Emotional and informational social support from health visitors and breastfeeding outcomes in the UK.

BACKGROUND: Shorter breastfeeding duration is associated with detrimental consequences for infant health/development and maternal health. Previous studies suggest social support is essential in maintaining breast/chest-feeding and helping to improve general infant feeding experiences. Public health bodies therefore work to support breastfeeding in the UK, yet UK breastfeeding rates continue to be one of the lowest globally. With this, a better understanding of the effectiveness and quality of infant feeding support is required. In the UK, health visitors (community public health nurses specialising in working with families with a child aged 0-5 years) have been positioned as one of the key providers of breast/chest-feeding support. Research evidence suggests that both inadequate informational support and poor/negative emotional support can lead to poor breastfeeding experiences and early breastfeeding cessation. Thus, this study tests the hypothesis that emotional support from health visitors moderates the relationship between informational support and breastfeeding duration/infant feeding experience among UK mothers. METHODS: We ran cox and binary logistic regression models on data from 565 UK mothers, collected as part of a 2017-2018 retrospective online survey on social support and infant feeding. RESULTS: Informational support, compared to emotional support, was a less important predictor of both breastfeeding duration and experience. Supportive emotional support with unhelpful or absent informational support was associated with the lowest hazard of breastfeeding cessation before 3 months. Results for breastfeeding experience followed similar trends, where positive experience was associated with supportive emotional and unhelpful informational support. Negative experiences were less consistent; however, a higher probability of negative experience was found when both types of support were reported as unsupportive. CONCLUSIONS: Our findings point to the importance of health visitors providing emotional support to bolster the continuation of breastfeeding and encourage a positive subjective experience of infant feeding. The emphasis of emotional support in our results encourages increased allocation of resources and training opportunities to ensure health visitors are able to provide enhanced emotional support. Lowering health visitors caseloads to allow for personalised care is just one actionable example that may improve breastfeeding outcomes in the UK.

Factors associated with advanced colorectal cancer differ between young and older adults in England: a population-based cohort study.

AIM: Advanced stage presentation of colorectal cancer is associated with poorer survival outcomes, particularly among young adults. This study aimed to determine whether demographic risk factors for advanced stage presentation differed between young and older adults. METHOD: Individual-level data on all incident colorectal cancers in people aged 20 years and above were extracted from the National Cancer Registration and Analysis Service database for the years 2012 to 2015. Patients were divided into two cohorts: young-onset colorectal cancer (YOCC) if aged 20-49 years and older-onset colorectal cancer (OOCC) if aged 50 years and above. Logistic regression was used to identify risk factors for advanced stage presentation, defined as TNM Stage III or IV, in each cohort. RESULTS: There were 7075 (5.2%) patients in the YOCC cohort and 128 345 (94.8%) patients in the OOCC cohort. Tumours in the YOCC cohort were more likely to be at an advanced stage (67.2% vs 55.3%, P < 0.001) and located distally (63.7% vs 55.4%, P < 0.001). No demographic factor was consistently associated with advanced stage presentation in the YOCC cohort. Among the OOCC cohort, increased social deprivation [OR (Index of Multiple Deprivation quintile 5 vs 1) = 1.11 (95% CI 1.07-1.16), P < 0.001], Black/Black British ethnicity [OR (baseline White) = 1.25 (95% CI 1.11-1.40), P < 0.001] and residence in the East Midlands [OR (baseline London) = 1.11 (95% CI 1.04-1.17), P = 0.001] were associated with advanced stage presentation. CONCLUSION: Demographic factors associated with advanced disease were influenced by age. The effects of social deprivation and ethnicity were only observed in older adults and mirror trends in screening uptake. Targeted interventions for high-risk groups are warranted.

Pneumomediastinum following intubation in COVID-19 patients: a case series.

The number of patients requiring tracheal intubation rose dramatically in March and April 2020 with the COVID-19 outbreak. Our thoracic surgery department has seen an increased incidence of severe pneumomediastinum referred for surgical opinion in intubated patients with COVID-19 pneumonitis. Here we present a series of five patients with severe pneumomediastinum requiring decompression therapy over a 7-day period in the current COVID-19 outbreak. We hypothesise that the mechanism for this is the aggressive disease pathophysiology with an increased risk of alveolar damage and tracheobronchial injury, along with the use of larger-bore tracheal tubes and higher ventilation pressures. We present this case series in order to highlight the increased risk of this potentially life-threatening complication among the COVID-19 patient cohort and offer guidance for its management to critical care physicians.

Demographic trends in the incidence of young-onset colorectal cancer: a population-based study.

BACKGROUND: Evidence is emerging that the incidence of colorectal cancer is increasing in young adults, but the descriptive epidemiology required to better understand these trends is currently lacking. METHODS: A population-based cohort study was carried out including all adults aged 20-49 years diagnosed with colorectal cancer in England between 1974 and 2015. Data were extracted from the National Cancer Registration and Analysis Service database using ICD-9/10 codes for colorectal cancer. Temporal trends in age-specific incidence rates according to sex, anatomical subsite, index of multiple deprivation quintile and geographical region were analysed using Joinpoint regression. RESULTS: A total of 56 134 new diagnoses of colorectal cancer were analysed. The most sustained increase in incidence rate was in the group aged 20-29 years, which was mainly driven by a rise in distal tumours. The magnitude of incident rate increases was similar in both sexes and across Index of Multiple Deprivation quintiles, although the most pronounced increases in incidence occurred in the southern regions of England. CONCLUSION: Colorectal cancer should no longer be considered a disease of older people. Changes in incidence rates should be used to inform future screening policy, preventative strategies and research agendas, as well as increasing public understanding that younger people need to be aware of the symptoms of colorectal cancer.

ANTECEDENTES: Están apareciendo evidencias de que la incidencia del cáncer colorrectal (colorectal cancer, CRC) está aumentando en adultos jóvenes, pero se carece de la epidemiología descriptiva necesaria para comprender mejor estas tendencias. MÉTODOS: Se realizó un estudio de cohortes de base poblacional de todos los adultos de 20 a 49 años diagnosticados de CRC en Inglaterra entre 1974 y 2015. Los datos se extrajeron de la base de datos NCRAS utilizando los códigos ICD9/10 para el CRC. Las tendencias temporales en las tasas de incidencia específicas por edad (incidence rates, IR) según el sexo, la localización anatómica, el quintil del índice de privación múltiple (index of multiple deprivation, IMD) y la región geográfica se analizaron mediante un modelo de regresión joinpoint. RESULTADOS: Se analizaron un total de 56.134 nuevos diagnósticos de CRC. El aumento más sostenido en la IR se produjo en el grupo de edad de 20 a 29 años, principalmente a expensas de un incremento de los tumores distales. La magnitud de los aumentos de IR fue similar en ambos sexos y en los quintiles del IMD, aunque los aumentos más pronunciados en la incidencia se registraron en las regiones del sur de Inglaterra. CONCLUSIÓN: El CRC ya no debe ser considerado una enfermedad de las personas mayores: los cambios en las tasas de incidencia deberán tenerse en cuenta en las futuras políticas de cribado, en las estrategias preventivas y en los proyectos de investigación, así como para aumentar la toma de conciencia de la población de que las personas más jóvenes deben estar al corriente de los síntomas del CRC.

Conditional approval of cancer drugs in Canada: accountability and impact on public funding.

Background: We examined how conditional market approval of cancer pharmaceuticals by Health Canada (hc) affects public funding recommendations by the pan-Canadian Oncology Review (pcodr). We were also interested to see how often hc conditions are enforced. Methods: Health Canada and pcodr databases for 2010-2017 were analyzed for patterns in hc conditional authorization and post-authorization reviews of cancer drugs and for correlation with pcodr reimbursement recommendations. Results: Between 2010 and 2017, pcodr reviewed 105 unique drug-indication pairings; 21% (n = 22) had conditional hc authorization. In all cases, conditional authorization was given on the basis of preliminary data in a surrogate endpoint and was contingent on further data showing benefit in more robust outcome measures (for example, overall survival). Of those 22 drugs, 36% did not have updated data, 36% had updated data that met hc conditions, and 27% had data that met some, but not all, conditions. During the period considered, hc never revoked conditional authorization for failure to meet conditions. None of the 22 drugs was given an unconditional positive recommendation for public reimbursement by pcodr. A conditional recommendation was given to 11 of the drugs (50%), and reimbursement was not recommended for 6 drugs (27%) because of insufficient evidence. Conclusions: One fifth of the cancer drugs reviewed for public reimbursement in Canada were conditionally authorized by hc based on preliminary data. Conditional authorization was associated with a recommendation against public funding by pcodr. No drugs had their conditional market authorization revoked for failure to meet conditions, suggesting that a more robust hc reappraisal framework is needed.

Optimized delivery of siRNA into 3D tumor spheroid cultures in situ.

3D tissue culture provides a physiologically relevant and genetically tractable system for studying normal and malignant human tissues. Despite this, gene-silencing studies using siRNA has proved difficult. In this study, we have identified a cause for why traditional siRNA transfection techniques are ineffective in eliciting gene silencing in situ within 3D cultures and proposed a simple method for significantly enhancing siRNA entry into spheroids/organoids. In 2D cell culture, the efficiency of gene silencing is significantly reduced when siRNA complexes are prepared in the presence of serum. Surprisingly, in both 3D tumour spheroids and primary murine organoids, the presence of serum during siRNA preparation rapidly promotes entry and internalization of Cy3-labelled siRNA in under 2 hours. Conversely, siRNA prepared in traditional low-serum transfection media fails to gain matrigel or spheroid/organoid entry. Direct measurement of CTNNB1 mRNA (encoding ß-catenin) from transfected tumour spheroids confirmed a transient but significant knockdown of ß-catenin when siRNA:liposome complexes were formed with serum, but not when prepared in the presence of reduced-serum media (Opti-MEM). Our studies suggest a simple modification to standard lipid-based transfection protocols facilitates rapid siRNA entry and transient gene repression, providing a platform for researchers to improve siRNA efficiency in established 3D cultures.

Outcomes of severe sepsis and septic shock patients after stratification by initial lactate value / 世界急诊医学杂志（英文）

BACKGROUND: In the setting of severe sepsis and septic shock, mortality increases when lactate levels are ≥ 4 mmol/L. However, the consequences of lower lactate levels in this population are not wel understood. The study aimed to determine the in-hospital mortality associated with severe sepsis and septic shock when initial lactate levels are < 4 mmol/L. METHODS: This is a retrospective cohort study of septic patients admitted over a 40-month period. Totally 338 patients were divided into three groups based on initial lactate values. Group 1 had lactate levels < 2 mmol/L; group 2: 2–4 mmol/L; and group 3: ≥ 4 mmol/L. The primary outcome was in-hospital mortality. RESULTS: There were 111 patients in group 1, 96 patients in group 2, and 131 in group 3. The mortality rates were 21.6％, 35.4％, and 51.9％ respectively. Univariate analysis revealed the mortality differences to be statistically significant. Multivariate logistic regression demonstrated higher odds of death with higher lactate tier group, however the findings did not reach statistical significance. CONCLUSION: This study found that only assignment to group 3, initial lactic acid level of ≥ 4 mmol/L, was independently associated with increased mortality after correcting for underlying severity of illness and organ dysfunction. However, rising lactate levels in the other two groups were associated with increased severity of illness and were inversely proportional to prognosis.

Nucleon Structure Functions from Operator Product Expansion on the Lattice.

Deep-inelastic scattering, in the laboratory and on the lattice, is most instructive for understanding how the nucleon is built from quarks and gluons. The long-term goal is to compute the associated structure functions from first principles. So far this has been limited to model calculations. In this Letter we propose a new method to compute the structure functions directly from the virtual, all-encompassing Compton amplitude, utilizing the operator product expansion. This overcomes issues of renormalization and operator mixing, which so far have hindered lattice calculations of power corrections and higher moments.

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy.

BACKGROUND: Complete tumour response (pCR) to neo-adjuvant chemo-radiotherapy for rectal cancer is associated with a reduction in local recurrence and improved disease-free and overall survival, but is achieved in only 20-30% of patients. Drug repurposing for anti-cancer treatments is gaining momentum, but the potential of such drugs as adjuncts, to increase tumour response to chemo-radiotherapy in rectal cancer, is only just beginning to be recognised. METHODS: A systematic literature search was conducted and all studies investigating the use of drugs to enhance response to neo-adjuvant radiation in rectal cancer were included. 2137 studies were identified and following review 12 studies were extracted for full text review, 9 studies were included in the final analysis. RESULTS: The use of statins or aspirin during neo-adjuvant therapy was associated with a significantly higher rate of tumour downstaging. Statins were identified as a significant predictor of pCR and aspirin users had a greater 5-year progression-free survival and overall survival. Metformin use was associated with a significantly higher overall and disease-free survival, in a subset of diabetic patients. CONCLUSIONS: Aspirin, metformin and statins are associated with increased downstaging of rectal tumours and thus may have a role as adjuncts to neoadjuvant treatment, highlighting a clear need for prospective randomised controlled trials to determine their true impact on tumour response and overall survival.

Peroxy Pyruvic Acid-Containing Topical Anti-Infective: A Potential Candidate for a Wound Instillation Solution.

Objective: Evaluate the therapeutic properties of a peroxy pyruvic acid (PPA)-containing topical anti-infective in a human ex-vivo model that replicates the natural conditions of a human chronic wound. Approach: Wound material was extracted from patients with nonhealing diabetic ulcers, venous stasis ulcers, and arterial wounds. Microbial species were identified, and wound colonization was quantified. Extracted samples were then exposed to a PPA-containing topical anti-infective as an instillation solution with negative pressure wound therapy NPWT at concentrations of 1,000, 1,500, or 2,500 ppm for a period of 1, 5, or 10 min to determine the effect of exposure on isolated pathogens, including effect on proteins. Results: A total of 32 samples were collected from patients. Samples presented with a range of bacteria and fungi representing 14 genera and 22 species, many of which are or are evolving to be resistant to many, if not most, current systemic antibiotics. Thirteen of twenty-three samples (57%) from chronic wounds had bacteria counts ≥105 and most were 6 logs or more. Seven of 10 samples (70%) from acute wounds had bacteria counts ≤105 and most were much lower. Exposure to PPA-containing topical anti-infective at 1,000 ppm killed all bacteria and fungi in all samples within 1 min of exposure. Innovation: PPA-containing topical anti-infective is a potentially valuable clinical option for NPWT. Conclusion: PPA-containing topical anti-infective is a potential candidate for use as an NPWT instillation solution for the treatment of wound infections caused by susceptible pathogens.

Effects of slip severity on muscle activation of the trailing leg during an unexpected slip.

Falls and injuries due to falls are a major health concern, and accidental slips are a leading cause of falls during gait. Understanding how the body reacts to an unexpected slip can aid in developing intervention techniques to reduce the number of injuries due to falls. In this study, muscle activation patterns, specifically those of the trailing (non-slipping) limb, were studied in unexpected slips of 24 young and 24 middle-aged adults. The typical reaction of the trailing limb is swing phase interruption in an attempt to arrest the slip. Variables examined were the reactive muscle activation onset, peak electromyography (EMG) magnitude, and time-to-peak of the vastus lateralis and medial hamstring of the trailing limb. Statistical analysis was performed to determine the effects of slip severity, quantified by peak slip velocity, and age on outcome variables. As slip severity increased, the reactive activation onset of the medial hamstring was significantly faster and there was a trend approaching significance for the onset of the vastus lateralis. Additionally, the peak magnitude and time-to-peak of the vastus lateralis increased with slip severity. No significant effects of age were found on any of the output variables. These findings may aid in development of perturbation-based paradigms, as it may be possible to "tune" the postural control system to generate an appropriate response to unexpected slips.

Improving postoperative pain management in subpectoral tissue expander implant reconstruction of the breast using an elastomeric pump.

INTRODUCTION: Postoperative pain after breast surgery is one of the major factors contributing to delay in mobilisation and prolonged hospital stay. A retrospective analysis was performed of patients undergoing skin sparing mastectomy and insertion of a subpectoral implant. The aim was to determine whether the use of an elastomeric local anaesthetic pump improved pain control and length of stay. METHODS: Twenty-five consecutive patients undergoing the above procedure were sited with an elastomeric local anaesthetic infusion pump intraoperatively, in addition to standard regular and pro re nata analgesia. The control group comprised 25 patients undergoing the same procedure in the same year who received standard analgesia alone. Visual analogue scale scores were recorded for the duration of inpatient stay, as was any further analgesic requirement. RESULTS: The median age was 51 years (range: 26-75 years) in the intervention group and 50 years (range: 28-70 years) in the control group. The mean visual analogue scale score was 0.28 (standard deviation [SD]: 0.61) at 24 hours for the intervention group and 1.84 (SD: 0.37) for the control group (p<0.0001). The mean length of stay was 1.8 days (SD: 0.71 days) for the intervention group and 2.28 days (SD: 0.94 days) for the control group (p=0.15). There were no complications involving catheter placement, leakage or toxicity relating to use of the local anaesthetic. CONCLUSIONS: There was significantly reduced pain with the use of the local anaesthetic infusion pump. The elastomeric pump is a step towards enhanced patient recovery after breast surgery in the case of skin sparing mastectomy and subpectoral tissue expander reconstruction.

Early complications and implant loss in implant-based breast reconstruction with and without acellular dermal matrix (Tecnoss Protexa®): a comparative study.

INTRODUCTION: Acellular dermal matrix (ADM) may improve outcomes in implant-based breast reconstruction, but recent evidence suggests complication rates may be higher when ADM is used. We retrospectively compared early complications and implant loss in implant-based breast reconstruction (BR) with and without ADM to evaluate the safety of the procedure in our centre. METHODS: Case-notes of consecutive women undergoing implant-based BR from May 2011 to November 2012 were retrospectively reviewed. Data were extracted using a standardised pro-forma and the rate of early complications, major complications and implant loss compared between procedure groups. RESULTS: Forty-six implant-based reconstructions were performed for malignancy (n = 31, 67.4%) or prophylaxis (n = 15, 32.6%) in 31 women over the 18-month study period. ADM (Tecnoss Protexa(®), Tecnoss S.r.l.) was used in 31 (67.4%) cases. There were no differences in patient age, BMI, co-morbidities, smoking or chemotherapy between groups, but patients receiving ADM were more likely to have received radiotherapy prior to their reconstruction (n = 6, 30% vs. n = 0, 0%, p = 0.043). The overall rate of early complications was 26.1% (n = 12) but there was no significant difference between procedure groups (standard-n = 4, 27.7% vs. ADM-n = 8, 25.8%; p = 0.950). There were 2 (4.3%) major complications none of which were associated with ADM use (standard-n = 2, 13.3% vs. ADM-n = 0, 0.0%; p = 0.038). There were 6 (13.0%) implant losses of which 4 were in the ADM group (standard-n = 2, 13.3% vs. ADM-n = 4, 12.9%; p = 0.968). All of these were associated with pre-reconstruction radiotherapy. CONCLUSIONS: ADM-assisted implant-based reconstruction with Tecnoss Protexa(®) is safe and may improve outcomes for women by facilitating a single-stage procedure. Robust prospective evaluation is now needed to definitively evaluate the role of ADM in implant-based BR.

Predictive value of abnormally raised serum bilirubin in acute appendicitis: a cohort study.

UNLABELLED: Appendicitis is a common clinical diagnosis aided by biochemical, haematological and radiological investigations. The role of some investigations, such as bilirubin, is controversial but could indicate complicated appendicitis. Accurate diagnosis enables prioritisation of patients on operating lists and a possible reduction in unnecessary investigations. METHODS: This is a retrospective cohort study of 1347 patients who underwent appendicectomy. Statistical analysis of serum bilirubin levels was performed according to histological classification of appendicitis. RESULTS: Mean serum bilirubin levels; perforated/gangrenous appendicitis 20.5 mg/L (SD 12.6), inflamed appendicitis mean 17.5 mg/L (SD CI 11.1), normal appendix mean 12.6 mg/L (7.0). Kruskal-Wallis indicated bilirubin levels were significantly different (H=128.87, df=4, p<.001) between histological groups, and a post hoc analysis with Bonferroni adjustment showed perforated/gangrenous to be significantly higher than all other groups (p<.001). Binary logistic regression combining White Cell Count (WCC) level, C-Reactive Protein (CRP) and Bilirubin levels gave a sensitivity and specificity of .69 with AUROC=.766 (std error .015) for gangrenous/perforated. Assessment according to clinical relevance showed only 30.4% of patients with an abnormally raised bilirubin had gangrenous/perforated appendicitis. CONCLUSIONS: Serum bilirubin does not independently predict perforation/gangrenous appendicitis. Statistical analysis showed differences in mean bilirubin between histological groups however this did not relate to clinical significance as bilirubin levels were still within normal clinical limits. Diagnosis of complicated appendicitis should be made on clinical grounds, with utilization of biochemical/haematological investigations, but there should not be independent reliance on investigations such as bilirubin.

HOSPEX in the antipodes.

The Australian Army recently adopted the British concept of hospital exercise (HOSPEX) as a means of evaluating the capabilities of its deployable NATO Role 2E hospital, the 2nd General Health Battalion. The Australian approach to HOSPEX differs from the original UK model. This article describes the reasons why the Australian Army needed to adopt the HOSPEX concept, how it was adapted to suit local circumstances and how the concept may evolve to meet the needs of the wider Australian Defence Force and our allies.