Commentary on packing vs non-packing of pilonidal sinus cavities after incision and drainage.

Pilonidal sinus disease (PSD) manifests as an inflammatory skin condition typically emerging within the anal cleft. The prevalence of this disease varies in high income countries. This disease is associated with significant physical and psychosocial distress. Surgery is an option for managing PSD; yet, surgical methods vary, and a universally accepted gold standard approach is lacking, leading to current practices that are diverse and subject to ongoing debate. One such point of contention revolves around the decision to use packing or opt for a non-packing approach following surgery. Mohamedahmed et al (2021) conducted a systematic review to evaluate the comparative outcomes of packing versus non-packing of an abscess cavity following incision and drainage of cutaneous abscess on any part of the body. This commentary aims to critically appraise the methods used within the review by Mohamedahmed et al (2021) and expand upon the findings in the context of treatment and management of PSD.

Intra-abdominal cancer risk with abdominal pain: a prospective cohort primary care study.

BACKGROUND: Quantifying cancer risk in primary care patients with abdominal pain informs diagnostic strategies. AIM: To quantify oesophagogastric, colorectal, liver, pancreatic, ovarian, uterine, kidney, and bladder cancer risks associated with newly reported abdominal pain with or without other symptoms, signs, or abnormal blood tests (that is, features) indicative of possible cancer. DESIGN AND SETTING: This was an observational prospective cohort study using Clinical Practice Research Datalink records with English cancer registry linkage. METHOD: The authors studied 125 793 patients aged ≥40 years with newly reported abdominal pain in primary care between 1 January 2009 and 31 December 2013. The 1-year cumulative incidence of cancer, and the composite 1-year cumulative incidence of cancers with shared additional features, stratified by age and sex are reported. RESULTS: With abdominal pain, overall risk was greater in men and increased with age, reaching 3.4% (95% confidence interval [CI] = 3.0 to 3.7, predominantly colorectal cancer 1.9%, 95% CI = 1.6 to 2.1) in men ≥70 years, compared with their expected incidence of 0.88% (95% CI = 0.87 to 0.89). Additional features increased cancer risk; for example, for men, colorectal or pancreatic cancer risk with abdominal pain plus diarrhoea at 60-69 years of age was 3.1% (95% CI = 1.9 to 4.9) predominantly colorectal cancer (2.2%, 95% CI = 1.2 to 3.8). CONCLUSION: Abdominal pain increases intra-abdominal cancer risk nearly fourfold in men aged ≥70 years, exceeding the 3% threshold warranting investigation. This threshold is surpassed for the >60 years age group only with additional features. These results will help direct appropriate referral and testing strategies for patients based on their demographic profile and reporting features. The authors suggest non-invasive strategies first, such as faecal immunochemical testing, with safety-netting in a shared decision-making framework.

Physician associate/assistant contributions to cancer diagnosis in primary care: a rapid systematic review.

BACKGROUND: Symptom recognition and timely referral in primary care are crucial for the early diagnosis of cancer. Physician assistants or associates (PAs) have been introduced in 18 healthcare systems across the world, with numbers increasing in some cases to address primary care physician shortages. Little is known about their impact on suspected cancer recognition and referral. This review sought to summarise findings from observational studies conducted in high income countries on PAs' competence and performance on processes concerned with the quality of recognition and referral of suspected cancer in primary care. METHOD: A rapid systematic review of international peer-reviewed literature was performed. Searches were undertaken on OVID, EMBASE, Web of Science, and CINAHL databases (2009-2019). Studies were eligible if they reported on PA skills, processes and outcomes relevant to suspected cancer recognition and referral. Title and abstract screening was followed by full paper review and data extraction. Synthesis of qualitative and quantitative findings was undertaken on three themes: deployment, competence, and performance. Preliminary findings were discussed with an expert advisory group to inform interpretation. RESULTS: From 883 references, 15 eligible papers were identified, of which 13 were from the USA. Seven studies reported on general clinical processes in primary care that would support cancer diagnosis, most commonly ordering of diagnostic tests (n = 6) and referrals to specialists (n = 4). Fewer papers reported on consultation processes, such as examinations or history taking (n = 3) Six papers considered PAs' competence and performance on cancer screening. PAs performed similarly to primary care physicians on rates of diagnostic tests ordered, referrals and patient outcomes (satisfaction, malpractice, emergency visits). No studies reported on the timeliness of cancer diagnosis. CONCLUSION: This review of peer-reviewed literature combined with advisory group interpretation suggests the introduction of PAs into primary care may maintain the quality of referrals and diagnostic tests needed to support cancer diagnosis. It also highlights the lack of research on several aspects of PAs' roles, including outcomes of the diagnostic process.

Cancer prevention through weight control-where are we in 2020?

Growing data from epidemiological studies highlight the association between excess body fat and cancer incidence, but good indicative evidence demonstrates that intentional weight loss, as well as increasing physical activity, offers much promise as a cost-effective approach for reducing the cancer burden. However, clear gaps remain in our understanding of how changes in body fat or levels of physical activity are mechanistically linked to cancer, and the magnitude of their impact on cancer risk. It is important to investigate the causal link between programmes that successfully achieve short-term modest weight loss followed by weight-loss maintenance and cancer incidence. The longer-term impact of weight loss and duration of overweight and obesity on risk reduction also need to be fully considered in trial design. These gaps in knowledge need to be urgently addressed to expedite the development and implementation of future cancer-control strategies. Comprehensive approaches to trial design, Mendelian randomisation studies and data-linkage opportunities offer real possibilities to tackle current research gaps. In this paper, we set out the case for why non-pharmacological weight-management trials are urgently needed to support cancer-risk reduction and help control the growing global burden of cancer.

Cancer survivorship, excess body fatness and weight-loss intervention-where are we in 2020?

Earlier diagnosis and more effective treatments mean that the estimated number of cancer survivors in the United Kingdom is expected to reach 4 million by 2030. However, there is an increasing realisation that excess body fatness (EBF) is likely to influence the quality of cancer survivorship and disease-free survival. For decades, the discussion of weight management in patients with cancer has been dominated by concerns about unintentional weight loss, low body weight and interventions to increase weight, often re-enforced by the existence of the obesity paradox, which indicates that high body weight is associated with survival benefits for some types of cancer. However, observational evidence provides strong grounds for testing the hypothesis that interventions for promoting intentional loss of body fat and maintaining skeletal muscle in overweight and obese cancer survivors would bring important health benefits in terms of survival outcomes and long-term impact on treatment-related side effects. In this paper, we outline the need for studies to improve our understanding of the health benefits of weight-loss interventions, such as hypocaloric healthy-eating plans combined with physical activity. In particular, complex intervention trials that are pragmatically designed are urgently needed to develop effective, clinically practical, evidence-based strategies for reducing EBF and optimising body composition in people living with and beyond common cancers.

Lost in translation: Knowledge, attitudes and practices in donors experiencing a vasovagal reaction.

BACKGROUND: Vasovagal symptoms have implications for donor safety and retention. This study explored knowledge, attitudes and practices in donors experiencing a vasovagal reaction. MATERIALS AND METHODS: Semi-structured interviews were conducted with donors (n = 30) who experienced a donation-related vasovagal reaction. RESULTS: Donors were unaware of applied muscle tension or fluid loading techniques despite availability of information. Some donors engaged in excessive pre-donation hydration. Procedural knowledge was limited for first-time plasma donors. DISCUSSION: Future interventions should focus on adherence to pre-donation fluid loading and muscle tensing exercises during key donation time-points. Education for new plasma donors also appears important.

Quality of transition to end-of-life care for cancer patients in the intensive care unit.

BACKGROUND: There have been few studies that have evaluated the quality of end-of-life care (EOLC) for cancer patients in the ICU. The aim of this study was to explore the quality of transition to EOLC for cancer patients in ICU. METHODS: The study was undertaken on medical patients admitted to a specialist cancer hospital ICU over 6 months. Quantitative and qualitative methods were used to explore quality of transition to EOLC using documentary evidence. Clinical parameters on ICU admission were reviewed to determine if they could be used to identify patients who were likely to transition to EOLC during their ICU stay. RESULTS: Of 85 patients, 44.7% transitioned to EOLC during their ICU stay. Qualitative and quantitative analysis of the patients' records demonstrated that there was collaborative decision-making between teams, patients and families during transition to EOLC. However, 51.4 and 40.5% of patients were too unwell to discuss transition to EOLC and DNACPR respectively. In the EOLC cohort, 76.3% died in ICU, but preferred place of death known in only 10%. Age, APACHE II score, and organ support, but not cancer diagnosis, were identified as associated with transition to EOLC (p = 0.017, p < 0.0001 and p = 0.001). CONCLUSIONS: Advanced EOLC planning in patients with progressive disease prior to acute deterioration is warranted to enable patients' wishes to be fulfilled and ceiling of treatments agreed. Better documentation and development of validated tools to measure the quality EOLC transition on the ICU are needed.

Characterization of cannabinoid receptor ligands in tissues natively expressing cannabinoid CB2 receptors.

BACKGROUND AND PURPOSE: Although cannabinoid CB2 receptor ligands have been widely characterized in recombinant systems in vitro, little pharmacological characterization has been performed in tissues natively expressing CB2 receptors. The aim of this study was to compare the pharmacology of CB2 receptor ligands in tissue natively expressing CB2 receptors (human, rat and mouse spleen) and hCB2-transfected CHO cells. EXPERIMENTAL APPROACH: We tested the ability of well-known cannabinoid CB2 receptor ligands to stimulate or inhibit [³5S]GTPγS binding to mouse, rat and human spleen membranes and to hCB2-transfected CHO cell membranes. cAMP assays were also performed in hCB2-CHO cells. KEY RESULTS: The data presented demonstrate that: (i) CP 55,940, WIN 55,212-2 and JWH 133 behave as CB2 receptor full agonists both in spleen and hCB2-CHO cells, in both [³5S]GTPγS and cAMP assays; (ii) JWH 015 behaves as a low-efficacy agonist in spleen as well as in hCB2-CHO cells when tested in the [³5S]GTPγS assay, while it displays full agonism when tested in the cAMP assay using hCB2-CHO cells; (iii) (R)-AM 1241 and GW 405833 behave as agonists in the [³5S]GTPγS assay using spleen, instead it behaves as a low-efficacy inverse agonist in hCB2-CHO cells; and (iv) SR 144528, AM 630 and JTE 907 behave as CB2 receptor inverse agonists in all the tissues. CONCLUSION AND IMPLICATIONS: Our results demonstrate that CB2 receptor ligands can display differential pharmacology when assays are conducted in tissues that natively express CB2 receptors and imply that conclusions from recombinant CB2 receptors should be treated with caution.

Acute pancreatitis with pancreatic abscess secondary to sealed jejunal diverticular perforation.

Although most cases of acute pancreatitis are attributed to gallstones or alcohol, many remain idiopathic. The authors describe a case of acute pancreatitis in a 75-year-old gentleman who presented with acute epigastric pain, fevers and shortness of breath. Serum amylase was 2164. CT showed free mesenteric air, and a partly cystic/partly gas-containing mass in the uncinate lobe of the pancreas. Gastrograffin meal revealed duodenal and jejunal diverticular disease, but no contrast leak. Further CT analysis pinpointed fine tracts of air leading from a jejunal diverticulum up toward the pancreas, suggesting causation by a sealed jejunal diverticular perforation. He responded well to intravenous antibiotics and conservative management. Although small bowel diverticular disease is linked to chronic pancreatitis, evidence for association with acute pancreatitis is scarce. The authors believe this is the first reported case of jejunal diverticular disease causing acute pancreatitis, and it highlights micro-perforation as a potential disease mechanism.

Discovery and optimization of 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivatives as a novel class of selective cannabinoid CB2 receptor agonists.

Here, we report the identification and optimization of 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivatives as a novel chemotype with selective cannabinoid CB2 receptor agonist activity. 1 is a potent and selective cannabinoid CB2 receptor agonist (hCB2 pEC(50) = 8.6). The compound was found to be metabolically unstable, which resulted in low oral bioavailability in rat (F(po) = 4%) and possessed off-target activity at the hERG ion channel (pK(i) = 5.5). Systematic modification of physicochemical properties, such as lipophilicity and basicity, was used to optimize the pharmacokinetic profile and hERG affinity of this novel class of cannabinoid CB2 receptor agonists. This led to the identification of 44 as a potent, selective, and orally bioavailable cannabinoid CB2 receptor agonist (hCB2 pEC(50) = 8.0; hERG pK(i) < 4; F(po) = 100%), which was active in a rat spinal nerve ligation model of neuropathic pain.

Dioxo-triazines as a novel series of cathepsin K inhibitors.

A novel dioxo-triazine series of cathepsin K inhibitors was identified from HTS. A rapid exploratory programme led to the discovery of potent and selective cathepsin K inhibitors, typified by compound 24 which displayed IC(50) values of 17nM against catK and >10,000nM in catL, catB and catS assays.

Coronary artery bypass graft surgery: surgical site infection prevention.

This project raised awareness of various factors influencing the risk of developing deep sternal wound infection, postoperative cerebravascular accident, and adverse cardiac events. It elevated attention to evidence-based research and improved outcomes relating to parameters of surgical antibiotic prophylaxis on risks of surgical site infection (SSI) following coronary artery bypass graft (CABG) surgery. Analysis of patient outcomes revealed CABG improvements were statistically significant and showed improvement after implementing improvement strategies. The project suggests improvement projects in hospitals to prevent CABG SSI should focus on a team approach and incorporate evidence-based practices as effective interventions and solutions.

Age-paced parenting newsletters: delivering healthy messages.

There are many sources of information that reinforce the positive and health-enhancing benefits of increasing resources to support parents. Health visitors already provide preventive health care through advice and support on a wide range of health issues, however evidence consistently shows that access to and uptake of care is poorest for those who are most vulnerable. Although the evidence points to the effectiveness of targeting new parents with support systems and information, there are only a few examples of supplying written information on a regular basis to achieve this. This article sets out the background to and the implementation of a feasibility study, which entailed producing and distributing a monthly newsletter to parents within one GP surgery in St Albans. The monthly newsletters provide an accessible service to all new parents allowing the dissemination of age-appropriate health promotion information, and ultimately allow parents to make informed choices that influence the whole family's health. The newsletters adequately address issues and recommendations laid out in several recent important documents and policies.

Lineage infidelity in myeloid cells with TCR gene rearrangement: a latent developmental potential of proT cells revealed by ectopic cytokine receptor signaling.

The most immature lymphoid-committed progenitors in both the bone marrow (common lymphoid progenitor) and thymus (proT1) maintain a latent granulocyte/macrophage (G/M) differentiation potential that can be initiated by signals emanating from exogenously expressed IL-2 receptors. In this study, we investigate at which developmental stage thymocytes lose this G/M differentiation potential. We demonstrate that the next maturational stage after proT1 cells (proT2), but not preT (TN3) cells, can convert cell fate from lymphoid to myeloid in response to ectopic IL-2 receptor signaling in human IL-2Rbeta transgenic mice. It is significant that approximately 10% of clonogenic G/M colonies derived from proT cells of IL-2Rbeta transgenic mice have DJ rearrangement specifically at the Dbeta1 but not Dbeta2 segment in the TCRbeta locus. No TCR gene rearrangement is observed in G/M cells from nontransgenic mice, suggesting that the G/M cells we observe in this system were truly lymphoid-committed before stimulation with IL-2. In addition, Dbeta1 and Dbeta2 DJ rearrangement of the TCRbeta gene may be differentially regulated and thus serve as markers for distinct proT cell maturational stages.