Improving communication during damage control surgery: a survey of adult major trauma centres in England.

INTRODUCTION: Deficiencies in non-technical skills can severely impede the functioning of teams in high-intensity scenarios, such as in damage control surgery for the critically injured trauma patient. Truncated preoperative checklists, modified from the standard World Health Organization preoperative checklist, and situational reporting at intervals during surgery are long-established practices in the military, and are recommended in the National Health Service guidelines on major incidents. These tools allow the multiprofessional team to create a shared mental model of the anaesthetic and operative plan, thereby improving team efficiency. Our aim was to establish whether adult major trauma centres in England are using truncated preoperative checklists and situational reporting for damage control surgery. METHODS: An online survey was devised and distributed via the national programme of care for trauma in November 2020. RESULTS: Responses were received from all 23 adult major trauma centres in England. Nine centres (39.1%) reported using a truncated preoperative checklist for damage control surgery albeit in a variety of formats. Common components were blood products received and/or available, presence of allergies, tranexamic acid and antibiotic administration, availability of viscoelastic tests, equipment required, availability of cell saver, role allocation and reference to other personnel needed, and discussion of the plan. Twelve centres (52.2%) have formal policies in place for situational reporting. Again, these were in multiple formats but all focused on patient physiology to direct surgical planning. CONCLUSIONS: We have identified key components to advanced communication aids for damage control surgery, providing a foundation on which other major trauma centres can build their own versions of these potentially lifesaving tools.

The impact of mepolizumab on sleep impairment in CRSwNP: post hoc analyses of SYNAPSE and MUSCA.

BACKGROUND: The impact of mepolizumab on impaired sleep, one of the most bothersome symptoms in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), is unknown. This study aimed to determine the effect of mepolizumab and impact of comorbid upper and lower airway disease and blood eosinophil count (BEC) on sleep-/fatigue-related outcomes in CRSwNP. METHODS: This was an analysis of the Phase III SYNAPSE and MUSCA (NCT03085797/NCT02281318) trials of mepolizumab in patients with severe CRSwNP and severe asthma, respectively. Endpoints included change from baseline in 22-item Sino-Nasal Outcome Test (SNOT-22) sleep and fatigue domains (SYNAPSE: Weeks 24 and 52; MUSCA: Week 24) in the overall populations and post hoc subgroups (SYNAPSE: comorbid asthma, comorbid non-steroidal anti-inflammatory drug-exacerbated respiratory disease [N-ERD] and BEC; MUSCA: comorbid CRSwNP). RESULTS: In SYNAPSE, 289/407 patients with severe CRSwNP had comorbid asthma, 108 had N-ERD, and 278 had BEC ≥300 cells/µL. In MUSCA, 105/551 patients with severe asthma had comorbid CRSwNP. Baseline sleep and fatigue scores were worse in patients with comorbid airway disease and higher BEC. Improvements from baseline in sleep and fatigue scores were greater with mepolizumab versus placebo at Week 52 in SYNAPSE (difference in least squares mean change: -2.7 [sleep], -3.4 [fatigue], and Week 24 in SYNAPSE (-1.6 and -2.2) and MUSCA (-0.8 and -1.2), with consistent results across comorbidity and BEC subgroups. CONCLUSION: Mepolizumab improves sleep and fatigue in severe CRSwNP, irrespective of comorbid airway disease and BEC, with consistent effects in severe asthma with and without comorbid CRSwNP.

Prevalence of clinically significant prostate carcinoma in Prostate Imaging Reporting and Data System (PIRADS) 3 lesions detected in the peripheral zone on biparametric magnetic resonance imaging (MRI)-a local experience.

AIM: The aim of this study was to determine whether biparametric magnetic resonance imaging (MRI) is effective in the diagnosis of clinically significant prostate cancer in prostate peripheral zone Prostate Imaging Reporting and Data System (PIRADS) 3 lesions without the use of dynamic contrast enhancement. MATERIALS AND METHODS: Patients who underwent biparametric MRI over a 12-month period from January 2022 to December 2022 and were diagnosed with PIRADS 3 lesion in the peripheral zone were included in the study. No patient received dynamic contrast enhancement. Histological analysis was done after performing local anesthetic transperineal biopsy to determine detection rate of clinically significant prostate cancer. Prostate-specific antigen density (PSAD) and biopsy complication rates were also reviewed. RESULTS: Sixty-one out of 688 MRIs (8.8%) performed over the study period had a PIRADS 3 lesion in the peripheral zone where contrast is supposed to add value. Fifty-eight of the 61 went ahead to biopsy, and csPCa (Gleason score: ≥3 + 4, with a max core length of ≥6 mm and above) was diagnosed in 17%. Among those diagnosed with csPCa, 80% had a PSAD of >0.15 ng/ml/cc. No postbiopsy complications were reported. CONCLUSION: Biparametric MRI without contrast offers a reliable alternative to multiparametric MRI with minimum or neglible impact on clinically significant prostate cancer (csPCa) diagnosis in peripheral zone PIRADS 3 lesions, especially when used in conjunction with other factors such as PSAD. There is potential to address health economics and patient burden in prostate cancer investigation.

Efficacy of Ultrasound for the Detection of Possible Fatty Liver Disease in Children.

Pediatric MASLD (previously referred to as NAFLD) incidence has continued to rise along with the obesity pandemic. Pediatric MASLD increases the risk of liver fibrosis and cirrhosis in adulthood. Early detection and intervention can prevent and reduce complications. Liver biopsy remains the gold standard for diagnosis, although imaging modalities are increasingly being used. We performed a retrospective study of 202 children seen in a pediatric gastroenterology clinic with a complaint of abdominal pain, elevated liver enzymes or MASLD, or a combination of the three to evaluate screening methods for MASLD. A total of 134 of the 202 patients included in the study underwent laboratory testing and abdominal ultrasound. Ultrasound images were reviewed with attention to liver size and echotexture by a fellowship-trained pediatric radiologist for liver size and echotexture. Overall, 76.2% of the initial radiology reports correctly identified hepatomegaly based on age and 75.4% of the initial radiology reports correctly described hepatic echogenicity that was consistent with increased hepatic fat deposition. Use of screening ultrasound in concert with other clinical evaluations can be helpful to identify children at risk of MASLD. Utilizing ranges for liver span according to age can help to diagnose hepatomegaly, and understanding how to identify hepatic echogenicity is important for identifying possible hepatic steatosis.

Iron limitation induces motility in uropathogenic E. coli CFT073 partially through action of LpdA.

More than half of women will experience a urinary tract infection (UTI) with most cases caused by uropathogenic Escherichia coli (UPEC). Bacterial swimming motility enhances UPEC pathogenicity, resulting in more severe disease outcomes including kidney infection. Surprisingly, the connection between motility and iron limitation is mostly unexplored despite the lack of free iron available in the host. We sought to investigate a potential connection between iron restriction and regulation of motility in UPEC. We cultured E. coli CFT073, a prototypical UPEC strain, under iron limitation and observed that CFT073 had elevated fliC (flagella) promoter activity, and this iron-specific response was repressed by the addition of exogenous iron. We confirmed increased flagellar expression in CFT073 by measuring fliC transcript, FliC protein, and surface-expressed flagella under iron-limited conditions. Interestingly, known motility regulator flhDC did not have altered transcription under these conditions. To define the regulatory mechanism of this response, we constructed single knockouts of eight master regulators and found the iron-regulated response was lost in crp, arcA, and fis mutants. Thus, we focused on the five genes regulated by all three regulators. Of the five genes knocked out, the iron-regulated motility response was most strongly dysregulated in the lpdA mutant, which also resulted in significantly lowered fitness in the murine model of ascending UTI, both against the WT and a non-motile fliC mutant. Collectively, we demonstrated that iron-mediated motility in CFT073 is partially regulated by lpdA, which contributes to the understanding of how uropathogens differentially regulate motility mechanisms in the iron-restricted host. IMPORTANCE: Urinary tract infections (UTIs) are ubiquitous and responsible for over five billion dollars in associated health care costs annually. Both iron acquisition and motility are highly studied virulence factors associated with uropathogenic Escherichia coli (UPEC), the main causative agent of uncomplicated UTI. This work is innovative by providing mechanistic insight into the synergistic relationship between these two critical virulence properties. Here, we demonstrate that iron limitation has pleiotropic effects with consequences that extend beyond metabolism and impact other virulence mechanisms. Indeed, targeting iron acquisition as a therapy may lead to an undesirable enhancement of UPEC pathogenesis through increased motility. It is vital to understand the full breadth of UPEC pathogenesis to adequately respond to this common infection, especially with the increase of antibiotic-resistant pathogens.

Early onset metastatic colorectal cancer in Australia.

BACKGROUND: Colorectal cancer (CRC) incidence and mortality rates have been increasing among young patients (YP), for uncertain reasons. It is unclear whether YP have a distinct tumor biology or merit a different treatment approach to older patients (OP). METHODS: We reviewed prospectively collected data from consecutive patients with metastatic CRC (MCRC) enrolled in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australian registry. Clinicopathological features, treatment and survival outcomes were compared between YP (<50 years) and OP (≥50 years). RESULTS: Of 3692 patients diagnosed August 2009 - March 2023, 14 % (513) were YP. YP were more likely than OP to be female (52% vs. 40 %, P < 0.0001), have ECOG performance status 0-1 (94% vs. 81 %, P < 0.0001), to have a left-sided primary (72% vs. 63 %, P = 0.0008) and to have fewer comorbidities (90% vs. 60 % Charleston score 0, P < 0.0001). There were no differences in the available molecular status, which was more complete in YP. YP were more likely to have de novo metastatic disease (71% vs. 57 %, P < 0.0001). YP were more likely to undergo curative hepatic resection (27% vs. 17 %, P < 0.0001), to receive any chemotherapy (93% vs. 78 % (P < 0.0001), and to receive 3+ lines of chemotherapy (30% vs. 24 % (P < 0.0034)). Median first-line progression free survival (10.2 versus 10.6 months) was similar for YP vs OP, but overall survival (32.1 versus 25.4 months, HR = 0.745, P < 0.0001) was longer in YP. CONCLUSION: Known prognostic variables mostly favored YP versus OP with newly diagnosed mCRC, who were also more heavily treated. Consistent with this, overall survival outcomes were improved. This data does not support that CRC in YP represent a distinct subset of mCRC patients, or that a modified treatment approach is warranted.

The implementation of a hepatitis C testing service in community pharmacies: I-COPTIC consensus statement.

OBJECTIVES: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. STUDY DESIGN: This was a modified Delphi process. METHODS: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. RESULTS: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. CONCLUSIONS: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.

Co-infection of Helicobacter pylori and intestinal parasites in children of selected low-income communities in Lagos State, Nigeria.

Helicobacter pylori and intestinal parasites cause gastrointestinal diseases with a high prevalence in children in resource limited developing countries. There is paucity of information in Nigeria on co-infection of H. pylori and intestinal parasites. The study was conducted to determine the prevalence of H. pylori and parasite co-infection in children from selected low-income communities in Lagos, Nigeria. Fecal samples were collected from 151 healthy children aged ≤11 years across six low-income communities in Lagos. H. pylori was detected using stool antigen test and conventional PCR assay, intestinal parasites were detected using formol-ether concentration and nested PCR assay. Structured questionnaires were administered to parents and legal guardians of the children by an interviewer to collect relevant data on demographic and lifestyle factors. The prevalence of H. pylori was 31.79% (48), with a higher prevalence in children aged 2-3 years. The prevalence of intestinal parasites was 21.19% (32) with the lowest frequency found in children aged 8-9 years. The parasites detected include: A. lumbricoides (10.6%), G. intestinalis (7.3%), hookworm (1.99%), E. histolytica (0.66%), S. mansoni (0.66%). There was co-infection prevalence of 10.6% (16) which was associated with the parasites: G. intestinalis (7.3%) and A. lumbricoides (3.97%). Polyparasitism with G. intestinalis and A. lumbricoides was reported in 2 children infected with H. pylori. This study which is the first reported in Lagos established a low prevalence of H. pylori and intestinal parasite co-infection in children and provides better understanding of the epidemiology of H. pylori infection associated with intestinal parasites in Nigeria.

Mepolizumab improves sense of smell in severe chronic rhinosinusitis with nasal polyps: SYNAPSE.

BACKGROUND: Loss of smell is one of the most bothersome and difficult-to-treat symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: SYNAPSE was a 52-week Phase III study of 4-weekly mepolizumab (100 mg subcutaneously) plus standard of care in adults with severe bilateral CRSwNP. This post hoc analysis assessed changes from baseline to study end in loss of smell visual analogue scale (VAS) symptom score, in patients stratified by several baseline clinical characteristics. SinoNasal Outcomes Test (SNOT)-22 sense of smell/taste item and University of Pennsylvania Smell Identification Test (UPSIT) scores were also assessed. RESULTS: SYNAPSE enrolled 407 patients (mepolizumab=206; placebo=201) with impaired sense of smell at baseline. Improvements from baseline to study end in loss of smell VAS score were greater with mepolizumab versus placebo (treatment difference: -0.37) and most notable in patients with fewer or more recent prior surgeries (treatment difference: 1 vs 2 vs more than 2 prior surgeries,-1.29 vs -0.23 vs -0.07; =3 years since last surgery, -.89 vs 0.22). Approximately 25% of patients had baseline UPSIT scoresavailable; among those scoring =19 by study end. The SNOT-22 sense of smell/taste item score improved with mepolizumab versus placebo. CONCLUSIONS: Mepolizumab treatment improved patients' perceived sense of smell, as measured by loss of smell VAS score and SNOT-22 sense of smell/taste item score in patients with severe refractory CRSwNP.

Current preconception care practice in the Netherlands - An evaluation study among birth care professionals.

OBJECTIVE: To evaluate the current practice of preconception care in the Netherlands and the perceptions of birth care professionals concerning preconception care. METHODS: We have developed a digital questionnaire and conducted a cross-sectional study by distributing the questionnaire among 102 organisations: 90 primary care midwifery practices and obstetric departments of 12 hospitals in the Southwest region of the Netherlands between December 2020 and March 2021. One birth care professional per organization was asked to complete the questionnaire. Descriptive statistics were used to present the results. FINDINGS: Respondents of eighty-three organisations (81.4 %) filled in the questionnaire, of whom 74 respondents were independent primary care midwives and 9 respondents were obstetricians. Preconception care mostly consisted of an individual consultation in which personalized health and lifestyle advice was given. Among the respondents, 44.4 % reported that the organization had a preconception care protocol. The way in which the consultation was carried out, as well as the health and lifestyle related questions asked, differed between respondents. More than 85 % of the respondents inquire about the following possible risk factors for complications: maternal illnesses, obstetric history, folic acid supplement intake, alcohol intake, smoking, substance abuse, hereditary disease, prescription medication, dietary habits, overweight, and birth defects in the family. The respondents acknowledged that preconception care should be offered to all couples who wish to become pregnant, as opposed to offering preconception care only to those with an increased risk of complications. Still, respondents do not receive many questions regarding the preconception period or requests for preconception care consultations. KEY CONCLUSION: Birth care professionals acknowledge the need for preconception care for all couples. In the Netherlands, preconception care consists mostly of an individual consultation with recommendations for health and lifestyle advice. However, the identification of risk factors varies between birth care professionals and less than half of the respondents indicate that they have a protocol available in their practice. Furthermore, the demand of parents-to-be for preconception care is low. More research, that includes more obstetricians, is necessary to investigate if there is a difference between the care provided by primary care midwives and obstetricians. IMPLICATIONS FOR PRACTICE: To increase the awareness and uptake of preconception care, it would be prudent to emphasize its importance to parents-to-be and professionals, and actively promote the use of widespread, standardized protocols for birth care professionals.

Altered motility in response to iron-limitation is regulated by lpdA in uropathogenic E. coli CFT073.

More than half of all women will experience a urinary tract infection (UTI) in their lifetime with most cases caused by uropathogenic Escherichia coli (UPEC). Bacterial motility enhances UPEC pathogenicity, resulting in more severe disease outcomes including kidney infection. Surprisingly, the connection between motility and iron limitation is mostly unexplored, despite the lack of free iron available in the host. Therefore, we sought to explore the potential connection between iron restriction and regulation of motility in UPEC. We cultured E. coli CFT073, a prototypical UPEC strain, in media containing an iron chelator. Under iron limitation, CFT073 had elevated fliC (flagella) promoter activity, driving motility on the leading edge of the colony. Furthermore, this iron-specific response was repressed by the addition of exogenous iron. We confirmed increased flagella expression in CFT073 by measuring fliC transcript, FliC protein, and surface-expressed flagella under iron-limited conditions. To define the regulatory mechanism, we constructed single knockouts of eight master regulators. The iron-regulated response was lost in crp, arcA, and fis mutants. Thus, we focused on the five genes regulated by all three transcription factors. Of the five genes knocked out, the iron-regulated motility response was most strongly dysregulated in an lpdA mutant, which also resulted in significantly lowered fitness in the murine model of ascending UTI. Collectively, we demonstrated that iron-mediated motility in CFT073 is regulated by lpdA , which contributes to the understanding of how uropathogens differentially regulate motility mechanisms in the iron-restricted host. Importance: Urinary tract infections (UTIs) are ubiquitous and responsible for over five billion dollars in associated health care costs annually. Both iron acquisition and motility are highly studied virulence factors associated with uropathogenic E. coli (UPEC), the main causative agent of uncomplicated UTI. This work is innovative by providing mechanistic insight into the synergistic relationship between these two critical virulence properties. Here, we demonstrate that iron limitation has pleiotropic effects with consequences that extend beyond metabolism, and impact other virulence mechanisms. Indeed, targeting iron acquisition as a therapy may lead to an undesirable enhancement of UPEC pathogenesis through increased motility. It is vital to understand the full breadth of UPEC pathogenesis to adequately respond to this common infection, especially with the increase of antibiotic resistant pathogens.

Psychedelics: Threshold of a Therapeutic Revolution.

This Special Issue of Neuropharmacology on psychedelics provides a timely and comprehensive update on progress following the previous Neuropharmacology Special Issue "Psychedelics: New Doors, Altered Perceptions". Remarkable advances have been made in basic and clinical research on psychedelics in the five years since 2018. It is partly based on the seminar series focused on psilocybin organized by the National Institutes of Health (NIH), USA from April to June 2021, the "NIH Psilocybin Research Speaker Series". Participants were world leading experts, including scientists, medical practitioners, clinical psychologists and oncologists, and attendees from additional disciplines of patient advocacy, law, government science policy and regulatory policy. To provide a global perspective, their contributions are complemented with reviews by some of the world's most eminent scientists in the field. The US Food and Drug Administration (FDA) has granted two breakthrough therapy designations for psilocybin in treatment resistant depression (TRD) in 2018 and major depressive disorder (MDD) in 2019, as well as for MDMA for the treatment of post-traumatic stress disorder (PTSD) in 2017. Clinical trials are in progress to assess the therapeutic value of psilocybin in MDD and TRD, and in other indications such as cancer-related anxiety and depression, anorexia, PTSD, substance use disorders and various types of chronic pain. The contributors' insights should assist basic and applied science for transition of psychedelics from bench to potential mainstream therapies. The implications are global, because FDA approval of these new medicines will increase international interest and efforts.

Determining the neurocognitive profile of children with tuberous sclerosis complex within the Western Cape region of South Africa.

BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder associated with a wide spectrum of cognitive impairments that can often result in impaired academic, social and adaptive functioning. However, studies investigating TSC have found it difficult to determine whether TSC is associated with a distinct cognitive phenotype and more specifically which aspects of functioning are impaired. Furthermore, children with TSC living in low-income and middle-income countries, like South Africa, experience additional burdens due to low socio-economic status, high mortality rates and poor access to health care and education. Hence, the clinical population of South Africa may vary considerably from those populations from high-income countries discussed in the literature. METHODS: A comprehensive neuropsychological battery composed of internationally recognised measures examining attention, working memory, language comprehension, learning and memory, areas of executive function and general intellectual functioning was administered to 17 children clinically diagnosed with TSC. RESULTS: The exploration of descriptive data indicated generalised cognitive difficulties in most cognitive domains, aside from memory. With only two participants performing in the average to above-average ranges, the rest of the sample showed poor verbal comprehension, perceptual reasoning, working memory, processing speed, disinhibition, and problems with spatial planning, problem solving, frustration tolerance, set shifting and maintaining a set of rules. Furthermore, correlational findings indicated several associations between socio-demographic and cognitive variables. CONCLUSIONS: Importantly, this is the first study to comprehensively examine multiple domains of neurocognitive functioning in a low-resource setting sample of children with TSC. Current study findings showed that children with TSC have generalised impairments across several cognitive domains, rather than domain-specific impairments. Therefore, although examining individual aspects of cognition, such as those found in previous literature, is important, this approach is limiting. With a comprehensive assessment, including understanding the associations between domains, appropriate and directed support can be provided to ensure all aspects of development are addressed and considered.

Evaluating treatment response to mepolizumab in patients with severe CRSwNP.

BACKGROUND: The SYNAPSE study (NCT03085797) demonstrated that mepolizumab decreased nasal polyp (NP) size and nasal obstruction in patients with chronic rhinosinusitis with NP (CRSwNP). METHODS: SYNAPSE, a randomized, double-blind study, included patients with recurrent, refractory, severe CRSwNP, eligible for repeated surgery despite receiving standard of care (SoC). Patients received 4-weekly mepolizumab 100 mg or placebo subcutaneously plus SoC for 52 weeks. This post hoc analysis further characterized treatment responses and association with patient characteristics. The proportion of patients meeting any and each of five response criteria indicating improvement in disease-specific quality of life, NP size, nasal obstruction, loss of smell, and overall symptoms at Weeks 24 and 52, were assessed in subgroups: 1) no surgery; 2) neither surgery nor systemic corticosteroids (SCS). RESULTS: Of 407 patients in the intention-to-treat population, 381 and 343 patients had no sinus surgery by Weeks 24 and 52, respectively. More mepolizumab- versus placebo-treated patients without surgery by Weeks 24 and 52 met each response criteria. Of the mepolizumab-treated patients without surgery by Week 24, 109 (55%) responded across >=3 criteria, increasing to 126 (67%) by Week 52. Similar response trends were seen for patients with neither surgery nor SCS by Weeks 24 and 52. At either timepoint, there were no major differences in baseline characteristics between mepolizumab-treated full- (5/5 categories) and non-responders (0/5 categories). CONCLUSIONS: Most patients who completed SYNAPSE required neither surgery nor SCS use and in addition achieved a progressive and sustained clinical response to mepolizumab underscoring the therapeutic benefits of mepolizumab in severe CRSwNP.

Women's Understanding of Windows of Susceptibility and the Role of the Environment in Breast Cancer Risk.

Emerging evidence suggests women who are exposed to harmful environmental exposures, especially during certain critical periods across the lifespan, may increase their breast cancer risk. Such windows of susceptibility (WoS) occur throughout a woman's lifetime, during which she is especially vulnerable to the effects of harmful environmental exposures. This interaction makes the reduction of harmful environmental toxicants during those time periods a priority for community health promotion. Communicating about environmental exposures and their impact on women's health requires an assessment of sense-making around, and understanding of, the link between breast cancer and the environment. To that end, focus groups were conducted to assess the themes that emerge when women make sense of (a) their own breast cancer risk, (b) the environment-cancer connection, and (c) WoS. Results provide insight into how women understand these issues which can inform messaging strategies focused on reducing harmful environmental exposures. Implications are discussed within the context of communication efforts tailored to educate women, particularly mothers with daughters in the prepubertal and pubertal WoS who are particularly vulnerable to harmful environmental exposures.

The reorganisation of emergency general surgery services during the COVID-19 pandemic in the UK: outcomes of delayed presentation, socio-economic deprivation and Black, Asian and Minority Ethnic patients.

INTRODUCTION: The COVID-19 pandemic is a global public health emergency. Lockdown restrictions and the reconfiguration of healthcare systems to accommodate an increase in critical care capacity have had an impact on 'non-COVID' specialties. This study characterises the utilisation of emergency general surgery (EGS) services during the UK lockdown period at a university teaching hospital with a catchment population that represents one of the most deprived and ethnically diverse areas in the UK. METHODS: EGS admissions during the UK lockdown period (March to May 2020) were compared with the same period in 2019. Patient demographics were recorded together with clinical presentation, hospital stay and treatment outcomes, and readmission data. RESULTS: The study included 645 patients, comprising 223 in the COVID-19 period and 422 in the non-COVID-19 period. There was no difference in age, sex, comorbidity or socio-economic status. A lower proportion of patients of Black, Asian and Minority Ethnicity (BAME) were admitted during the pandemic (20.6% vs 35.4%, p < 0.05). The duration of symptoms prior to presentation was longer, and admission clinical parameters and serum inflammatory markers. More patients presented with an acute kidney injury (9.9% vs 4.7%, p = 0.012). There was no difference in perioperative outcomes or 30-day mortality, but more patients were readmitted following conservative management (10.6% vs 4.7%, p = 0.023). CONCLUSIONS: The reorganisation of EGS to a senior-led model has been successful in terms of outcomes and access to treatment despite a more unwell population. There was a significantly lower proportion of BAME admissions suggesting additional barriers to healthcare access under pandemic lockdown conditions.

Retrospective analysis of the management strategies for surgical site infection post total hip or knee arthroplasty from tertiary care centres in Edmonton, Alberta.

BACKGROUND: Surgical site infection (SSI) following hip or knee arthroplasty poses a serious health and economic burden. AIM: To evaluate SSI management strategies and outcomes to help address this problem. METHODS: A retrospective cohort study was undertaken of adults undergoing primary total hip or knee arthroplasty who were identified to have a complex SSI by infection prevention and control surveillance audit. Audits identified SSI within 90 days of arthroplasty. Patients at two tertiary referral centres in Edmonton, Alberta, Canada from 2012 to 2019 were included, and SSI cases were followed for 2 years. FINDINGS: In total, 240 SSIs were identified. Of these, 202 (84%) cases were managed with debridement with antibiotics and implant retention (DAIR), of which 71% achieved cure. The use of any topical intra-operative antibiotic in DAIR was not associated with improved outcome (odds ratio 1.68, 95% confidence interval 0.91-3.10; P=0.097). DAIR performed 31-90 days after arthroplasty had a lower chance of cure compared with DAIR performed within 30 days of arthroplasty; however, this difference was not significant (60 vs 73%; P=0.123). Initial treatment failures requiring additional surgery had a 51% cure rate. The majority (78%) of treatment failures initially managed with DAIR ultimately required two-stage revision. CONCLUSIONS: This study provides insight from a population-based perspective into the surgical management of SSI after primary total hip or knee arthroplasty in a large cohort. Additionally, SSIs that had initial management failure were followed. These data can inform future studies, such as the economic burden associated with these infections, and may be used to plan interventions to optimize SSI management.

Nitrogen and Iron Availability Drive Metabolic Remodeling and Natural Selection of Diverse Phytoplankton during Experimental Upwelling.

Nearly half of carbon fixation and primary production originates from marine phytoplankton, and much of it occurs in episodic blooms in upwelling regimes. Here, we simulated blooms limited by nitrogen and iron by incubating Monterey Bay surface waters with subnutricline waters and inorganic nutrients and measured the whole-community transcriptomic response during mid- and late-bloom conditions. Cell counts revealed that centric and pennate diatoms (largely Pseudo-nitzschia and Chaetoceros spp.) were the major blooming taxa, but dinoflagellates, prasinophytes, and prymnesiophytes also increased. Viral mRNA significantly increased in late bloom and likely played a role in the bloom's demise. We observed conserved shifts in the genetic similarity of phytoplankton populations to cultivated strains, indicating adaptive population-level changes in community composition. Additionally, the density of single nucleotide variants (SNVs) declined in late-bloom samples for most taxa, indicating a loss of intraspecific diversity as a result of competition and a selective sweep of adaptive alleles. We noted differences between mid- and late-bloom metabolism and differential regulation of light-harvesting complexes (LHCs) under nutrient stress. While most LHCs are diminished under nutrient stress, we showed that diverse taxa upregulated specialized, energy-dissipating LHCs in low iron. We also suggest the relative expression of NRT2 compared to the expression of GSII as a marker of cellular nitrogen status and the relative expression of iron starvation-induced protein genes (ISIP1, ISIP2, and ISIP3) compared to the expression of the thiamine biosynthesis gene (thiC) as a marker of iron status in natural diatom communities. IMPORTANCE Iron and nitrogen are the nutrients that most commonly limit phytoplankton growth in the world's oceans. The utilization of these resources by phytoplankton sets the biomass available to marine systems and is of particular interest in high-nutrient, low-chlorophyll (HNLC) coastal fisheries. Previous research has described the biogeography of phytoplankton in HNLC regions and the transcriptional responses of representative taxa to nutrient limitation. However, the differential transcriptional responses of whole phytoplankton communities to iron and nitrogen limitation has not been previously described, nor has the selective pressure that these competitive bloom environments exert on major players. In addition to describing changes in the physiology of diverse phytoplankton, we suggest practical indicators of cellular nitrogen and iron status for future monitoring.

Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol's effects.

Alcohol's impact on telomere length, a proposed marker of biological aging, is unclear. We performed the largest observational study to date (in n = 245,354 UK Biobank participants) and compared findings with Mendelian randomization (MR) estimates. Two-sample MR used data from 472,174 participants in a recent genome-wide association study (GWAS) of telomere length. Genetic variants were selected on the basis of associations with alcohol consumption (n = 941,280) and alcohol use disorder (AUD) (n = 57,564 cases). Non-linear MR employed UK Biobank individual data. MR analyses suggested a causal relationship between alcohol traits, more strongly for AUD, and telomere length. Higher genetically-predicted AUD (inverse variance-weighted (IVW) ß = -0.06, 95% confidence interval (CI): -0.10 to -0.02, p = 0.001) was associated with shorter telomere length. There was a weaker association with genetically-predicted alcoholic drinks weekly (IVW ß = -0.07, CI: -0.14 to -0.01, p = 0.03). Results were consistent across methods and independent from smoking. Non-linear analyses indicated a potential threshold relationship between alcohol and telomere length. Our findings indicate that alcohol consumption may shorten telomere length. There are implications for age-related diseases.