Impact of fixed-dose combination Cal/BD foam on the work productivity of patients with psoriasis: results from the 52-week randomized, double-blind, PSO-LONG trial.

BACKGROUND: Psoriasis contributes to unemployment, work impairment, missed workdays and substantial indirect costs due to lost productivity. Combination Cal/BD foam is the only topical that is approved for long-term maintenance treatment of plaque psoriasis for 52 weeks. This is the first known investigation of the effect of topical psoriasis therapy on productivity. OBJECTIVE: To examine the change in work productivity and activity impairment after 4 weeks of treatment with fixed-dose combination calcipotriol 50 µg/g/betamethasone dipropionate 0.5 mg/g (Cal/BD) foam and observe long-term changes after 52 weeks of long-term management (proactive or reactive treatment). METHODS: This is a post-hoc analysis of the PSO-LONG trial - a phase 3, randomized, double-blind, vehicle-controlled, parallel group, international multi-centre trial of treatment with combination Cal/BD foam. Work and activity impairment due to psoriasis were assessed by the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment Psoriasis (WPAI:PSO) questionnaire at baseline, week 4, week 28 and week 56. The improvement in hours of work productivity was translated into monthly and annual indirect cost savings estimates for patients in Italy, Sweden, United Kingdom, Canada and Germany. RESULTS: Using fixed-dose combination Cal/BD foam for four weeks significantly reduced psoriasis-related work presenteeism, total work productivity impairment (TWPI) and total activity impairment (TAI) over 56 weeks, with significant improvements observed as early as 4 weeks after the baseline visit. The proportion of patients reporting impact on work productivity (as measured by presenteeism and TWPI) and activity impairment (as measured by both DLQI-Q7b and TAI) also decreased. CONCLUSION: Fixed-dose combination Cal/BD foam used for long-term management of psoriasis significantly reduces psoriasis-related work productivity and activity impairment which may result in substantial indirect cost savings. Clinical Trial Registration NCT02899962, EudraCT number: 2016-000556-95.

Safety of day-case paediatric tonsillectomy in England: an analysis of administrative data for the Getting It Right First Time programme.

We used the Hospital Episodes Statistics database to investigate unwarranted variation in the rates Trusts discharged children the same day after scheduled tonsillectomy and associations with adverse postoperative outcomes. We included children aged 2-18 years who underwent tonsillectomy between 1 April 2014 and 31 March 2019. We stratified analyses by category of Trust, non-specialist or specialist, defined as without or with paediatric critical care facilities, respectively. We adjusted analyses for age, sex, year of surgery and aspects of presentation and procedure type. Of 101,180 children who underwent tonsillectomy at non-specialist Trusts, 62,926 (62%) were discharged the same day, compared with 24,138/48,755 (50%) at specialist Trusts. The adjusted proportion of children discharged the same day as tonsillectomy ranged from 5% to 100% at non-specialist Trusts and 9% to 88% at specialist Trusts. Same-day discharge was not independently associated with an increased rate of 30-day emergency re-admission at non-specialist Trusts but was associated with a modest rate increase at specialist Trusts; adjusted probability 8.0% vs 7.7%, odds ratio (95%CI) 1.14 (1.05-1.24). Rates of adverse postoperative outcomes were similar for Trusts that discharged >70% children the same day as tonsillectomy compared with Trusts that discharged <50% children the same day, for both non-specialist and specialist Trust categories. We found no consistent evidence that day-case tonsillectomy is associated with poorer outcomes. All Trusts, but particularly specialist centres, should explore reasons for low day-case rates and should aim for rates >70%.

Clinical relevant pancreatic fistula after pancreatoduodenectomy: when negative amylase levels tell the truth.

Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940-0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81-0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five.

Safety and outcomes of percutaneous tracheostomy in coronavirus disease 2019 pneumonitis patients requiring prolonged mechanical ventilation.

OBJECTIVES: Tracheostomy for coronavirus disease 2019 pneumonitis patients requiring prolonged invasive mechanical ventilation remains a matter of debate. This study analysed the timing and outcomes of percutaneous tracheostomy, and reports our experience of a dedicated ENT-anaesthetics department led tracheostomy team. METHOD: A prospective single-centre observational study was conducted of patients undergoing tracheostomy, who had been diagnosed with coronavirus disease 2019 pneumonitis, between 21st March and 20th May 2020. RESULTS: Eighty-one patients underwent tracheostomy after a median (interquartile range) of 16 (13-20) days of invasive mechanical ventilation. Median follow-up duration was 32 (23-40) days. Of patients, 86.7 per cent were successfully liberated from invasive mechanical ventilation in a median (interquartile range) of 12 (7-16) days. Moreover, 68.7 per cent were subsequently discharged from hospital. On univariate analysis, there was no difference in outcomes between early (before day 14) and late (day 14 or later) tracheostomy. The mortality rate was 8.6 per cent and no deaths were tracheostomy related. CONCLUSION: Outcomes appear favourable when patients are carefully selected. Percutaneous tracheostomy performed via a multidisciplinary approach, with appropriate training, was safe and optimised healthcare resource utilisation.

Co-morbid anxiety and depression impacts on the correlation between symptom and radiological severity in patients with chronic rhinosinusitis.

BACKGROUND: Previous studies have reported that there is little correlation between sino-nasal outcome test (SNOT-22) score in chronic rhinosinusitis (CRS) and objective radiological scoring, although conclusions vary. We aimed to investigate whether comorbid anxiety and depression, which are highly prevalent in patients with CRS may cause symptom amplification and account for the lack of correlation in previous studies. METHODOLOGY: 100 patients with CRS were evaluated using the General Anxiety Disorder-7 (GAD-7), Patient Health Question- naire-9 (PHQ-9) and SNOT-22 questionnaires as well as the Lund Mackay Score (LMS). RESULTS: Overall correlation analysis did not show a significant relationship between SNOT-22 and LMS scores. Subgroup analysis of patients who do not suffer with anxiety and depression showed a significant correlation between SNOT-22 and LMS scores. The nasal domain of the SNOT-22 showed strongest correlation to LMS in this patient group. We also observed a significant difference in both median SNOT-22 and LMS between patients who suffered both anxiety and depression and patients without either co- morbidity. CONCLUSION: When CRS patients who do not have anxiety and depression are analysed in isolation, or when these conditions are controlled in a multivariable regression, there is a significant correlation between radiological findings and symptom score. This correlation is absent in patients with co-morbid anxiety and depression. Anxiety and depression should be considered in patients in whom there is a mismatch in symptom and radiological disease severity as it is associated with symptom amplification.

Proactive multi-modality treatment of Pancreatic Neuroendocrine Tumours (PNETs): Potential survival benefits.

BACKGROUND/OBJECTIVES: Primary and metastatic pancreatic neuroendocrine tumours (PNET) can be treated with combination of surgery, locoregional and systemic therapy. Survival benefits from individual treatments have been well reported, however, the combined outcome from multimodal treatments are not well described in the literature. We report outcomes in a cohort of PNET patients treated with proactive, multimodality therapy. METHODS: 106 patients were identified from a single tertiary referral centre prospective database. Outcomes of treatment were studied, with the primary end point being death from any cause. RESULTS: Median follow-up was 71 months and overall 5-year survival of 62%. In patients with stage I-III disease (51 patients) estimated 5-year survival was 90%. Median survival in patients with stage IV disease was 51 months with an estimated 5-year survival of 40% in this group. A total of 80 patients (75%) had surgery of which 16% suffered complications requiring intervention. There was no perioperative mortality. CONCLUSIONS: This study demonstrates that proactive multimodal treatment is safe and may confer a survival benefit to patients in this cohort compared to historical data.

Propensity score-based analysis of outcomes of laparoscopic versus open liver resection for colorectal metastases.

BACKGROUND: There is a need for high-level evidence regarding the added value of laparoscopic (LLR) compared with open (OLR) liver resection. The aim of this study was to compare the surgical and oncological outcomes of patients with colorectal liver metastases (CRLM) undergoing LLR and OLR using propensity score matching to minimize bias. METHODS: This was a single-centre retrospective study using a prospective database of patients undergoing liver resection for CRLM between August 2004 and April 2015. Co-variates selected for matching included: number and size of lesions, tumour location, extent and number of resections, phase of surgical experience, location and lymph node status of primary tumour, perioperative chemotherapy, unilobar or bilobar disease, synchronous or metachronous disease. Prematching and postmatching analyses were compared. Surgical and oncological outcomes were analysed. RESULTS: Some 176 patients undergoing LLR and 191 having OLR were enrolled. After matching, 133 patients from each group were compared. At prematching analysis, patients in the LLR group showed a longer overall survival (OS) and higher R0 rate than those in the OLR group (P = 0·047 and P = 0·030 respectively). Postmatching analyses failed to confirm these results, showing similar OS and R0 rate between the LLR and OLR group (median OS: 55·2 versus 65·3 months respectively, hazard ratio 0·70 (95 per cent c.i. 0·42 to 1·05; P = 0·082); R0 rate: 92·5 versus 86·5 per cent, P = 0·186). The 5-year OS rate was 62·5 (95 per cent c.i. 45·5 to 71·5) per cent) for OLR and 64·3 (48·2 to 69·5) per cent for LLR. Longer duration of surgery, lower blood loss and morbidity, and shorter postoperative stay were found for LLR on postmatching analysis. CONCLUSION: Propensity score matching showed that LLR for CRLM may provide R0 resection rates and long-term OS comparable to those for OLR, with lower blood loss and morbidity, and shorter postoperative hospital stay.

The need for an objective measure in septorhinoplasty surgery: are we any closer to finding an answer?

OBJECTIVES: To assess the reliability of nasal inspiratory peak flow (NIPF) in providing a clinically accurate objective measure following functional septorhinoplasty by comparing it to the validated disease-specific quality-of-life questionnaire, SNOT-22. Studies so far have demonstrated poor correlation between bilateral NIPF and symptom-specific nasal questionnaires following septorhinoplasty. DESIGN: To perform a prospective comparative analysis between NIPF and the validated disease-specific quality-of-life questionnaire SNOT-22 and to determine whether a correlation exists following septorhinoplasty surgery. SETTING: The Royal National Throat Nose and Ear Hospital, London. PARTICIPANTS: A total of 122 patients (78 males, 44 females; mean age 33.5 ± 12.2 years) were recruited from the senior authors rhinology clinic and underwent functional septorhinoplasty surgery. MAIN OUTCOME MEASURES: Preoperative and postoperative nasal inspiratory peak flow (NIPF) measurements were performed in addition to the completion of three subjective quality-of-life and symptom assessment tool questionnaires; Sinonasal Outcome Test 22 (SNOT-22), Nasal Obstruction Symptom Evaluation (NOSE) and Visual Analogue Scale (VAS: 0-10). RESULTS: The mean preoperative NIPF was 88.2 L/min, and the postoperative value was 101.6 L/min and showed a significant improvement following surgery (P = 0.0064). The mean total SNOT-22 score improved significantly from 48.6 to 26.6 (P < 0.0001); the NOSE score from 14.1 to 6.6 (P < 0.0001); and the Visual Analogue Scale (VAS) blockage score from 6.9 to 3.2 (P < 0.0001). All individual domains assessed showed improvements postoperatively, but no correlation was found between the NIPF and SNOT-22 score. Equally, we did not find a correlation between NIPF and the symptom-specific NOSE questionnaire and the nasal blockage domain on the Visual Analogue Scale (VAS) scale. CONCLUSION: We have demonstrated that NIPF does not correlate with the SNOT-22 disease-specific questionnaire, although both outcomes significantly improve postoperatively. At present, we are still lacking a clinically accurate objective measure of nasal function for the evaluation of patients undergoing septorhinoplasty surgery.

Not just another paediatric neck lump: metastatic cribriform adenocarcinoma of the palate in an adolescent.

OBJECTIVE: This paper reports the case of a 13-year-old girl with a 2-year history of left cervical lymph node swelling that was diagnosed as metastatic cribriform adenocarcinoma of the tongue and minor salivary gland. CASE REPORT: A 13-year-old girl with a left, level II cervical lymph node underwent excisional biopsy after an ultrasound suggested suspicious features. The histology indicated polymorphous low-grade adenocarcinoma, and a primary lesion in the left palate was identified. The patient underwent left maxillectomy, neck dissection and reconstruction. Histological analysis of resection specimens led to a revised diagnosis of cribriform adenocarcinoma of the tongue and minor salivary gland. CONCLUSION: Cribriform adenocarcinoma of the tongue and minor salivary gland has recently been described as a separate entity to polymorphous low-grade adenocarcinoma in light of histological and behavioural differences, including higher rates of metastasis at presentation. This is the first report in the world literature of an adolescent with this entity. It is possible that some previous reports of polymorphous low-grade adenocarcinoma in childhood would have been more accurately described as cribriform adenocarcinoma of the tongue and minor salivary gland.

Validation of the sino-nasal outcome test-23 in septorhinoplasty surgery.

BACKGROUND: There has been a great expansion in patient-based outcome measures to face the ever-increasing demand to demonstrate surgical efficacy. However, surgeons have not adopted until now any systematic outcome instrument. The 22-item Sino-Nasal Outcome Test (SNOT-22) is a validated sinonasal outcome score in sinonasal and septorhinoplasty surgery but does not measure aesthetic outcome. The aim of this paper is to validate a modification to the Sino-Nasal Outcomes Test-22 (SNOT-22) with a new question regarding the shape of the nose (SNOT-23). METHODOLOGY: We conducted a prospective cohort study on 69 consecutive patients undergoing septorhinoplasty and a control group of healthy volunteers. Reproducibility, responsiveness to treatment, known group differences and validity of the SNOT-23 were analysed. Scores were compared to visual analogue scales, nasal obstruction symptoms evaluation (NOSE) score and nasal inspiratory peak flow. RESULTS: SNOT-23 has good test-retest reliability and is a valid outcome measure for assessing response to surgery especially with regards to shape of the nose and nasal obstruction when compared to other patient reported measures. CONCLUSION: SNOT-23 is a valid and reliable tool that can be easily used in routine clinical practice to assess the functional and aesthetic outcomes from septorhinoplasty surgery. The SNOT-23 could be adopted as a universal, easy to use tool in rhinology clinics for the assessment of response to septorhinoplasty and sinus surgery.

Dendritic cell biology, dysfunction and immunotherapy in gastrointestinal cancers.

Gastrointestinal (GI) cancers make up a significant proportion of newly diagnosed malignant disease. The five-year survival for these GI cancers is poor. Anti-cancer host defences are thought to play a role in these cancers, albeit they are suboptimal. Novel immunotherapies are being introduced to treat such patients. This review describes basic cell biology of dendritic cells, as they are thoughtto play a key role in generating effective anti-tumour responses. Dendritic cell dysfunction in patients with various cancers is documented and immunotherapy using dendritic cells in a range of GI cancers is described and discussed

The effect of jaundice on the generation of anti-gastrin antibodies in G17DT immunized patients with advanced pancreatic cancer.

AIM: The aim of this study was to determine the ability of G17DT to generate anti-gastrin antibodies in jaundiced patients with biliary obstruction due to advanced pancreatic cancer. METHODS: G17DT was administered to 41 patients with advanced pancreatic adenocarcinoma by intramuscular (i.m.) injection at a dose of 250mcg at weeks 0, 1 and 3 of the study. RESULTS: Thirty-five of 41 patients participating in the study were categorized as responders in terms of their gastrin-17 antibody response. There was no correlation between the maximum G17 antibody response and the bilirubin level at either week 0 or week 12. The median survival of patients from the time of the first injection of G17DT was 204 days with 25% of patients surviving for or=305 days. CONCLUSION: This study shows that G17DT administered to jaundiced patients with advanced pancreatic cancer is immunogenic and well tolerated.

The role of gastrin in colorectal carcinogenesis.

Colorectal cancer is one of the leading causes of cancer-associated death in the United States and United Kingdom. In England and Wales, it is the second most common cancer in women and the third most common in men. Currently, treatment options for this debilitating disease are limited and surgical resection is the only curative treatment available. Despite rapid advances in surgery, as well as in adjuvant therapies such as radiotherapy and chemotherapy, there has been only a relatively modest improvement in mortality. The majority of colorectal cancers are epithelial-derived adenocarcinomas and arise from benign adenomas through the gain of mutations in key genes. Gastrin, an important polypeptide hormone, responsible for gastric acid secretion has been found to be involved in tumourigenesis in the gastrointestinal tract. When aberrantly expressed, the gastrin and gastrin/CCK-2 receptor genes can mediate powerful down stream events; the gastrin gene can impart anti-apoptotic properties while the gastrin/CCK-2 receptor can activate the transcription of a number of factors including ligands of the epidermal growth factor (EGF) receptor, the REG protein and matrix metalloproteinases (MMPs). In colonic tumourigenesis, gene expression of both gastrin and the gastrin/CCK-2 receptor is activated within epithelial cells at an early stage of the adenoma-carcinoma sequence. This review details the role played by gastrin in the adenoma-carcinoma sequence of colorectal carcinogenesis.

Stimulation of inorganic-phosphate incorporation into phosphatidylinositol in rat thoracic aorta mediated through V1-vasopressin receptors.

Vasopressin stimulates the incorporation of [32P]Pi into phosphatidylinositol but not into other phospholipids in rat thoracic aorta strips. The relative abilities of three vasopressin analogues to stimulate phosphatidylinositol labelling in rat aorta are similar to their relative pressor potencies in vivo and to their relative potencies in stimulating the metabolism of rat hepatocytes, but very different from their relative antidiuretic potencies. The vasopressor antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid),8-arginine]vasopressin competitively inhibits [Arg8]vasopressin-stimulated phosphatidylinositol labelling in rat aorta with a pA2 of 8.1. It is concluded that the Ca2+-mobilizing vasopressin receptors (V1-receptors) of the rat aorta stimulate phosphatidylinositol metabolism, probably by enhancing phosphatidylinositol breakdown.