Indications and Short-Term Outcomes for In-Office Therapeutic Superior Laryngeal Nerve Block.

OBJECTIVE: Superior laryngeal nerve (SLN) block consists of injection of steroid and anesthetic at the internal branch of the SLN entry site. Prior case series have demonstrated beneficial effects on neurogenic cough. SLN blocks have also recently shown benefit for paralaryngeal pain. We describe short-term outcomes for multiple symptoms of irritable larynx syndrome (ILS) including neurogenic cough, dysphonia related to laryngeal hypersensitivity, inducible laryngeal obstruction (ILO), paralaryngeal pain, and isolated globus. METHODS: Retrospective review from 2 institutions of patients undergoing a single SLN block for the indications listed. Variables include age, sex, indication(s), known vagus neuropathy, and patient-reported outcomes at short-term follow-up. RESULTS: A total of 209 patients were included (59 males, 150 females; age: 58 ± 13 years). Twenty-six patients (12%) had a history of a vagus nerve injury. Indications included neurogenic cough (n = 149), dysphonia related to laryngeal hypersensitivity (n = 66), paralaryngeal pain (n = 50), ILO (n = 23), and isolated globus (n = 3). Some patients had multiple indications. Significant improvements in patient-reported measures occurred after a single SLN block within 2 to 4 weeks for neurogenic cough (cough severity index; 25.2 ± 11.2 to 19.0 ± 12.8; P < .001), dysphonia (voice handicap index-10; 22.1 ± 12.2-18.0 ± 13.3; P = .005), and ILO (dyspnea index; 21.0 ± 14.9-14.7 ± 15.7; P = .017). Subjective pain improved in 23 of 39 patients with paralaryngeal pain. There was no observed improvement for isolated globus. Presence of known vagal neuropathy or therapy around the time of SLN block did not affect outcome. CONCLUSION: SLN block can be an effective component of treatment for a variety of ILS symptoms. Patients may experience some improvement after 1 injection. LAY SUMMARY: Symptoms of irritable larynx syndrome, such as neurogenic cough, paralaryngeal pain, inducible laryngeal obstruction, and dysphonia related to laryngeal hypersensitivity can be challenging to manage. In-office Superior Laryngeal Nerve blocks can serve as a quick, well tolerated, adjunctive treatment with positive short-term outcomes. LEVEL OF EVIDENCE: 4.

AMPK and PGC-α following maximal and supramaximal exercise in men and women: a randomized cross-over study.

We tested the hypothesis that AMPK activation and peroxisome proliferator gamma coactivator 1 alpha (PGC-1α) expression are not augmented as exercise intensity (power output) increases from maximal to supramaximal intensities and conducted an exploratory analysis comparing AMPK activation and PGC-1α expression in males and females. Seventeen (n = 9 males; n = 8 females) recreationally active, healthy, young individuals volunteered to participate in the current study. Participants completed work matched interval exercise at 100% (Max) and 133% (Supra) of peak work rate (WRpeak). Intervals were 1 min in duration and participants were prescribed 6 and 8 intervals of Max and Supra, respectively, to equate external work across protocols. PGC-1α mRNA expression and activation of AMPK (p-ACC) were examined in muscle biopsy samples. Interval WR (watts; W), intensity (%WRpeak) and average HR (bpm), blood lactate (mmol/L) and rating of perceived exertion were all higher (all p < 0.05) in Supra. Fatigue was greater (p < 0.05) in Supra. PGC-1α mRNA expression significantly increased after exercise in Max (p < 0.01) and Supra (p < 0.01), but was not significantly different (p = 0.71) between intensities. A main effect of time (Pre - 0 h) (p < 0.01) was observed for p-ACC; however, no effect of intensity (p = 0.08) or interaction (p = 0.97) was observed. No significant effects of time (p = 0.05) intensity (p = 0.42), or interaction (p = 0.97) were observed for p-AMPK (Thr172). Exploratory sex analysis demonstrated a main effect of sex for p-ACC (greater p-ACC in males; p < 0.05) but not for p-AMPK or PGC-1α expression. Our results confirm that AMPK-PGC-1α signalling is not augmented following supramaximal exercise and provide novel data demonstrating a decrease in AMPK activation (p-ACC) in females compared to men. Trial registration: https://doi.org/10.17605/OSF.IO/U7PX9.

Vocal Fold Polyps: A Scoping Review.

OBJECTIVE: This review aims to summarize the current understanding of vocal fold polyp etiology, pathophysiology, and prognosis, as well as recent developments in management. STUDY DESIGN: Scoping literature review. REVIEW METHODS: OVID Medline, PubMed, Google Scholar, Conference Papers Index, and Cochrane Library were searched for publications within the last 5 years using terms including "vocal," "cord," "fold," and "polyp." All abstracts were screened. Relevant studies pertaining to the etiology, pathophysiology, diagnosis, management, and prognosis of vocal fold polyps (VFPs) were included for review. RESULTS: Eight-hundred and sixty-five citations resulted from database review. Seven-hundred and thirty citations remained after the exclusion of duplicates. One hundred and ninety-three papers underwent abstract review, with 73 citations undergoing full-text review. Fifty-nine papers were included in the review. CONCLUSIONS: VFPs are one of the most common subtypes of benign vocal fold lesions. Phonotrauma contributes significantly to the development of these lesions, with laryngopharyngeal reflux and smoking also contributing. Correct diagnosis relies on a careful history, stroboscopy, response to voice therapy, and, in some cases, intraoperative findings. Phonosurgery is a definitive means of treatment, though more recently, in-office procedures have demonstrated efficacy and are potentially less costly and less invasive treatment options. Treatment modalities can be tailored based on the type and size of the lesion, the patient's vocal needs, medical comorbidities, and initial response to voice therapy. Voice specialists can anticipate greater emphasis placed on minimally invasive office-based procedures for the management of vocal pathology.

Membranous Vocal Fold Lesions in Patients With Chronic Cough: A Case Series.

OBJECTIVES: Trauma related to chronic cough and forceful glottal closure has been associated with lesions of the vocal process; however, there is limited description of cough leading to membranous vocal fold lesions. We present a series of mid-membranous vocal fold lesions in a cohort of patients with chronic cough, with a proposed mechanism of lesion formation. METHODS: Patients treated for chronic cough with membranous vocal fold lesions affecting phonation were identified. Presentation, diagnosis, treatment strategies (behavioral, medical, and surgical), patient-reported outcome measures (PROMs), and videostroboscopy were reviewed. RESULTS: Five patients are included (four females, one male, aged 56±16 years). Mean cough duration was 2.6±3.5 years. All patients were on acid suppressive medications for existing gastroesophageal reflux disease (GERD) prior to referral. All lesions were identified at the mid-membranous vocal folds and morphologically encompassed a wound healing spectrum between ulceration and/or granulation tissue (granuloma) formation. Patients were treated in an interdisciplinary fashion with behavioral cough suppression therapy, superior laryngeal nerve block, and neuromodulators. Three had persistent lesions requiring procedural intervention (one office-based steroid injection and two surgical excisions). At the completion of treatment, all five patients had improvement in Cough Severity Index with an average decrease of 15.2±4.8. All but one patient had improvement in their Voice Handicap Index-10 with an average decrease of 13.2±11.1. One patient undergoing surgical intervention was noted to have a persistent lesion on follow-up. CONCLUSION: Mid-membranous vocal fold lesions in patients with chronic cough are uncommon. When they do occur, they represent epithelial change arising in context of shear injury and are distinct from phonotraumatic lesions in the lamina propria. An interdisciplinary approach including behavioral cough suppression therapy, neuromodulators, superior laryngeal nerve block, and acid suppression are reasonable for initial management, reserving surgical intervention for refractory lesions once the inciting source of injury has been controlled.

Measurement and assessment of grief in a large international sample.

BACKGROUND: In 2022, the International Classification of Diseases (ICD-11) and an update of the Diagnostic Statistical Manual of Mental Disorders (DSM 5 TR) were released for implementation worldwide and now include the new Prolonged Grief Disorder (PGD). The newest definition of PGD is based on robust clinical research from the Global North yet until now has not been tested for global applicability. METHODS: The current study assesses the new PGD ICD-11 criteria in a large international sample of 1393 bereaved adults. The majority of the sample was included from the USΑ. Additionally, we conduct a sub-sample analysis to evaluate the psychometric properties, probable caseness of PGD, and differences in network structure across three regions of residency (USA, Greece-Cyprus, Turkey-Iran). RESULTS: The psychometric validity and reliability of the 33-item International Prolonged Grief Disorder Scale (IPGDS) were confirmed across the whole sample and for each regional group. Using the strict diagnostic algorithm, the probable caseness for PGD for the whole sample was 3.6 %. Probable caseness was highest for the Greece-Cyprus group (6.9 %) followed by Turkey-Iran (3.2 %) and the USA (2.8 %). Finally, the network structure of the IPGDS standard items and cultural supplement items (total of 33 items) confirmed the strong connection between central items of PGD, and revealed unique network connections within the regional groups. LIMITATIONS: Future research is encouraged to include larger sample sizes and a more systematic assessment of culture. CONCLUSION: Overall, our findings confirm the global applicability of the new ICD-11 PGD disorder definition as evaluated through the newly developed IPGDS. This scale includes culturally sensitive grief symptoms that may improve clinical precision and decision-making.

Associations Between Primary Residence and Mental Health in Global Marginalized Populations.

Scholars suggest that marginalized people in non-urban areas experience higher distress levels and fewer psychosocial resources than in urban areas. Researchers have yet to test whether precise proximity to urban centers is associated with mental health for marginalized populations. We recruited 1733 people who reported living in 45 different countries. Participants entered their home locations and completed measures of anxiety, depression, social support, and resilience. Regression and thematic analyses were used to determine what role distance from legislative and urban centers may play in mental health when marginalized people were disaggregated. Greater distance from legislative center predicted higher anxiety and resilience. Greater distance from urban center also predicted more resilience. Thematic analyses yielded five categories (e.g., safety, connection) that further illustrated the impact of geographic location on health. Implications for community mental health are discussed including the need to better understand and further expand resilience in rural areas.

The Impact of Parental Presence Restrictions on Canadian Parents in the NICU During COVID-19: A National Survey.

The purpose of this research was to explore parental perspectives on the impact of parent restrictions imposed in response to the COVID-19 pandemic across Canadian Neonatal Intensive Care Units (NICUs). A co-designed online survey was conducted targeting parents (n = 235) of infants admitted to a Canadian NICU from March 1, 2020, until March 5, 2021. Parents completed the survey from 38 Canadian NICUs. Large variation in the severity of policies regarding parental presence was reported. Most respondents (68.9%) were classified as experiencing high restrictions, with one or no support people allowed in the NICU, and felt that policies were less easy to understand, felt less valued and respected, and found it more challenging to access medicine or health care. Parents reported gaps in care related to self-care, accessibility, and mental health outcomes. There is significant variation in parental restrictions implemented across Canadian NICUs. National guidelines are needed to support consistent and equitable care practices.

Neurodevelopmental outcomes of very preterm infants who received cord milking at birth: a randomized controlled trial.

Umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. Little is known about the impact of umbilical cord milking on long-term neurodevelopmental outcomes. The objective of this study is to compare the effects of intact umbilical cord milking (UCM) vs. early cord clamping (ECC) at birth on neurodevelopmental outcomes at 36 months' corrected age. Preterm infants < 31 weeks' gestation who were randomized at birth to receive three time milking of their attached cord or ECC (< 10 s) were evaluated at 36 months' corrected age. Neurodevelopmental outcomes were assessed by blinded examiners using Bayley Scales of Infant and Toddler Development (version III). Analysis was by intention to treat. Out of the 73 infants included in the original trial, 2 died and 65 (92%) infants were evaluated at 36 months' corrected age. Patient characteristics and short-term outcomes were similar in both study groups. There were no significant differences in the median cognitive, motor or language scores or in the rates of cerebral palsy, developmental impairment, deafness, or blindness between study groups. CONCLUSION: Neurodevelopmental outcomes at 36 months' corrected age of very preterm infants who received UCM were not shown to be significantly different from those who received ECC at birth. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01487187 What is Known: • Compared to early cord clamping, umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. • Little is known about the impact of umbilical cord milking on neurodevelopmental outcomes. WHAT IS NEW: • Neurodevelopmental outcomes at 3 years of age were not significantly different in very preterm infants who received cord milking vs. those who received early cord clamping at birth.

A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia.

The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (ß-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.

Evidence of horizontal urban heat advection in London using six years of data from a citizen weather station network.

Recent advances in citizen weather station (CWS) networks, with data accessible via crowd-sourcing, provide relevant climatic information to urban scientists and decision makers. In particular, CWS can provide long-term measurements of urban heat and valuable information on spatio-temporal heterogeneity related to horizontal heat advection. In this study, we make the first compilation of a quasi-climatologic dataset covering six years (2015-2020) of hourly near-surface air temperature measurements obtained via 1560 suitable CWS in a domain covering south-east England and Greater London. We investigated the spatio-temporal distribution of urban heat and the influences of local environments on climate, captured by CWS through the scope of Local Climate Zones (LCZ)-a land-use land-cover classification specifically designed for urban climate studies. We further calculate, for the first time, the amount of advected heat captured by CWS located in Greater London and the wider south east England region. We find that London is on average warmer by about 1.0 ∘C-1.5 ∘C than the rest of south-east England. Characteristics of the southern coastal climate are also captured in the analysis. We find that on average, urban heat advection (UHA) contributes to 0.22 ± 0.96 ∘C of the total urban heat in Greater London. Certain areas, mostly in the centre of London are deprived of urban heat through advection since heat is transferred more to downwind suburban areas. UHA can positively contribute to urban heat by up to 1.57 ∘C, on average and negatively by down to -1.21 ∘C. Our results also show an important degree of inter- and intra-LCZ variability in UHA, calling for more research in the future. Nevertheless, we already find that UHA can impact green areas and reduce their cooling benefit. Such outcomes show the added value of CWS when considering future urban design.

In-Office Superior Laryngeal Nerve Block for Paralaryngeal Pain and Odynophonia.

OBJECTIVES: Pain localized to the thyrohyoid region may be due to neuralgia of the superior laryngeal nerve (SLN), inflammation of the thyrohyoid complex, or a voice disorder. We present outcomes of treatment of paralaryngeal pain and odynophonia with SLN block. STUDY DESIGN: Retrospective Review. METHODS: A retrospective chart review of patients undergoing in-office SLN block for paralaryngeal pain between 2015 and 2018 at two tertiary care centers was conducted. Patient demographics, indications, and response to treatment were analyzed. RESULTS: Thirty-eight patients underwent blockade of the internal branch of the SLN for paralaryngeal pain, with 10 excluded for incomplete medical records. Eighty-two percent (23/28) reported an improvement in their symptoms. Patients underwent an average of 2.5 blocks (SD = 1.88, range 1-8), with 10 patients (36%) undergoing a single procedure. Of the 18 patients who underwent multiple blocks, nine had eventual cessation of symptoms (50%) compared to resolution in 6/10 undergoing a single injection. Eleven patients (39%) noted odynophonia related to vocal effort, and all of these patients had improvement in or resolution of their symptoms and were more likely to improve compared to those without odynophonia (P = .006). Of the four patients who had a vocal process granuloma (VPG) at presentation, three had complete resolution of the lesion at follow-up. CONCLUSION: In-office SLN block is effective in the treatment of paralaryngeal pain. It may be used as an adjunct in the treatment of vocal process granulomas, as well as voice disorders where odynophonia is a prominent symptom. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:401-405, 2022.

Twenty-One for 2021: The Most Influential Papers in Laryngology Since 2000.

OBJECTIVES/HYPOTHESIS: To identify the most influential publications in laryngology since 2000. STUDY DESIGN: Modified Delphi process. METHODS: Samples of laryngologists drawn from editors of leading journals, organization officers, and thought leaders were invited to participate in a modified Delphi identification of influential laryngology papers. Influential was defined as follows: yielding meaningful practice changes, catalyzing further work as a foundation for an important topic, altering traditional views, or demonstrating durability over time. Quality and validity were not among the selection criteria. Each participant nominated 5 to 10 papers in Round 1. These nominations, augmented with papers from bibliometric analysis, were narrowed further in Round 2 as participants identified their top 20. The 40 papers with the most Round 2 votes were discussed by video conference and then subjected to Round 3 voting, with each participant again selecting their top 20 most influential papers. Final results were collated by the number of Round 3 votes. RESULTS: Sixteen of 18 invited laryngologists participated overall (all 16 in Rounds 1 and 3; 14 in Round 2). Twenty-one papers were identified as most influential. One paper appeared on all 16 Round 3 lists; three papers with eight (50%) votes each were lasted to make the list. Eleven of these 21 focused on voice; three each related to cancer, airway, and swallowing; and one encompassed all of these clinical areas. CONCLUSIONS: This list of 21 influential laryngology papers serves to focus further research, provides perspective on recent advances within the field, and is an educational resource for trainees and practicing physicians. LEVEL OF EVIDENCE: NA Laryngoscope, 132:406-412, 2022.

Effect of Medialization on Dyspnea Index in Unilateral Vocal Fold Paralysis.

OBJECTIVE: Patients with unilateral vocal fold paralysis commonly report dysphonia and dysphagia. Dyspnea also occurs, with studies on treatment-related change producing mixed results. Studies including patient-reported outcomes have focused on single-question global scales. The Dyspnea Index (DI) includes 10 questions, is specific to upper airway-related dyspnea, and may better capture these patients' symptoms. We evaluated change in DI after treatment. STUDY DESIGN: Retrospective review. SETTING: Academic medical center. METHODS: Forty-three patients with unilateral vocal fold paralysis underwent injection augmentation (n = 25) or framework surgery (n = 18). DI was recorded preprocedure, 2 to 4 weeks afterward, and at approximately 3 months afterward in 19 patients. Voice Handicap Index-10, Glottal Function Index, Cough Severity Index, and Eating Assessment Tool-10 were also recorded. Change in parameters and correlations were assessed. Obesity, cardiac disease, pulmonary disease, and procedure (injection vs framework surgery) were evaluated for effect on DI. RESULTS: Twenty-four patients had an abnormal baseline DI (>10). DI decreased from 14.9 ± 13.8 to 6.5 ± 9.3 after treatment (P < .001; 95% CI, 4.7-12.1). Twenty-eight scores decreased, 9 remained unchanged, and 6 increased. Change in DI was influenced by the presence of cardiac disease. Decreased DI persisted at 3-month follow-up. Voice Handicap Index-10, Glottal Function Index, Cough Severity Index, and Eating Assessment Tool-10 scores decreased and were correlated with change in DI. CONCLUSION: Upper airway-related dyspnea is common in unilateral vocal fold paralysis, occurring in half of this cohort. Correcting glottic insufficiency may alleviate symptoms. Treatment decision making should consider postprocedural change in dyspnea, especially in patients for whom dyspnea is a motivating factor for seeking treatment.

Practice Patterns and Barriers in Botulinum Toxin Injection for the Treatment of Voice Disorders.

Laryngeal botulinum toxin injection is an important treatment modality for spasmodic dysphonia and other laryngeal disorders. We sought to compare usage patterns of laryngeal botulinum toxin injections for voice disorders and to identify and quantify inefficiencies and barriers in providing this treatment. A 26 item survey was written and approved for distribution by the American Academy of Otolaryngology-Head and Neck Surgery and the National Spasmodic Dysphonia Association. It was distributed to Otolaryngologists who perform laryngeal botulinum toxin injections via the e-mail lists of the National Spasmodic Dysphonia Association provider database, American Academy of Otolaryngology-Head and Neck Surgery Voice Committee and the American Laryngological Association Neurolaryngology Study Group. There were 81 survey participants who collectively reported performing >1700 laryngeal botulinum toxin injections for voice disorders monthly (Mean = 21.5 pts/month). Regarding botulinum toxin A (BtxA) vial use, 54% of participants reported using multiple doses per vial for different patients during a single clinic day, while 14% reported using pharmacy predrawn single use aliquots. A combination of usage practices was reported by 7% of participants. Using an individual vial per patient and discarding the unused remainder was reported by 26% of participants with an associated annual cost in wasted BtxA of $84,300 per physician. There is wide variation in injection practices regarding management of BtxA vials and adherence to an individual vial per patient policy is associated with significant waste of health care resources. Alternative approaches to BtxA vial use could positively impact health care resource utilization.

Wnt Signaling in Vascular Calcification.

Cardiovascular disease is a worldwide epidemic and considered the leading cause of death globally. Due to its high mortality rates, it is imperative to study the underlying causes and mechanisms of the disease. Vascular calcification, or the buildup of hydroxyapatite within the arterial wall, is one of the greatest contributors to cardiovascular disease. Medial vascular calcification is a predictor of cardiovascular events such as, but not limited to, hypertension, stiffness, and even heart failure. Vascular smooth muscle cells (VSMCs), which line the arterial wall and function to maintain blood pressure, are hypothesized to undergo a phenotypic switch into bone-forming cells during calcification, mimicking the manner by which mesenchymal stem cells differentiate into osteoblast cells throughout osteogenesis. RunX2, a transcription factor necessary for osteoblast differentiation and a target gene of the Wnt signaling pathway, has also shown to be upregulated when calcification is present, implicating that the Wnt cascade may be a key player in the transdifferentiation of VSMCs. It is important to note that the phenotypic switch of VSMCs from a healthy, contractile state to a proliferative, synthetic state is necessary in response to the vascular injury surrounding calcification. The lingering question, however, is if VSMCs acquire this synthetic phenotype through the Wnt pathway, how and why does this signaling occur? This review seeks to highlight the potential role of the canonical Wnt signaling pathway within vascular calcification based on several studies and further discuss the Wnt ligands that specifically aid in VSMC transdifferentiation.

First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland.

Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.

Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality.

BACKGROUND: Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. METHODS: Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. RESULTS: One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. CONCLUSIONS: The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. REGISTRATION: This review was registered on PROSPERO as CRD42020177714 .