Radiotherapy for Oropharyngeal Carcinoma With an Uninvolved Contralateral Neck: The Safety of Omission of Contralateral High Level II and Retropharyngeal Lymph Nodes From Elective Target Volumes.

AIMS: To analyse outcomes and patterns of failure in patients with oropharyngeal carcinoma (OPC) treated with definitive volumetric modulated arc therapy with omission of contralateral high level II lymph nodes (HLII) and retropharyngeal lymph nodes (RPLN) in the contralateral uninvolved neck. MATERIALS AND METHODS: Patients with OPC treated between January 2016 and July 2019 were retrospectively identified. In the absence of contralateral neck disease, institutional protocols allowed omission of contralateral HLII and contralateral RPLN in the additional absence of ipsilateral RPLN, soft palate/posterior pharyngeal wall primary. RESULTS: In total, 238 patients with OPC and an uninvolved contralateral neck received definitive (chemo)radiotherapy with bilateral neck treatment. The median follow-up was 30.6 months. Two-year local control, regional control and overall survival were 91.0, 91.6 and 86.5%, respectively. Contralateral HLII were omitted in 159/238 (66.8%) patients; this included 106 patients in whom the primary tumour was at/crossed the midline. The contralateral RPLN region was omitted from elective target volumes for 175/238 (73.5%); this included 114 patients with a primary tumour at/crossed the midline. The mean contralateral parotid dose when contralateral HLII and RPLN were both omitted was 24.4 Gy, compared with 28.3 Gy without HLII/RPLN omission (P < 0.001). Regional progression occurred in 18/238 (7.6%) patients, all involving the ipsilateral neck with one bilateral. There were no recurrences in the contralateral HLII or RPLN regions. CONCLUSION: In patients with OPC and an uninvolved contralateral neck receiving bilateral (chemo)radiotherapy, the omission of contralateral RPLN and HLII from elective target volumes was safe and could lead to reduced contralateral parotid doses.

Quality Assurance Peer Review of Head and Neck Contours in a Large Cancer Centre via a Weekly Meeting Approach.

AIMS: To assess the impact of weekly scheduled peer review of head and neck contours for definitive and adjuvant radiotherapy cases based on rates of recommended changes. MATERIALS AND METHODS: Retrospective analysis of a prospective database. Recommended changes were prospectively classified as 'major' (change in gross tumour volume and/or high-dose clinical target volume, dose/fractionation) or 'minor' (change in intermediate or elective dose clinical target volumes or organs at risk). Univariate analysis to explore associations between recommended changes and tumour site/stage and radical/adjuvant indication. RESULTS: In total, 307/375 (82%) head and neck cases treated with volumetric-modulated arc therapy were prospectively peer reviewed over a 12-month period; 195 (64%) cases received definitive and 112 (36%) received adjuvant radiotherapy. Overall, 43/307 (14.0%) changes were recommended within the peer review meetings. This comprised 27/307 (8.8%) major changes and 16/307 (5.2%) minor changes; 33/43 (77%) changes were in the clinical target volume. Rates of recommended changes were significantly higher for adjuvant versus definitive radiotherapy (odds ratio 2.26, P = 0.014) and for larynx compared with oropharynx (odds ratio 3.02, P = 0.02). There was no overall correlation between clinician experience and rates of change (P = 0.62). CONCLUSION: Routine weekly meeting contour-based peer review resulted in a number of major and minor changes to treatment. Compliance was high. Peer review was potentially beneficial for all tumour sites/stages/indications and any degree of clinician experience.

Sex steroid hormones in relation to Barrett's esophagus: an analysis of the FINBAR Study.

Previously, we observed strong positive associations between circulating concentrations of free testosterone and free dihydrotestosterone (DHT) in relation to Barrett's esophagus in a US male military population. To replicate these findings, we conducted a second study of sex steroid hormones and Barrett's esophagus in the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study based in Northern Ireland and Ireland. We used mass spectrometry to quantitate EDTA plasma concentrations of nine sex steroid hormones and ELISA to quantitate sex hormone-binding globulin in 177 male Barrett's esophagus cases and 185 male general population controls within the FINBAR Study. Free testosterone, free DHT, and free estradiol were estimated using standard formulas. Multivariable logistic regression estimated odds ratios (OR) and 95% confidence intervals (95%CI) of associations between exposures and Barrett's esophagus. While plasma hormone and sex hormone-binding globulin concentrations were not associated with all cases of Barrett's esophagus, we did observe positive associations with estrogens in younger men (e.g. estrone + estradiol ORcontinuous per ½IQR  = 2.92, 95%CI:1.08, 7.89), and free androgens in men with higher waist-to-hip ratios (e.g. free testosterone ORcontinuous per ½IQR  = 2.71, 95%CI:1.06, 6.92). Stratification by body mass index, antireflux medications, and geographic location did not materially affect the results. This study found evidence for associations between circulating sex steroid hormones and Barrett's esophagus in younger men and men with higher waist-to-hip ratios. Further studies are necessary to elucidate whether sex steroid hormones are consistently associated with esophageal adenocarcinogenesis.

Heller's myotomy and pneumatic dilatation in the treatment of achalasia: a population-based case-control study assessing long-term quality of life.

Long-term health-related quality-of-life (HRQL) outcomes have not been widely reported in the treatment of achalasia. The aims of this study were to examine long-term disease-specific and general HRQL in achalasia patients using a population-based case-control method, and to assess HRQL between treatment interventions. Manometrically diagnosed achalasia cases (n = 120) were identified and matched with controls (n = 115) using a population-based approach. Participants completed general (SF-12) and disease-specific (Achalasia Severity Questionnaire [ASQ]) HRQL questionnaires, as appropriate, in a structured interview. Mean composite scores for SF-12 (Mental Component Summary score [MCS-12] and Physical Component Summary score [PCS-12]) and ASQ were compared between cases and controls, or between intervention groups, using an independent t-test. Adjusted mean differences in HRQL scores were evaluated using a linear regression model. Achalasia cases were treated with a Heller's myotomy (n = 43), pneumatic dilatation (n = 44), or both modalities (n = 33). The median time from last treatment to HRQL assessment was 5.7 years (interquartile range 2.4-11.5). Comparing achalasia patients with controls, PCS-12 was significantly worse (40.9 vs. 44.2, P = 0.01), but MCS-12 was similar. However, both PCS-12 (39.9 vs. 44.2, P = 0.03) and MCS-12 (46.7 vs. 53.5, P = 0.004) were significantly impaired in those requiring dual treatment compared with controls. Overall however, there was no difference in adjusted HRQL between patients treated with Heller's myotomy, pneumatic dilatation or both treatment modalities. In summary, despite treatment achalasia patients have significantly worse long-term physical HRQL compared with population controls. No HRQL differences were observed between the treatment modalities to suggest a benefit of one treatment over another.

The value of adjuvant radiotherapy on survival and recurrence in triple-negative breast cancer: A systematic review and meta-analysis of 5507 patients.

BACKGROUND: The value of adjuvant radiotherapy in triple negative breast cancer (TNBC) remains unclear. A systematic review and meta-analysis was conducted in TNBC patients to assess survival and recurrence outcomes associated with radiotherapy following either breast conserving therapy (BCT) or post-mastectomy radiotherapy (PMRT). METHODS: Four electronic databases were searched from January 2000 to November 2015 (PubMed, MEDLINE, EMBASE and Web of Science). Studies investigating overall survival and/or recurrence in TNBC patients according to radiotherapy administration were included. A random effects meta-analysis was conducted using mastectomy only patients as the reference. RESULTS: Twelve studies were included. The pooled hazard ratio (HR) for locoregional recurrence comparing BCT and PMRT to mastectomy only was 0.61 (95% confidence interval [CI] 0.41-0.90) and 0.62 (95% CI 0.44-0.86), respectively. Adjuvant radiotherapy was not significantly associated with distant recurrence. The pooled HR for overall survival comparing BCT and PMRT to mastectomy only was 0.57 (95% CI 0.36-0.88) and HR 1.12 (95% CI 0.75, 1.69). Comparing PMRT to mastectomy only, tests for interaction were not significant for stage (p=0.98) or age at diagnosis (p=0.85). However, overall survival was improved in patients with late-stage disease (T3-4, N2-3) pooled HR 0.53 (95% CI 0.32-0.86), and women <40years, pooled HR 0.30 (95% CI 0.11-0.82). CONCLUSIONS: Adjuvant radiotherapy was associated with a significantly lower risk of locoregional recurrence in TNBC patients, irrespective of the type of surgery. While radiotherapy was not consistently associated with an overall survival gain, benefits may be obtained in women with late-stage disease and younger patients.

Post-diagnostic oral bisphosphonate use and colorectal cancer mortality: a population-based cohort study within the UK Clinical Practice Research Datalink.

BACKGROUND: We conducted the first study to investigate post-diagnostic oral bisphosphonates use and colorectal cancer-specific mortality. METHODS: Colorectal cancer patients were identified from the National Cancer Data Repository (1998-2007) and linked to the UK Clinical Practice Research Datalink, providing prescription records, and Office of National Statistics mortality data. Time-dependent Cox regression models investigated colorectal cancer-specific mortality in post-diagnostic bisphosphonate users. RESULTS: Overall, in 4791 colorectal cancer patients, there was no evidence of an association between bisphosphonate use and colorectal cancer-specific mortality (adjusted hazard ratio=1.11; 95% confidence interval 0.80, 1.54) or with drug frequency or type. CONCLUSIONS: In this novel population-based cohort study, post-diagnostic bisphosphonate use was not associated with longer rates of colorectal cancer survival.

The effect of warfarin therapy on breast, colorectal, lung, and prostate cancer survival: a population-based cohort study using the Clinical Practice Research Datalink.

PURPOSE: Pre-clinical studies suggest that oral anticoagulant agents, such as warfarin, may inhibit metastases and potentially prolong survival in cancer patients. However, few population-based studies have examined the association between warfarin use and cancer-specific mortality. METHODS: Using prescribing, cause of death, and cancer registration data from the UK Clinical Practice Research Datalink, four population-based cohorts were constructed, comprising breast, colorectal, lung, and prostate cancer patients diagnosed between 1 January 1998, and the 31 December 2010. Comparing pre-diagnostic warfarin users to non-users, multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer-specific mortality. RESULTS: Overall, 16,525 breast, 12,902 colorectal, 12,296 lung, and 12,772 prostate cancers were included. Pre-diagnostic warfarin use ranged from 2.4 to 4.7 %. There was little evidence of any strong association between warfarin use pre-diagnosis and cancer-specific mortality in prostate (adjusted HR 1.03, 95 % CI 0.84-1.26), lung (adjusted HR 1.06, 95 % CI 0.96-1.16), breast (adjusted HR 0.81, 95 % CI 0.62-1.07), or colorectal (adjusted HR 0.88, 95 % CI 0.77-1.01) cancer patients. Dose-response analyses did not reveal consistent evidence of reductions in users of warfarin defined by the number of prescriptions used and daily defined doses. CONCLUSIONS: There was little evidence of associations between pre-diagnostic use of warfarin and cancer-specific mortality in lung, prostate, breast, or colorectal cancer patients.

Fruit and vegetable consumption and muscle strength and power during adolescence: a cross-sectional analysis of the Northern Ireland Young Hearts Project 1999-2001.

OBJECTIVES: To examine the association between fruit and vegetable (FV) consumption and muscle strength and power in an adolescent population. METHODS: We conducted a cross-sectional analysis among 1019 boys and 998 girls, aged 12 and 15 years, who participated in The Young Hearts Project. FV consumption (excluding potatoes) was assessed by 7-d diet history. Grip strength and jump power was assessed with a dynamometer and Jump-MD meter, respectively. Associations between FV consumption and strength and power were assessed by regression modelling. RESULTS: Boys and girls with the highest FV intakes (>237.71 g/d and >267.57 g/d, respectively, based on the highest tertile) had significantly higher jump power than those with the lowest intakes (<135.09 g/d and <147.43 g/d, respectively), after adjustment for confounding factors. Although girls with the highest FV intakes had higher grip strength than those with the lowest intakes, no significant independent associations were evident between FV intake and grip strength in boys or girls. Similar findings were observed when FV were analysed separately. CONCLUSIONS: Higher FV consumption in this group of adolescents was positively associated with muscle power. There was no independent association between higher FV consumption and muscle strength. Intervention studies are required to determine whether muscle strength and power can be improved through increased FV consumption.

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study.

BACKGROUND: Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. OBJECTIVES: To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. METHODS: Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. RESULTS: Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. CONCLUSIONS: Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study.

ß-Blocker usage and colorectal cancer mortality: a nested case-control study in the UK Clinical Practice Research Datalink cohort.

BACKGROUND: Epidemiological and laboratory studies suggest that ß-blockers may reduce cancer progression in various cancer sites. The aim of this study was to conduct the first epidemiological investigation of the effect of post-diagnostic ß-blocker usage on colorectal cancer-specific mortality in a large population-based colorectal cancer patient cohort. PATIENTS AND METHODS: A nested case-control analysis was conducted within a cohort of 4794 colorectal cancer patients diagnosed between 1998 and 2007. Patients were identified from the UK Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with a colorectal cancer- specific death (data from the Office of National Statistics death registration system) were matched to five controls. Conditional logistic regression was applied to calculate odds ratios (OR) and 95% confidence intervals (95% CIs) according to ß-blocker usage (data from GP-prescribing records). RESULTS: Post-diagnostic ß-blocker use was identified in 21.4% of 1559 colorectal cancer-specific deaths and 23.7% of their 7531 matched controls, with little evidence of an association (OR = 0.89 95% CI 0.78-1.02). Similar associations were found when analysing drug frequency, ß-blocker type or specific drugs such as propranolol. There was some evidence of a weak reduction in all-cause mortality in ß-blocker users (adjusted OR = 0.88; 95% CI 0.77-1.00; P = 0.04) which was in part due to the marked effect of atenolol on cardiovascular mortality (adjusted OR = 0.62; 95% CI 0.40-0.97; P = 0.04). CONCLUSIONS: In this novel, large UK population-based cohort of colorectal cancer patients, there was no evidence of an association between post-diagnostic ß-blocker use and colorectal cancer-specific mortality. CLINICAL TRIALS NUMBER: NCT00888797.

Non-steroidal anti-inflammatory drug use and cervical cancer risk: a case-control study using the Clinical Practice Research Datalink.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) have many anticarcinogenic properties via the inhibition of cyclooxygenase 2 (COX-2). Only one study, a cohort study examining risk of all cancers, investigated their role in cervical cancer with inconsistent findings between non-aspirin NSAIDs and aspirin. The aim of this study was to further investigate NSAID/aspirin use and cervical cancer risk. METHODS: Using the United Kingdom Clinical Practice Research Datalink, 724 women diagnosed with cervical cancer between 1 January, 1995 and December 2010 were compared to 3479 women (without cervical cancer) matched on year of birth and general practice. Conditional logistic regression analysis adjusted for smoking, sexually transmitted infections, HRT and contraceptive use, was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for cervical cancer risk among users of any oral NSAIDs, non-aspirin NSAIDs and aspirin, as assessed from primary care prescribing data. RESULTS: Excluding the year prior to diagnosis, there was no association in adjusted analyses between ever vs. never use of an NSAID (OR 0.92, 95% CI 0.77-1.09), non-aspirin NSAID (OR 0.95, 95% CI 0.80-1.13) or low-dose aspirin (OR 1.07, 0.80-1.44) and cervical cancer risk. In analysis of daily defined doses, there was no association with cervical cancer risk comparing the highest users to non-users of NSAIDs (OR 0.98, 95% CI 0.69-1.39) or non-aspirin NSAIDs (OR 1.00, 95% CI 0.70-1.43) or low-dose aspirin (OR 1.04, 95% CI 0.59-1.81). CONCLUSION: This large historical cohort study found no evidence of an association between non-aspirin NSAID or aspirin use and cervical cancer risk.

Non-steroidal anti-inflammatory drug use and brain tumour risk: a case-control study within the Clinical Practice Research Datalink.

PURPOSE: The aetiology of primary brain tumours is largely unknown; the role of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin use and glioma risk has been inconclusive, but few population-based studies with reliable prescribing data have been conducted, and the association with meningioma risk has yet to be assessed. METHODS: The UK Clinical Practice Research Datalink was used to assess the association between aspirin and non-aspirin NSAID use and primary brain tumour risk using a nested case-control study design. Conditional logistic regression analysis was performed on 5,052 brain tumour patients aged 16 years and over, diagnosed between 1987 and 2009 and 42,678 controls matched on year of birth, gender and general practice, adjusting for history of allergy and hormone replacement therapy use in the glioma and meningioma models, respectively. RESULTS: In conditional logistic regression analysis, excluding drug use in the year preceding the index date, there was no association with non-aspirin NSAID use (OR 0.96, 95 % CI 0.81-1.13) or glioma risk comparing the highest category of daily defined dose to non-users; however, non-aspirin NSAID use was positively associated with meningioma risk (OR 1.35, 95 % CI 1.06-1.71). No association was seen with high- or low-dose aspirin use irrespective of histology. CONCLUSIONS: This large nested case-control study finds no association between aspirin or non-aspirin NSAID use and risk of glioma but a slight increased risk with non-aspirin NSAIDs and meningioma.

Non-steroidal anti-inflammatory drug and aspirin use and the risk of head and neck cancer.

BACKGROUND: Evidence for non-steroidal anti-inflammatory drugs (NSAIDs) preventing head and neck cancer (HNC) is inconclusive; however, there is some suggestion that aspirin may exert a protective effect. METHODS: Using data from the United States National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we examined the association between aspirin and ibuprofen use and HNC. RESULTS: Regular aspirin use was associated with a significant 22% reduction in HNC risk. No association was observed with regular ibuprofen use. CONCLUSION: Aspirin may have potential as a chemopreventive agent for HNC, but further investigation is warranted.

Adiponectin multimers, body weight and markers of cardiovascular risk in adolescence: Northern Ireland Young Hearts Project.

BACKGROUND: Research examining the relationship between adiponectin (AN) isoforms, body weight and cardiovascular (CV) risk factors is limited, particularly in younger populations. OBJECTIVES: To investigate the inter-relationships between AN isoforms and CV risk factors, and their dependence on body weight status, in adolescents. DESIGN: Blood samples from 92 obese, 92 overweight and 92 normal weight age- and sex-matched adolescents were analysed for traditional cardiovascular disease (CVD) risk biomarkers and also total, high molecular weight (HMW), medium and low molecular weight (LMW) AN. RESULTS: A significant inverse association was observed between total and HMW AN and waist-hip ratio (P=0.015, P=0.006, respectively), triglycerides (P=0.003, P=0.003, respectively) and systolic blood pressure (P=0.012, P=0.024, respectively) and a significant positive association with high-density lipoprotein (P<0.001, P<0.001, respectively) in multi-adjusted analyses. There was no evidence of a relationship between multimeric AN and high-sensitivity C-reactive protein. There was also little evidence of a relationship between LMW AN and CVD risk factors. There was a strong, body mass index (BMI)-independent, association between AN, CVD biomarkers and the hypertriglyceridemic waist phenotype. CONCLUSION: Prominent, BMI-independent associations between total and HMW AN, but not LMW AN, and CVD risk factors were already evident in this young population. This research in adolescents supports the contention that AN subfractions may have different biological actions. These associations in apparently healthy adolescents suggest an important role for AN and its subfractions in the pathogenesis of metabolic syndrome traits and indicate that the potential for total or HMW AN to act as early universal biomarkers of CV risk warrants further study.

Non-steroidal anti-inflammatory drugs for the treatment of cancer cachexia: a systematic review.

BACKGROUND: Cancer cachexia is a devastating syndrome of advanced malignancy which negatively impacts on patients' morbidity, mortality and quality of life. Chronic inflammation is a key characteristic of cancer cachexia. Therefore, non-steroidal anti-inflammatory drugs (NSAIDs) may be able to break the cycle of cachexia. AIM: To systematically review the literature on the use of NSAIDs for the treatment of cachexia in advanced cancer patients. DESIGN: All titles retrieved through searching were downloaded to a reference management database, duplicates were removed and the remaining citations were checked for eligibility. Full copies of all eligible articles were obtained and reviewed. DATA SOURCES: Electronic searches (from inception up to 09/2011) included CINAHL, MEDLINE, EMBASE, and Web of Science. Reference lists from reviewed articles, trial registers and abstracts from relevant conferences were searched. Eligibility criteria were (a) Randomised Controlled Trial; (b) participants were adults with cancer with weight loss or a clinical diagnosis of cachexia; (c) administration of oral NSAIDs. RESULTS: Four studies were included. These studies provided some evidence of positive therapeutic effect on quality of life, performance status, inflammatory markers, weight gain and survival, but there was insufficient evidence demonstrated for their widespread use in practice. CONCLUSIONS: Insufficient studies have been performed to allow a conclusion to be formed with regard to the effectiveness of NSAIDs in the treatment of cachexia in advanced cancer. Major challenges in this patient cohort include the lack of uniformity of inclusion criteria across studies and the frailty of the patients recruited.

Do perinatal and early life exposures influence the risk of malignant melanoma? A Northern Ireland birth cohort analysis.

AIM: Intrauterine, early life and maternal exposures may have important consequences for cancer development in later life. The aim of this study was to examine perinatal and birth characteristics with respect to Cutaneous malignant melanoma (CMM) risk. METHODS: The Northern Ireland Child Health System database was used to examine gestational age adjusted birth weight, infant feeding practices, parental age and socioeconomic factors at birth in relation to CMM risk amongst 447,663 infants delivered between January 1971 and December 1986. Follow-up of histologically verified CMM cases was undertaken from the beginning of 1993 to 31st December 2007. Multivariable adjusted unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) of CMM risk. RESULTS: A total of 276 CMM cases and 440,336 controls contributed to the final analysis. In reference to normal (gestational age-adjusted) weight babies, those heaviest at birth were twice as likely to develop CMM OR 2.4 (95% CI 1.1-5.1). Inverse associations with CMM risk were observed with younger (<25 years) parental age at birth and both a higher birth order and greater household density OR 0.61 (95% CI 0.37-0.99) and OR 0.56 (95% CI 0.30-1.0) respectively. CONCLUSION: This large study of early onset melanoma supports a positive association with higher birth weight (imperatively gestational age adjusted) and CMM risk which may be related to factors which drive intrauterine foetal growth. Strong inverse associations observed with higher birth order and household density suggest that early-life immune modulation may confer protection; findings which warrant further investigation in prospective analyses.

Errors during the preparation of drug infusions: a randomized controlled trial.

BACKGROUND: We investigated the extent and frequency of dose errors and treatment delays made as a consequence of preparing drug infusions at the bedside, rather than using pre-filled syringes. METHODS: Forty-eight nurses with critical care experience volunteered to take part in this randomized, blinded, controlled study conducted in the simulation centre of an urban hospital. They assisted in the management of a simulated patient with septic shock. Vasopressor infusions were prepared either by diluting concentrated drugs from ampoules or were provided in syringes pre-filled beforehand by an intensive care unit resident. RESULTS: The time taken for the infusion to be started and the final concentration of the drugs were measured. We also measured the concentration of infusions prepared by a pharmacist and a pharmaceutical company. Nurses took 156 s to start infusions when using pre-filled syringes compared with 276 s when preparing them de novo, a mean delay of 106 s [95% confidence interval (CI) 73-140 s, P<0.0001]. One infusion prepared from ampoules contained one-fifth of the expected concentration of epinephrine; another contained none at all. Medication errors were 17.0 times less likely when pre-filled syringes were used (95% CI 5.2-55.5), and infusions prepared by pharmacy and industry were significantly more likely to contain the expected concentration (P<0.001 for norepinephrine and P=0.001 for epinephrine). CONCLUSIONS: Providing drug infusions in syringes pre-filled by pharmacists or pharmaceutical companies would reduce medication errors and treatment delays, and improve patient safety. However, this approach would have substantial financial implications for healthcare providers, especially in less developed countries.

Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis.

Human Papillomavirus (HPV) related oropharyngeal squamous cell carcinomas (OPSCCs) are reported to have improved prognosis and survival in comparison to other head and neck squamous cell cancers (HNSCCs). This systematic review and meta-analysis examines survival differences in HPV-positive HNSCC and OPSCC subtypes including tonsillar carcinoma in studies not previously investigated. Four electronic databases were searched from their inception till April 2011. A random effects meta-analysis was used to pool study estimates evaluating disease-specific (death from HNSCC), overall (all-cause mortality), progression-free and disease-free (recurrence free) survival outcomes in HPV-positive vs. HPV-negative HNSCCs. All statistical tests were two-sided. Forty-two studies were included. Patients with HPV-positive HNSCC had a 54% better overall survival compared to HPV-negative patients HR 0.46 (95% CI 0.37-0.57); the pooled HR for tonsillar cancer and OPSCC was 0.50 (95% CI 0.33-0.77) and HR 0.47 (95% CI 0.35-0.62) respectively. The pooled HR for disease specific survival was 0.28 (95% CI 0.19-0.40); similar effect sizes were found irrespective of the adjustment for confounders, HPV detection methods or study location. Both progression-free survival and disease-free survival were significantly improved in HPV-positive HNSCCs. HPV-positive HNSCCs and OPSCCs patients have a significantly lower disease specific mortality and are less likely to experience progression or recurrence of their cancer than HPV-negative patients; findings which have connotations for treatment selection in these patients.

Increased diagnosis and detection rates of carcinoma in situ of the breast.

The purpose of this study was to identify trends in the diagnosis of carcinoma in situ (CIS) of the breast in the United Kingdom (UK) and the Republic of Ireland (ROI) and to examine the impact of mammography. Data on cases of newly diagnosed CIS of the breast and mode of detection (screen detected or not) were obtained, where available, from regional cancer registries between 1990 and 2007. Age-standardised diagnosis rates for the UK and the ROI, and regional screen detected diagnosis rates were compared by calculating the annual percentage change (APC) over time. The APC of the diagnosis rate amongst women aged 50-64 years (original screening age group) showed a significant 5.9% increase in the UK (1990-2007) and 11.5% increase in the ROI (1994-2007). The rate of diagnosis (50-64 years) stabilized in the UK between 2005 and 2007 and was substantially higher than in other western populations with national screening programmes. The APC of the diagnosis rate amongst those aged 65-69 years showed a significant 12.4% increase in the UK (1990-2007) and 10.3% increase in the ROI (1994-2007). amongst women aged 50-74 years in the UK, approximately 4,300 cases of CIS (≈90% ductal carcinoma in situ) were diagnosed in 2007. Our analyses have shown that screen detected CIS contributed primarily to the increase in diagnosis of CIS of the breast. The high diagnosis rate of screen detected CIS of the breast underlines the need for further research into lesion and patient characteristics that are related to progression of CIS to invasive disease to better target treatment.