A tailored COVID-19 vaccination pathway for children 5-11 years in Victoria, Australia.

BACKGROUND: Procedural anxiety was anticipated in children 5-11 years during the COVID-19 vaccine rollout in Victoria, Australia, as children in this age group receive few routine vaccines. Therefore, the Victorian state government designed a tailored, child-friendly vaccine program. This study aimed to assess parental satisfaction with elements of the bespoke vaccination pathway. METHODS: The Victorian government and state-run vaccination hubs in Victoria facilitated an online immunisation plan to help parents identify their child's support needs, and utilised experienced paediatric staff and additional supports for children with severe needle distress and/or disability. All parents/guardians of children 5-11 years who received a COVID-19 vaccine in a vaccination hub were sent a 16-item feedback survey via text message. RESULTS: Between 9 February and 31 May 2022 there were 9203 responses; 865 children (9.4%) had a first language other than English, 499 (5.4%) had a disability or special needs, and 142 (1.5%) were Aboriginal or Torres Strait Islander. Most parents (94.4%; 8687/9203) rated their satisfaction with the program as very good or excellent. The immunisation plan was used by 13.5% (1244/9203) of respondents, with usage more common for Aboriginal or Torres Strait Islander children (26.1%; 23/88) or families with a first language other than English (23.5%; 42/179). The child-friendly staff (88.5%, 255/288) and themed environment (66.3%, 191/288) were the most valued measures for vaccination. Additional support measures were required by 1.6% (150/9203) of children in the general population and 7.9%, (17/261) of children with a disability and/or special needs. CONCLUSION: A tailored COVID-19 vaccination program for children 5-11 years, with additional support for children with severe needle distress and/or disability, had high parental satisfaction. This model could be utilised for COVID-19 vaccination in pre-school children and for routine childhood vaccination programs to provide optimal support to children and their families.

Distinct Mannheimia haemolytica serotypes isolated from fatal infections in veal calves and dairy cows.

Fatal Mannheimia haemolytica (M. haemolytica) infections in cattle, which emerged in the Netherlands between 2004 and 2018, showed two distinct disease presentations: acute fibrinous polyserositis (FPS) in veal calves, and acute fibrinous pleuro-pneumonia (FPP) in adult dairy cattle. To determine whether these presentations were caused by different M. haemolytica genotypes, whole genome sequencing was performed on 96 isolates cultured after necropsy from inflamed sites of veal calves that died of M. haemolytica-associated FPS (n = 49) or with FPP lesions (n = 2), and from dairy cows that died of M. haemolytica-associated FPP (n = 45). Among the 96 M. haemolytica isolates, 93 were shown to belong to either of two large clusters, with 48/51 calf isolates belonging to one, and 43/45 cow isolates and two calf isolates from cases of FPP to the other. All M. haemolytica isolates from veal calves with FPS were of serotype A2, whereas the isolates from dairy cows and two calves with FPP were predominantly of serotypes A1 and A6. Most serotype A2 isolates from veal calves with FPS (95.6 %) contained multiple antibiotic resistance genes (ARGs) against three to five antimicrobial classes (phenicols, sulphonamides, tetracyclines, aminoglycosides or beta-lactams). In contrast, these ARGs were only present in 10.8 % of M. haemolytica A1 and A6 isolates from pneumonic adult cattle and absent in isolates from the two calves with FPP. These two disease presentations appear to be caused by genetically distinct strains with different antimicrobial resistance gene patterns. While M. haemolytica serotype A2 is generally considered to be a commensal microorganism of cattle, it was clearly associated with fatal FPS in veal calves in the Netherlands.

MRI biomarker of muscle composition is associated with severity of pelvic organ prolapse.

BACKGROUND: The pathophysiology of pelvic organ prolapse is largely unknown. We hypothesized that reduced muscle mass on magnetic resonance defecography (MRD) is associated with increased pelvic floor laxity. The aim of this study was to compare the psoas and puborectalis muscle mass composition and cross-sectional area among patients with or without pelvic laxity. METHODS: An observational retrospective study was conducted on women > age 18 years old who had undergone MRD for pelvic floor complaints from January 2020 to December 2020 at Stanford Pelvic Health Center. Pelvic floor laxity, pelvic organ descent, and rectal prolapse were characterized by standard measurements on MRD and compared to the psoas (L4 level) and puborectalis muscle index (cross-sectional area adjusted by height) and relative fat fraction, quantified by utilizing a 2-point Dixon technique. Regression analysis was used to quantify the association between muscle characteristics and pelvic organ measurements. RESULTS: The psoas fat fraction was significantly elevated in patients with abnormally increased resting and strain H and M lines (p < 0.05) and increased with rising grades of Oxford rectal prolapse (p = 0.0001), uterovaginal descent (p = 0.001) and bladder descent (p = 0.0005). In multivariate regression analysis, adjusted for age and body mass index, the psoas fat fraction (not muscle index) was an independent risk factor for abnormal strain H and M line; odds ratio (95% confidence interval) of 17.8 (2-155.4) and 18.5 (1.3-258.3) respectively, and rising Oxford grade of rectal prolapse 153.9 (4.4-5383) and bladder descent 12.4 (1.5-106). Puborectalis fat fraction was increased by rising grades of Oxford rectal prolapse (p = 0.0002). CONCLUSIONS: Severity of pelvic organ prolapse appears to be associated with increasing psoas muscle fat fraction, a biomarker for reduced skeletal muscle mass. Future prospective research is needed to determine if sarcopenia may predict postsurgical outcomes after pelvic organ prolapse repair.

The association of ABO and Rhesus blood type with the risks of developing SARS-CoV-2 infection: A meta-analysis.

Coronavirus Disease 2019 (COVID-19) has been spreading like a wildfire everywhere in the globe. It has been challenging the global health care system ever since the end of 2019, with its virulence and pathogenicity. Recent studies have shown the association between ABO blood group, Rhesus blood type and susceptibility to COVID-19 infection. Various studies and few meta-analyses have been done and some might be inconsistent; therefore, this meta-analysis was done to assess the relationship between different ABO and Rhesus blood types on the susceptibility to COVID-19 infections. This meta-analysis assessed the odds ratio of COVID-19 infection of different ABO and Rhesus blood types. Subgroup analyses according to (1) age and gender matched; (2) different blood group antigens; (3) Rhesus positive and negative of each blood group were carried out. Publication bias and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were also done to assess the risk of bias in these publications. It was found that blood group A showed significant difference in odds ratio of COVID-19 infection (OR, 1.16; 95% CI, 1.08-1.24). Blood group AB showed significant difference in odds ratio when studies with lower QUADAS-2 score were removed. This means that populations with blood group A and AB are more likely to be infected with COVID-19. As there is a higher tendency that blood group A and AB to be infected with COVID- 19, precautious care should be taken by these populations.

The association of ABO and Rhesus blood type with the risks of developing SARS-CoV-2 infection: A meta-analysis

@#Coronavirus Disease 2019 (COVID-19) has been spreading like a wildfire everywhere in the globe. It has been challenging the global health care system ever since the end of 2019, with its virulence and pathogenicity. Recent studies have shown the association between ABO blood group, Rhesus blood type and susceptibility to COVID-19 infection. Various studies and few meta-analyses have been done and some might be inconsistent; therefore, this meta-analysis was done to assess the relationship between different ABO and Rhesus blood types on the susceptibility to COVID-19 infections. This meta-analysis assessed the odds ratio of COVID-19 infection of different ABO and Rhesus blood types. Subgroup analyses according to (1) age and gender matched; (2) different blood group antigens; (3) Rhesus positive and negative of each blood group were carried out. Publication bias and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were also done to assess the risk of bias in these publications. It was found that blood group A showed significant difference in odds ratio of COVID-19 infection (OR, 1.16; 95% CI, 1.08-1.24). Blood group AB showed significant difference in odds ratio when studies with lower QUADAS-2 score were removed. This means that populations with blood group A and AB are more likely to be infected with COVID-19. As there is a higher tendency that blood group A and AB to be infected with COVID19, precautious care should be taken by these populations.

Preventing transition "regret": An institutional ethnography of gender-affirming medical care assessment practices in Canada.

When a person openly "regrets" their gender transition or "detransitions" this bolsters within the medical community an impression that transgender and non-binary (trans) people require close scrutiny when seeking hormonal and surgical interventions. Despite the low prevalence of "regretful" patient experiences, and scant empirical research on "detransition", these rare transition outcomes profoundly organize the gender-affirming medical care enterprise. Informed by the tenets of institutional ethnography, we examined routine gender-affirming care clinical assessment practices in Canada. Between 2017 and 2018, we interviewed 11 clinicians, 2 administrators, and 9 trans patients (total n = 22), and reviewed 14 healthcare documents pertinent to gender-affirming care in Canada. Through our analysis, we uncovered pervasive regret prevention techniques, including requirements that trans patients undergo extensive psychosocial evaluations prior to transitioning. Clinicians leveraged psychiatric diagnoses as a proxy to predict transition regret, and in some cases delayed or denied medical treatments. We identified cases of patient dissatisfaction with surgical results, and a person who detransitioned. These accounts decouple transition regret and detransition, and no participants endorsed stricter clinical assessments. We traced the clinical work of preventing regret to cisnormativity and transnormativity in medicine which together construct regret as "life-ending", and in turn drives clinicians to apply strategies to mitigate the perceived risk of malpractice legal action when treating trans people, specifically. Yet, attempts to prevent these outcomes contrast with the material healthcare needs of trans people. We conclude that regret and detransitioning are unpredictable and unavoidable clinical phenomena, rarely appearing in "life-ending" forms. Critical research into the experiences of people who detransition is necessary to bolster comprehensive gender-affirming care that recognizes dynamic transition trajectories, and which can address clinicians' fears of legal action-cisgender anxieties projected onto trans patients who are seeking medical care.

Interobserver variability in the classification of childhood maculopapular cutaneous mastocytosis.

BACKGROUND: Maculopapular cutaneous mastocytosis (MPCM) in children is classified in two variants: (i) monomorphic variant, presenting with the small macules or papules typically seen in adult patients; and (ii) polymorphic variant with larger lesions of variable size and shape, typically seen in children. The definition of polymorphic and monomorphic variants is mostly intuitive, and a validation of this classification has not been done. OBJECTIVE: To study interobserver variability in the classification of MPCM in two groups of observers: mastocytosis experts and general dermatologists. MATERIALS AND METHODS: Nineteen cases of childhood MPCM were shown blindly, for classification as monomorphic or polymorphic type, to 10 independent observers (eight dermatologists, one allergist and one haematologist) from Europe and North America with a vast experience in the management of paediatric mastocytosis. Also, the same cases were shown on a screen to 129 general dermatologists attending a meeting; their votes were registered by remote controls. The interobserver variability kappa coefficient (with 95% confidence interval) was calculated to measure the reliability of the correlation. RESULTS: The value of kappa interobserver variability coefficient for the group of 10 experts (95% confidence interval) was 0.39 (0.18-0.63), which is considered as 'fair'. The value of kappa interobserver variability coefficient for the group of 129 general dermatologists (95% confidence interval) was 0.17 (0.06-0.39), which is considered as 'slight'. A complete agreement of all 10 experts was achieved in only four of 19 cases (21.1%) The most voted choice was concordant between the two groups in only 11 of the 19 cases. CONCLUSIONS: We failed to validate the classification system of childhood MPCM in monomorphic and polymorphic types. While the rate of agreement was low for mastocytosis experts, it was nearly the agreement expected by chance in general dermatologists.

A two-in-one Janus NIR-II AIEgen with balanced absorption and emission for image-guided precision surgery.

Fluorescence imaging in the near-infrared II (NIR-II, 1000-1700 nm) region opens up new avenues for biological systems due to suppressed scattering and low autofluorescence at longer-wavelength photons. Nonetheless, the development of organic NIR-II fluorophores is still limited mainly due to the shortage of efficient molecular design strategy. Herein, we propose an approach of designing Janus NIR-II fluorophores by introducing electronic donors with distinct properties into one molecule. As a proof-of-concept, fluorescent dye 2 TT-m, oC6B with both twisted and planar electronic donors displayed balanced absorption and emission which were absent in its parent compound. The key design strategy for Janus molecule is that it combines the merits of intense absorption from planar architecture and high fluorescence quantum yield from twisted motif. The resulting 2 TT-m, oC6B nanoparticles exhibit a high molar absorptivity of 1.12 ⨯104 M-1 cm-1 at 808 nm and a NIR-II quantum yield of 3.7%, displaying a typical aggregation-induced emission (AIE) attribute. The highly bright and stable 2 TT-m, oC6B nanoparticles assured NIR-II image-guided cancer surgery to resect submillimeter tumor nodules. The present study may inspire further development of molecular design philosophy for highly bright NIR-II fluorophores for biomedical applications.

A systematic review and meta-analysis of treatment-related toxicities of curative and palliative radiation therapy in non-small cell lung cancer.

Treatment-related toxicity is an important component in non-small cell lung cancer (NSCLC) management decision-making. Our aim was to evaluate and compare the toxicity rates of curative and palliative radiotherapy with and without chemotherapy. This meta-analysis provides better quantitative estimates of the toxicities compared to individual trials. A systematic review of randomised trials with > 50 unresectable NSCLC patients, treated with curative or palliative conventional radiotherapy (RT) with or without chemotherapy. Data was extracted for oesophagitis, pneumonitis, cardiac events, pulmonary fibrosis, myelopathy and neutropenia by any grade, grade ≥ 3 and treatment-related deaths. Mantel-Haenszel fixed-effect method was used to obtain pooled risk ratio. Forty-nine trials with 8609 evaluable patients were included. There was significantly less grade ≥ 3 acute oesophagitis (6.4 vs 22.2%, p < 0.0001) and any grade oesophagitis (70.4 vs 79.0%, p = 0.04) for sequential CRT compared to concurrent CRT, with no difference in pneumonitis (grade ≥ 3 or any grade), neutropenia (grade ≥ 3), cardiac events (grade ≥ 3) or treatment-related deaths. Although the rate of toxicity increased with intensification of treatment with RT, the only significant difference between treatment regimens was the rate of oesophagitis between the use of concurrent and sequential CRT. This can aid clinicians in radiotherapy decision making for NSCLC.

Potential role of fibroblast growth factor 21 in the deterioration of bone quality in impaired glucose tolerance.

PURPOSE: Findings on trabecular bone score (TBS), an index of bone quality, have been reported in prediabetes defined by impaired fasting glucose or HbA1c. Here, we assessed the bone mineral density (BMD) and TBS in prediabetes individuals with impaired glucose tolerance (IGT), and investigated the association of these bone parameters with serum levels of fibroblast growth factor 21 (FGF21), a hormone implicated in bone metabolism and with higher levels in IGT. METHODS: Chinese postmenopausal women aged 55-80 years, without diabetes, were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study in 2016-2018. Normal glucose tolerance (NGT) was defined by fasting glucose < 5.6 mmol/L and 2-h plasma glucose (2hG) < 7.8 mmol/L, and IGT by 2hG 7.8-11 mmol/L. Serum levels of FGF21 and other bone metabolism regulators were measured. Insulin sensitivity was assessed by the Matsuda index. Independent determinants of TBS were evaluated using multivariable stepwise linear regression. RESULTS: 173 individuals with NGT and 73 with IGT were included. TBS was lower in those with IGT compared to those with NGT, while BMD was comparable. Individuals with IGT had significantly higher serum FGF21 levels, which in turn showed an independent inverse relationship with TBS, attenuated after inclusion of the Matsuda index. Serum FGF21 levels, however, did not correlate with BMD. CONCLUSION: Among Chinese postmenopausal women, bone quality was worse in IGT, despite comparable bone density. FGF21 levels showed a significant independent inverse relationship with TBS, partly attributed to insulin resistance. Whether FGF21 contributes to the impaired bone quality in IGT remains speculative.

Colorectal stenting in England: a cross-sectional study of practice.

INTRODUCTION: UK and European guidelines recommend consideration of a self-expandable metallic stent (SEMS) as an alternative to emergency surgery in left-sided colonic obstruction. However, there is no clear consensus on stenting owing to concern for complications and long-term outcomes. Our study is the first to explore SEMS provision across England. METHODS: All colorectal surgery department leads in England were contacted in 2018 and invited to complete an objective multiple choice questionnaire pertaining to service provision of colorectal stenting (including referrals, time, location and specialty). RESULTS: Of 182 hospitals contacted, 79 responded (24 teaching hospitals, 55 district general hospitals). All hospitals considered stenting, with 92% performing stenting and the remainder referring. The majority (93%) performed fewer than four stenting procedures per month. Most (96%) stented during normal weekday hours, with only 25% stenting out of hours and 23% at weekends. Compared with district general hospitals, a higher proportion of teaching hospitals stented out of hours and at weekends. Stenting was performed in the radiology department (64%), the endoscopy department (44%) and operating theatres (15%), by surgeons (63%), radiologists (60%) and gastroenterologists (48%). A radiologist was present in 66% of cases. Of 14 hospitals that received referrals, 3 had a protocol, 3 returned patients the same day and 4 returned patients for management in the event of failure. CONCLUSIONS: All responding hospitals in England consider the use of SEMS in colonic obstruction. Nevertheless, there is great variation in stenting practices, and challenges in terms of access and expertise. Centralisation and regional referral networks may help maximise availability and expertise but more work is needed to support this.

Cytoreductive nephrectomy in metastatic renal cell carcinoma: outcome of patients treated with a multidisciplinary, algorithm-driven approach.

PURPOSE: Metastatic renal cell carcinoma (mRCC) represents a significant and rising burden of disease, with rapidly evolving treatment modalities. The role of cytoreductive nephrectomy (CN) is controversial in this setting. As such, London Cancer has pursued a multidisciplinary team (MDT) approach when assessing suitability for surgery. METHODS: A retrospective analysis of treatment-naive synchronous mRCC patients, managed via a renal-specialist MDT, was conducted between January 2015 and December 2018. An MDT selection algorithm for CN-using the International Metastatic Renal Cell Carcinoma Database Consortium score (IMDC), performance status and metastatic disease burden-was developed. RESULTS: 87 treatment-naive synchronous mRCC patients received either CN (n = 18), Systemic therapy (ST) alone (n = 43) or Best supportive care (BSC) (n = 26). Progression free survival (PFS) and overall survival (OS) were assessed. 51% and 39% were IMDC intermediate and poor risk. Median PFS was 28.6 months and 4.5 months in the CN group and ST alone group, respectively, Hazard Ratio for death was 3.63 [(95% CI 1.68-7.83) p < 0.05]. OS remains immature for the CN group, but a median OS of 12.8 months was observed in the ST group and 5.0 months for BSC. 1-year OS rate for CN, ST and BSC groups was 77.8%, 55.8% and 23.10%, respectively. CONCLUSION: These findings describe outcomes of an unselected series of patients treated via an MDT-driven, protocolised treatment pathway. MDT pathway-based decision making may improve patient selection for CN. Further research is needed to evaluate the role of CN amongst a growing landscape of treatment strategies, including immune checkpoint inhibitors and combination therapies. Multi-disciplinary team, pathway-based treatment strategy may improve patient selection for cytoreductive nephrectomy in patients with metastatic renal cell carcinoma.

Modular, tissue-specific, and biodegradable hydrogel cross-linkers for tissue engineering.

Synthetic hydrogels are investigated extensively in tissue engineering for their tunable physicochemical properties but are bioinert and lack the tissue-specific cues to produce appropriate biological responses. To introduce tissue-specific biochemical cues to these hydrogels, we have developed a modular hydrogel cross-linker, poly(glycolic acid)-poly(ethylene glycol)-poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT), that can be functionalized with small peptide-based cues and large macromolecular cues simply by mixing PdBT in water with the appropriate biomolecules at room temperature. Cartilage- and bone-specific PdBT macromers were generated by functionalization with a cartilage-associated hydrophobic N-cadherin peptide, a hydrophilic bone morphogenetic protein peptide, and a cartilage-derived glycosaminoglycan, chondroitin sulfate. These biofunctionalized PdBT macromers can spontaneously cross-link polymers such as poly(N-isopropylacrylamide) to produce rapidly cross-linking, highly swollen, cytocompatible, and hydrolytically degradable hydrogels suitable for mesenchymal stem cell encapsulation. These favorable properties, combined with PdBT's modular design and ease of functionalization, establish strong potential for its usage in tissue engineering applications.

Invasive paediatric Elizabethkingia meningoseptica infections are best treated with a combination of piperacillin/tazobactam and trimethoprim/sulfamethoxazole or fluoroquinolone.

OBJECTIVES: Elizabethkingia meningoseptica is a multi-drug-resistant organism that is associated with high mortality and morbidity in newborn and immunocompromised patients. This study aimed to identify the best antimicrobial therapy for treating this infection. METHODS: A retrospective descriptive study was conducted from 2010 to 2017 in a tertiary paediatric hospital in Singapore. Paediatric patients aged 0 to 18 years old with a positive culture for E. meningoseptica from any sterile site were identified from the hospital laboratory database. The data collected included clinical characteristics, antimicrobial susceptibility and treatment, and clinical outcomes. RESULTS: Thirteen cases were identified in this study. Combination therapy with piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluoroquinolone resulted in a cure rate of 81.8  %. The mortality rate was 15.4  % and neurological morbidity in patients with bacteraemia and meningitis remained high (75 %). CONCLUSIONS: Treatment with combination therapy of piperacillin/tazobactam and trimethoprim/sulfamethoxazole or a fluroquinolone was effective in this study, with low mortality rates being observed.

Canada's Prosthetic Coverage: a Review of Provincial Prosthetic Policy.

The Canadian healthcare system serves as an example of equity and federal service to citizens across the world. However, it is not without its challenges. Prosthetic coverage across Canada is highly variable and largely unable to provide equal coverage for Canadian persons living with amputation. Many persons with limb loss are forced to rely upon personal resources, fundraising, or the charity of non-governmental organizations in order to meet this basic healthcare need. This disparity in the Canadian healthcare system is unusual and largely undescribed in the literature. We thus explore the nature of Canadian healthcare prosthetic coverage across Canada, investigating the variability in coverage, presence of prosthetic coverage policies, clarity of policy, eligibility criteria, and interval of prosthetic replacement. Our findings highlight potential areas for improvement within current Canadian healthcare policy.