Clinical Characteristics of Gram-Negative Surgical Site Infections in Patients Treated With Mohs Micrographic Surgery: A Retrospective Analysis.

BACKGROUND: Surgical site infections (SSIs) are the most common adverse events after Mohs micrographic surgery (MMS). However, there is a paucity of literature characterizing gram-negative (GN) SSIs after MMS. OBJECTIVE: This study aimed to depict the clinical features and risk factors of GN infections after MMS. MATERIALS AND METHODS: A retrospective review was performed from all postoperative wound cultures after MMS from 2017 to 2021 at Saint Louis University Medical Center. Patient demographics, surgical details, and wound clinical characteristics at follow-up appointments were reviewed. RESULTS: Six hundred and seventy-six wound cultures were eligible with 15.1% yielding GN infection. Gram-negative SSIs had significantly lower rates of severe erythema and purulence compared with gram-positive (GP) SSIs, and only had significantly more edema compared with culture-negative wounds ( p < .05). Although not significant, there was a trend for GN SSIs to have higher rates of pain compared with culture-negative wounds ( p = .075). CONCLUSION: Gram-negative SSIs after MMS may present with more subtle clinical features, especially compared with typical GP infections. Having a low threshold for obtaining wound culture for edematous or painful postoperative wounds may aid in detecting potentially overlooked GN infections.

Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial.

BACKGROUND: Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT). METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY)control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130. FINDINGS: Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44-61) in the younger age group and 76 years (73-78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41-59) in the younger age group and 78 years (75-82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5-2·3) in the half VLA group to 32·3 (24·8-42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7-1·6) for ChAd to 3·6 (2·4-5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0-1·5) in the half VLA group to 11·5 (9·4-14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7-1·6) for half VLA to 4·7 (3·1-7·1) for m1273. The results were similar between those aged 30-69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30-69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273. INTERPRETATION: All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination. FUNDING: UK Vaccine Taskforce and National Institute for Health Research.

Characteristics of Lower Extremity Infection Rates Following Mohs Micrographic Surgery.

BACKGROUND: Surgical site infection (SSI) is the most common complication for Mohs micrographic surgery (MMS). Lower extremity surgical sites are at an increased risk for developing SSI. OBJECTIVE: This study aimed to evaluate lower extremity SSI rates post-MMS based on closure type and antibiotic usage. MATERIALS AND METHODS: A retrospective review was performed of all lower extremity MMS cases from 2011 to 2016 at Vanderbilt University Medical Center. Patient history, surgical details, and follow-up appointments were reviewed. RESULTS: Six hundred twenty MMS lower extremity surgeries were eligible. Review identified an overall lower extremity SSI rate of 7.4%. Infection rates were significantly increased in wound closed by flaps/grafts (p < .001). Although wound size and preoperative antibiotic prophylaxis were initially associated with increased infection rate (p = .03, p = .015), the associations were fully attenuated when adjusting for closure type. CONCLUSION: More complicated repair techniques (flap/graft) for larger wound sizes contribute to increased SSI risk among lower extremity MMS cases. Providers can use this information to guide antibiotic prophylaxis.

Bannayan-Riley-Ruvalcaba syndrome with gingival hyperpigmentation and facial papules.

One of the distinctive cutaneous manifestations of Bannayan-Riley-Ruvalcaba syndrome (BRRS), a PTEN hamartoma tumor syndrome, is penile pigmented macules. We present a 13-year-old boy with gingival hyperpigmentation along with facial and ear angiofibromas in the context of a BRRS-concordant phenotype and PTEN hamartoma tumor syndrome genotype. To our knowledge, these two findings have not been previously reported with BRRS and may expand the known phenotype of this disorder.

Identification of quinazoline based inhibitors of IRAK4 for the treatment of inflammation.

Interleukin-1 receptor associated kinase 4 (IRAK4) has been implicated in IL-1R and TLR based signaling. Therefore selective inhibition of the kinase activity of this protein represents an attractive target for the treatment of inflammatory diseases. Medicinal chemistry optimization of high throughput screening (HTS) hits with the help of structure based drug design led to the identification of orally-bioavailable quinazoline based IRAK4 inhibitors with excellent pharmacokinetic profile and kinase selectivity. These highly selective IRAK4 compounds show activity in vivo via oral dosing in a TLR7 driven model of inflammation.

Bullous Pemphigoid: Use of C4d Immunofluorescent Staining in a Case With Repeated Negative Conventional Direct Immunofluorescence Studies.

Direct immunofluorescence (DIF) using frozen section material from a fresh/preserved perilesional biopsy is the gold standard for the immunopathologic diagnosis of bullous pemphigoid (BP). DIF in BP shows linear dermoepidermal junction (DEJ) staining for C3, with or without staining for IgG. In some situations, only a formalin-fixed lesional biopsy is obtained (with no fresh/preserved perilesional biopsy for DIF). In this setting, paraffin section C4d immunohistochemistry has proven to be diagnostically useful, demonstrating linear DEJ positivity for C4d. We present a novel use of C4d staining for the diagnosis of BP, specifically analyzing C4d perilesional frozen section DIF in a case where standard perilesional frozen section DIF for IgG/C3 was available, but was negative. An 80-year-old woman presented with a pruritic bullous lesion on her left upper extremity, clinically thought to represent BP. Lesional histologic findings were typical for BP, but perilesional frozen section DIF staining was negative for IgG and C3. A second set of biopsies processed at a different laboratory yielded the same result. A diagnosis of bullous scabies was considered. Subsequently, perilesional frozen section DIF for C4d was obtained, which showed strong linear DEJ positivity, confirming the diagnosis of BP. DIF for C4d is widely used in transplant pathology, since C4d is persistent in tissue, versus C3. Our case demonstrates that perilesional frozen section DIF staining for C4d may be positive and diagnostic in BP, even when conventional DIF staining for IgG and C3 is negative.

A Report of a Keratoacanthoma-Type Cutaneous Squamous Cell Carcinoma Arising Within a Multicolored Ink Tattoo.

Keratoacanthoma (KA) is a common, low-grade, rapidly growing cutaneous squamous cell carcinoma that presents as an enlarging crateriform nodule, which may spontaneously involute but rarely metastasizes. Immunosuppression, ultraviolet light, viral infection, surgical procedures, and trauma are associated with their development. Overall, tattoo-induced squamous cell neoplasms are infrequently described in the literature. Carcinogenesis is hypothesized to result from trauma caused by the tattooing procedure or a foreign body reaction to the pigment. However, the pathogenesis has not been clearly defined. While most commonly associated with red ink, to date, very few cases of KA forming within black, blue, or multicolored ink tattoos are reported. Herein, we describe a case of KA arising within areas of blue and black pigment in a decorative ink tattoo.

A systematic review of methods of scoring inhaler technique.

Many inhaler devices are currently used in clinical practice to deliver medication, with each inhaler device offering different benefits to overcome technique issues. Inhaler technique remains poor, contributing to reduced airway drug deposition and consequently poor disease control. Scoring inhaler technique has been used within research as an outcome measure of inhaler technique assessment, and this systematic review collates and evaluates these scoring methods. The review protocol was prospectively registered in PROSPERO (CRD42020218869). A total of 172 articles were screened with 77 included, and the results presented using narrative synthesis due to the heterogeneity of the study design and data. The most frequently used scoring method awarded one point per step in the inhaler technique checklist and was included in 59/77 (77%) of articles; however limited and varied guidance was provided for score interpretation. Other inhaler technique scoring methods included grading the final inhaler technique score, expressing the total score as a percentage/ratio, deducting points from the final score when errors were made, and weighting steps within the checklist depending on how crucial the step was. Vast heterogeneity in the number of steps and content in the inhaler technique checklists was observed across all device types (range 5-19 steps). Only 4/77 (5%) of the inhaler technique measures had undertaken fundamental steps required in the scale development process for use in real world practice. This review demonstrates the demand for a tool that measures inhaler technique and highlights the current unmet need for one that has undergone validation.

Persistence of immune responses after heterologous and homologous third COVID-19 vaccine dose schedules in the UK: eight-month analyses of the COV-BOOST trial.

BACKGROUND: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave. This report compares the immunogenicity and kinetics of responses to third doses of vaccines from day (D) 28 to D242 following third doses in seven study arms. METHODS: The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) delivered at three groups of six sites. Participants in each site group were randomised to three or four experimental vaccines, or MenACWY control. The trial was stratified such that half of participants had previously received two primary doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) and half had received two doses of BNT162b2 (Pfizer-BioNtech, hereafter referred to as BNT). The D242 follow-up was done in seven arms (five full-dose, two half-dose). The BNT vaccine was used as the reference as it was the most commonly deployed third-dose vaccine in clinical practice in high-income countries. The primary analysis was conducted using all randomised and baseline seronegative participants who were SARS-CoV-2 naïve during the study and who had not received a further COVID-19 vaccine for any reason since third dose randomisation. RESULTS: Among the 817 participants included in this report, the median age was 72 years (IQR: 55-78) with 50.7% being female. The decay rates of anti-spike IgG between vaccines are different among both populations who received initial doses of ChAd/ChAd and BNT/BNT. In the population that previously received ChAd/ChAd, mRNA vaccines had the highest titre at D242 following their vaccine dose although Ad26. COV2. S (Janssen; hereafter referred to as Ad26) showed slower decay. For people who received BNT/BNT as their initial doses, a slower decay was also seen in the Ad26 and ChAd arms. The anti-spike IgG became significantly higher in the Ad26 arm compared to the BNT arm as early as 3 months following vaccination. Similar decay rates were seen between BNT and half-BNT; the geometric mean ratios ranged from 0.76 to 0.94 at different time points. The difference in decay rates between vaccines was similar for wild-type live virus-neutralising antibodies and that seen for anti-spike IgG. For cellular responses, the persistence was similar between study arms. CONCLUSIONS: Heterologous third doses with viral vector vaccines following two doses of mRNA achieve more durable humoral responses compared with three doses of mRNA vaccines. Lower doses of mRNA vaccines could be considered for future booster campaigns.

Efficacy outcomes and prognostic factors from real-world patients with advanced non-small-cell lung cancer treated with first-line chemoimmunotherapy: The Spinnaker retrospective study.

BACKGROUND: Efficacy outcomes and prognostic factors of real-world patients with advanced non-small cell lung cancer (aNSCLC) treated with first-line chemoimmunotherapy are still limited. PATIENTS AND METHODS: In the retrospective Spinnaker study, data was collected from patients in six United Kingdom and one Swiss oncology centres with first-line pembrolizumab plus platinum-based chemotherapy. Efficacy outcomes and potential prognostic factors were estimated aiming at developing a prognostic model. RESULTS: Three-hundred-eight patients were included, 32% ≥ 70 years, with ≥ 3 metastatic sites in 33%, brain or liver metastases in 10% and 12%, respectively. With a median follow-up of 18.0 months (mo.) (range, 15.9-20.1), median overall survival (OS) and progression-free survival (PFS) were 12.7 mo. (range, 10.2-15.2), and 8.0 mo. (range, 7.1-8.8), respectively. The neutrophils-to-lymphocytes ratio (NLR) and systemic immune-inflammatory index (SII) (i.e., NLR × platelet count) were both significantly higher in ECOG PS 1 (p = 0.0147 and p = 0.0018, respectively), underweight or normal body mass index (p = 0.0456 and p = 0.0062, respectively), ≥3 metastatic sites (p = 0.0069 and p = 0.112), pretreatment steroids (p = 0.0019 and p = 0.0017). By MVA, the number of metastatic sites ≥ 3 (p < 0.001 and p = 0.002), squamous histology (p = 0.033 and p = 0.013) and SII ≥ 1444 (p = 0.031 and p = 0.009, respectively) were associated with both worse OS and PFS and led to a highly discriminating three-class risk prognostic model. CONCLUSION: Real-world PFS with chemoimmunotherapy in aNSCLC patients is similar to that reported in clinical trials. A high number of metastatic sites, squamous histology and high SII are adverse prognostic factors that might contribute to a clinically useful prognostic model.

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial.

BACKGROUND: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. METHODS: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. FINDINGS: Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57-0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. INTERPRETATION: Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19. FUNDING: Sponsored by the University of Dundee and supported through an Investigator Initiated Research award from Insmed, Bridgewater, NJ; STOP-COVID19 trial.

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial.

BACKGROUND: Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19. METHODS: The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (anti-spike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing. FINDINGS: Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6-77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3-214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030-27 162), which increased to 37 460 ELU/mL (31 996-43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41-1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996-30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826-64 452), with a geometric mean fold change of 2·19 (1·90-2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37-14·32) and 15·90 (12·92-19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24-16·54] in the BNT162b2 group and 6·22 [3·90-9·92] in the mRNA-1273 group). INTERPRETATION: Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose. FUNDING: UK Vaccine Task Force and National Institute for Health Research.

Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial.

OBJECTIVES: To evaluate the persistence of immunogenicity three months after third dose boosters. METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. RESULTS: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 µg) or BNT (30 µg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 µg) versus BNT (30 µg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. CONCLUSIONS: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.

The use of aerosol generating procedures (AGPs) during the COVID-19 pandemic in the diagnosis of lung cancer: a narrative review.

OBJECTIVE: In this article we discuss the current evidence for these concerns and highlight where further work is required to understand the risk from these procedures and how it can be mitigated for. BACKGROUND: The COVID-19 (coronavirus-19 or SARS-CoV-2) pandemic has impacted on many aspects of patient care both for those with the virus and those with other illnesses. Of particular concern has been the risk to staff and patients from the spread of the virus in health care settings. This has led to changes in guidelines and practice in community and hospital settings that has implications on patient diagnostic pathways in lung cancer, with a specific emphasis on aerosol generating procedures (AGPs). METHODS: A literature search was carried out and 44 abstracts were initially found. Given the novel status of COVID-19, we included severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in our search. Five papers were selected for further analysis. An additional paper was highlighted during our research and therefore included in our review. CONCLUSIONS: The papers selected assessed the risk of transmission during AGPs. The six articles selected assessed the risk of aerosol transmission during various AGPs (bronchoscopy, pleural procedures and pulmonary function tests) and each found that the risk of viral transmission via aerosol was low. As mentioned above, at the time the paper was written, there was a paucity of evidence regarding AGPs in the era of COVID-19. There is emerging evidence that our understanding of these procedures may be outdated and the risk of transmission maybe lower than previously anticipated. However, we need further reliable evidence to change practice going forward.

The VICTORY (Investigation of Inflammacheck to Measure Exhaled Breath Condensate Hydrogen Peroxide in Respiratory Conditions) Study: Protocol for a Cross-sectional Observational Study.

BACKGROUND: More than 7% of the world's population is living with a chronic respiratory condition. In the United Kingdom, lung disease affects approximately 1 in 5 people, resulting in over 700,000 hospital admissions each year. People with respiratory conditions have several symptoms and can require multiple health care visits and investigations before a diagnosis is made. The tests available can be difficult to perform, especially if a person is symptomatic, leading to poor quality results. A new, easy-to-perform, point-of-care test that can be performed in any health care setting and that can differentiate between various respiratory conditions would have a significant, beneficial impact on the ability to diagnose respiratory diseases. OBJECTIVE: The objective of this study is to use a new handheld device (Inflammacheck) in different respiratory conditions to measure the exhaled breath condensate hydrogen peroxide (EBC H2O2) and compare these results with those of healthy controls and with each other. This study also aims to determine whether the device can measure other parameters, including breath humidity, breath temperature, breath flow dynamics, and end tidal carbon dioxide. METHODS: We will perform a single-visit, cross-sectional observational study of EBC H2O2 levels, as measured by Inflammacheck, in people with respiratory disease and volunteers with no known lung disease. Participants with a confirmed diagnosis of asthma, chronic obstructive pulmonary disease, lung cancer, bronchiectasis, pneumonia, breathing pattern disorder, and interstitial lung disease as well as volunteers with no history of lung disease will be asked to breathe into the Inflammacheck device to record their breath sample. RESULTS: The results from this study will be available in 2022, in anticipation of COVID-19-related delays. CONCLUSIONS: This study will investigate the EBC H2O2, as well as other exhaled breath parameters, for use as a future diagnostic tool.

A Study to Investigate the Prevalence of Device-Specific Errors in Inhaler Technique in Adults With Airway Disease (The SCORES Study): Protocol for a Single Visit Prevalence Study.

BACKGROUND: It is a recurring theme in clinical practice that patients using inhaled medications via an inhaler do not use their device to a standard that allows for optimum therapeutic effect, and some studies have shown that up to 90% of people do not use their inhalers properly. Observation and correction of the inhaler technique by health care professionals is advised by both national and international guidelines and should be performed at every opportunity to ensure that the optimum inhaler technique is achieved by the user. This study will provide a greater understanding of the most frequent technique errors made by people using 13 different inhaler types. OBJECTIVE: This study aims to identify and compare inhaler technique errors and their prevalence in adults, using device-specific checklists in accordance with manufacturers' guidelines, for 13 specific inhaler types across all lung conditions and to correlate these errors with possible determinants of poor technique. It also aims to assess the error frequency at each step in the device-specific questionnaires and compare the error rates among device types. METHODS: In a single visit, participants using an inhaler included in the inclusion criteria will have their inhaler technique observed using an identical placebo device, which will be recorded using device-specific checklists, and technique-optimized, or switched to a suitable inhaler. RESULTS: The study is already underway, and it is anticipated that the results will be available by 2022. CONCLUSIONS: The SCORES (Study to Investigate the Prevalence of Device-Specific Errors in Inhaler Technique in Adults With Airway Disease) study will ascertain the prevalence of device-specific inhaler technique errors at each step in the device-specific checklists, compare error rates among 13 device types, and correlate these errors with possible determinants of poor technique. Future work will involve the clarification and classification of these errors into critical and noncritical categories. TRIAL REGISTRATION: ClinicalTrials.gov NCT04262271; https://clinicaltrials.gov/ct2/show/NCT04262271. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26350.

Specialist respiratory outreach: a case-finding initiative for identifying undiagnosed COPD in primary care.

COPD remains largely undiagnosed or is diagnosed late in the course of disease. We report findings of a specialist outreach programme to identify undiagnosed COPD in primary care. An electronic case-finding algorithm identified 1602 at-risk patients from 12 practices who were invited to attend the clinic. Three hundred and eighty-three (23.9%) responded and 288 were enrolled into the study. Forty-eight (16.6%) had undiagnosed mild and 28 (9.7%) had moderate airway obstruction, meeting spirometric diagnostic criteria for COPD. However, at 12 months only 8 suspected COPD patients (10.6%) had received a diagnostic label in their primary care record. This constituted 0.38% of the total patient population, as compared with 0.31% of control practices, p = 0.306. However, if all patients with airway obstruction received a coding of COPD, then the diagnosis rate in the intervention group would have risen by 0.84%. Despite the low take-up and diagnostic yield, this programme suggests that integrated case-finding strategies could improve COPD recognition.

What's eating you? clinical manifestations of Dermacentor tick bites.

Dermacentor ticks are hard ticks found throughout most of North America and are easily identified by their large size, ornate scutum, and prominent dorsal pits. They are important disease vectors and are implicated in transmission of Rocky Mountain spotted fever (RMSF), Colorado tick fever, tularemia, and erlichiosis. They also are an important cause of fatal tick paralysis.

A time for everything and everything in its time - exploring the mechanisms underlying seasonality of COPD exacerbations.

Across Europe, COPD affects 23 million people leading to annual health care costs of ~€25.1 billion. This burden is particularly severe during winter months in association with the peak incidence of exacerbation events. Seasonal variation in the health status of patients with COPD places additional and often critical pressure on already strained health care resources. COPD exacerbations are characterized by worsening day-to-day symptoms of an individual and often triggered by respiratory infections, but the process by which this occurs in a seasonal fashion is likely to be multifactorial. In this review, we discuss recent population studies that highlight the impact of seasonality in COPD and review the proposed biological mechanisms underlying this. An appraisal of the role of the host susceptibility and response, environmental triggers and the biology of respiratory pathogens is detailed. The impact of each aspect is considered, and an integrated model of the context for the whole individual and society in general is explored.