success of a similar integrated approach in various sectors involved in the care of patients with dementia. CONCLUSION: An integrated approach with regard to the diagnosis, treatment and management of dementia produces favourable results. More research is needed into the efficacy and cost-effectiveness of integrated care programmes. This should result in improvements in the care and treatment of patients with dementia.

Can morphine still be considered to be the standard for treating chronic pain? A systematic review including pair-wise and network meta-analyses.

OBJECTIVE: For chronic pain treatment many health care authorities consider morphine to be the reference standard for strategic decisions in pain therapy. Although morphine's effectiveness is clear and its cost is low, it's unclear whether morphine should remain the first choice or reference treatment. RESEARCH DESIGN AND METHODS: We performed a systematic review to evaluate the evidence available to support the position of morphine as the reference standard for step III opioids based on efficacy and tolerability outcomes. RESULTS: The search yielded 5,675 titles and 56 studies were included. Considerable heterogeneity precluded pair-wise meta-analysis on change of pain intensity and no difference between morphine and other opioids were found for tolerability outcomes. The network meta-analysis showed no statistically significant difference in change of pain intensity between morphine and oxycodone, methadone and oxymorphone. Compared to morphine, patients using buprenorphine are more likely to discontinue treatment due to lack of effect (OR 2.32, 95% CI 1.37 to 3.95). Patients using methadone are more likely to discontinue due to adverse events (OR 3.09, 95% CI 1.14 to 8.36), whereas this risk is decreased for patients using fentanyl (OR 0.29, 95% CI 0.17 to 0.50) or buprenorphine (OR 0.30, 95% CI 0.16 to 0.53). The most important limitation of this review is that the included studies are heterogeneous with regard to study population and intervention, which may affect the pooled effect estimates. The main strength is that we only included parallel RCTs, the strongest design for intervention studies. CONCLUSIONS: The current evidence is moderate, both in respect to the number of directly comparative studies and in the quality of reporting of these studies. No clear superiority in efficacy and tolerability of morphine over other opioids was found in pair-wise and network analyses. Based on these results, a justification for the placement of morphine as the reference standard for the treatment of severe chronic pain cannot be supported.

Economic evaluation of four follow-up strategies after curative treatment for breast cancer: results of an RCT.

BACKGROUND: An economic evaluation was performed alongside a randomised controlled trial (ISRCTN 74071417) investigating the cost-effectiveness of nurse-led telephone follow-up instead of hospital visits, and of a short educational group programme (EGP) in the first year after breast cancer treatment. METHOD: This economic evaluation (n = 299) compared the one-year costs and the effects of four follow-up strategies: (1) hospital follow-up; (2) nurse-led telephone follow-up; (3) hospital follow-up plus EGP; and (4) nurse-led telephone follow-up plus EGP. Costs were measured using cost diaries and hospital registrations. Quality-adjusted life years (QALYs) were measured using the EQ-5D. Outcomes were expressed in incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves. RESULTS: Hospital follow-up plus EGP yielded most QALYs (0.776), but also incurred the highest mean annual costs (€4914). The ICER of this strategy versus the next best alternative, nurse-led telephone follow-up plus EGP (0.772 QALYs and €3971), amounted to €235.750/QALY. Hospital and telephone follow-up without EGP both incurred higher costs and less QALYs than telephone follow-up plus EGP and were judged inferior. Hospital follow-up plus EGP was not considered cost-effective, therefore, telephone follow-up plus EGP was the preferred strategy. The probability of telephone follow-up plus EGP being cost-effective ranged from 49% to 62% for different QALY threshold values. Secondary and sensitivity analyses showed that results were robust. CONCLUSION: Nurse-led telephone follow-up plus EGP seems an appropriate and cost-effective alternative to hospital follow-up for breast cancer patients during their first year after treatment.

Nurse-led telephone follow-up and an educational group programme after breast cancer treatment: results of a 2 × 2 randomised controlled trial.

OBJECTIVE: To investigate whether frequent hospital follow-up in the first year after breast cancer treatment might partly be replaced by nurse-led telephone follow-up without deteriorating health-related quality of life (HRQoL), and whether a short educational group programme (EGP) would enhance HRQoL. PATIENTS AND METHODS: A multicentre pragmatic randomised controlled trial (RCT) with a 2×2 factorial design was performed among 320 breast cancer patients who were treated with curative intent. Participants were randomised to follow-up care as usual (3-monthly outpatient clinic visits), nurse-led telephone follow-up, or the former strategies combined with an educational group programme. The primary outcome for both interventions was HRQoL, measured by EORTC QLQ-C30. Secondary outcomes were role and emotional functioning and feelings of control and anxiety. RESULTS: Data of 299 patients were available for evaluation. There was no significant difference in HRQoL between nurse-led telephone and hospital follow-up at 12 months after treatment (p = 0.42; 95% confidence interval (CI) for difference: -1.93-4.64) and neither between follow-up with or without EGP (p = 0.86; 95% CI for difference: -3.59-3.00). Furthermore, no differences between the intervention groups and their corresponding control groups were found in role and emotional functioning, and feelings of control and anxiety (all p-values > 0.05). CONCLUSION: Replacement of most hospital follow-up visits in the first year after breast cancer treatment by nurse-led telephone follow-up does not impede patient outcomes. Hence, nurse-led telephone follow-up seems an appropriate way to reduce clinic visits and represents an accepted alternative strategy. An EGP does not unequivocally affect positive HRQoL outcomes.

5% lidocaine-medicated plaster vs other relevant interventions and placebo for post-herpetic neuralgia (PHN): a systematic review.

Several pharmacological treatments are used to manage post-herpetic neuralgia (PHN). The use of topical analgesics, such as 5% lidocaine-medicated plaster (5% LMP), may be preferable to systemic treatments in that they are formulated to produce a local pain relieving effect with minimal systemic absorption. However, direct head-to-head comparisons are relatively few, and a rigorous assessment of the relative efficacy and safety of the various treatment options is lacking. The objective of this study was to compare 5% LMP for the relief of PHN with other relevant interventions and placebo. Six databases were searched up to May 2010. Quantitative methods for data synthesis were used, and a network meta-analysis was conducted. Twenty unique studies (32 publications) were included. Placebo-controlled studies showed 5% LMP to be effective in providing pain relief and reducing allodynia while adverse event rates were generally low. A comparison between 5% LMP and pregabalin indicated the non-inferiority of 5% LMP for pain reduction and showed greater improvement of quality of life for 5% LMP. Adverse events (AE) were significantly fewer with 5% LMP. In the network meta-analysis, only 5% LMP and gabapentin were associated with a greater change in pain from baseline than placebo [-15.50 (95% CI -18.85 to -12.16) and -7.56 (95% CI -12.52 to -2.59) respectively]. 5% LMP was shown to be more effective than capsaicin [-16.45 (95% CI -20.04 to -12.86)], gabapentin [-7.95 (95% CI -13.29 to -2.61)] and pregabalin [-13.45 (95% CI -19.19 to -7.71)]. For pain relief, two comparators were more effective than placebo [mean pain relief, gabapentin: 32.77 (95% CI 15.57-49.97); 5% LMP: 26.77 (95% CI 9.11-44.43)]. 5% LMP was shown to be comparable to gabapentin [-6.00 (95% CI -25.32-13.32)]. The results suggest that 5% LMP and gabapentin have similar effects on pain relief and that 5% LMP is more effective than capsaicin and pregabalin (change in pain from baseline). Topical agents, such as 5% LMP, are associated with fewer and less clinically significant AE than is the case for systemic agents. However, small numbers, and limited size and quality of included studies should be taken into account. Further studies are needed.

A patient-centred instrument for assessment of quality of breast cancer care: results of a pilot questionnaire.

BACKGROUND: In several breast cancer research environments, there was a need to develop a questionnaire that would (1) provide data on how breast cancer patients experience healthcare services, (2) address issues corresponding with patients' needs and expectations and (3) produce useful data for quality assessment and improvement projects aimed at breast cancer care. This article describes the first part of the quantitative process of item selection, instrument construction and optimisation based on the results of a pilot questionnaire. METHODS: Based on qualitative research, a pilot questionnaire with items formulated as "performance" and "importance" statements was developed and sent to all breast cancer patients operated on in the previous 3-15 months in five participating hospitals. Reduction criteria, exploratory factor analysis and reliability analysis were used as part of the process of instrument optimisation. RESULTS: Of the 637 questionnaires sent out, 299 (47%) were returned and 276 (43%) were used for analyses. Out of the 72 quality items included in the pilot questionnaire, 42 items did not meet the inclusion criteria for the revised version. The remaining items refer to the factors patient education regarding aspects related to postoperative treatment, services by the breast nurse, services by the surgeon, patient education regarding activities at home and patient education regarding aspects related to preoperative treatment (Cronbach α = 0.70-0.89). CONCLUSIONS: In this study, the number of items to be included in the self-administered questionnaire was reduced. The resulting set of items that determines patients' perceptions on quality of breast cancer care is easy to complete and enables anonymous responses. Further research can be aimed at establishing the reliability of the current questionnaire.

Association between guideline adherence and clinical outcome for patients referred for diagnostic breast imaging.

OBJECTIVE: To assess the adherence to a guideline for additional breast ultrasonography in a cross-sectional survey among hospitals in The Netherlands. Furthermore, consequences of current practice non-adherence for the patient outcome of diagnostic breast imaging were studied. METHODS: Current practice was compared with a guideline made up of three recommendations for the use of ultrasonography after mammography and three recommendations for not using ultrasonography. All patients referred for mammography to the radiology departments of the participating hospitals during 2 months in 2004 were eligible for the study. No data on the gold standard for breast cancer were analysed, but clinical consequences were estimated by using a probability model based on the data of a former prospective clinical study. RESULTS: In total, 17 of the 66 hospitals approached were participating in the study. Of the 13,694 patients assessed for eligibility, 6457 were included. High adherence rates (81-97%, mean 94%) were observed for the recommendations, which indicate additional ultrasonography, whereas lower adherence rates (68-94%, mean 83%) were seen for the recommendations which do not advise additional ultrasonography. Overall, in all included hospitals, non-adherence would result in 27.2 false-positive and 1.1 false-negative imaging results. CONCLUSION: Current daily practice of diagnostic breast imaging in the hospitals in this survey corresponds to a great extent to the guideline proposed. Non-adherence in current practice results in a relatively small number of false-positive and false-negative imaging results.

Systematic review of aromatase inhibitors in the first-line treatment for hormone sensitive advanced or metastatic breast cancer.

To undertake a systematic review of three first-line treatments (letrozole, anastrozole and exemestane) for hormone sensitive advanced or metastatic breast cancer (MBC) in post-menopausal women. We searched six databases from inception up to January 2009 for relevant trials regardless of language or publication status. Randomised controlled clinical trials assessing the safety and efficacy of first-line AIs for post-menopausal women with hormone receptor-positive (HR+, i.e. ER+ and/or PgR+) with or without ErbB2 (HER2)-positive MBC, who have not received prior therapy for advanced or metastatic disease were included. Where meta-analysis using direct or indirect comparisons was considered unsuitable for some or all of the data, we employed a narrative synthesis method. Four studies (25 papers) met the inclusion criteria. From the available evidence, it was possible to directly compare the three AIs with tamoxifen. In addition, by using a network meta-analysis it was possible to compare the three AIs with each other. Based on direct evidence, letrozole seemed to be significantly better than tamoxifen in terms of time-to-progression (TTP) (HR = 0.70 (95% CI: 0.60, 0.82)), objective response rate (RR = 0.65 (95% CI: 0.52, 0.82)) and quality-adjusted time without symptoms or toxicity (Q-Twist difference = 1.5; P < 0.001). Exemestane seemed significantly superior to tamoxifen in terms of objective response rate (RR = 0.68 (95% CI: 0.53, 0.89)). Anastrozole seemed significantly superior to tamoxifen in terms of TTP in one trial (HR = 1.42 (95% CI: 1.15, NR)), but not in the other (HR = 1.01 (95% CI: 0.87, NR)). In terms of adverse events, no significant differences were found between letrozole and tamoxifen. Tamoxifen was associated with significantly more serious adverse events in comparison with exemestane (OR = 0.61 (95% CI: 0.38, 0.97)); while exemestane was associated with significantly more arthralgia in comparison with tamoxifen (OR = 2.33 (95% CI: 1.07, 5.11)). Anastrozole was associated with significantly more total adverse events (OR = 1.04 (95% CI: 1.00, 1.09)) and hot flushes (OR = 1.39 (95% CI: 1.03, 1.89)) in comparison with tamoxifen in one trial; however, the other trial showed no significant differences in adverse events between anastrozole and tamoxifen. The indirect comparison of AIs with each other in women with post-menopausal, hormone sensitive advanced or MBC showed that letrozole and exemestane were better in terms of objective response rate than anastrozole; while the more clinically relevant outcomes overall survival (OS) and progression-free survival (PFS) showed no significant differences between AIs. OS and PFS showed no significant differences between AIs and hence based on these results a class effect for all AIs is possible. However, these results are based on indirect comparisons and a network analysis for which the basic assumptions of homogeneity, similarity and consistency were not fulfilled. Therefore, despite the fact that these are the best available data, the results need to be interpreted with appropriate caution. Head-to-head comparisons between letrozole, anastrozole and exemestane in the first-line MBC setting are warranted.