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Introduction The purpose of this prospective study was to determine the effect of a combination of nitrous oxide/oxygen and 1 set of supplemental intraligamentary/periodontal ligament (PDL) injections followed by a second set of PDL injections on anesthetic success in patients with symptomatic irreversible pulpitis (SIP). Methods Ninety-four patients with a mandibular posterior tooth diagnosed with SIP received nitrous oxide/oxygen and an inferior alveolar nerve block (IANB) with 2% lidocaine with 1:100,000 epinephrine. Patients rated the pain of PDL injections and endodontic access on a visual analog scale. If moderate to severe pain was felt during treatment, the operator administered 1 set of supplemental PDL injections with 4% articaine with 1:100,000 epinephrine. If moderate to severe pain was felt again during treatment, the operator administered a second set of supplemental PDL injections. Anesthetic success was defined as having no to mild pain during endodontic treatment. Results The success of the IANB with nitrous oxide was 44% (95% confidence interval [CI], 34%–54%). The overall anesthetic success rate (IANB with PDL injections) was increased from 69% (95% CI, 60%–78%) with 1 set of PDL injections to 80% (95% CI, 72%–88%) with a second set of PDL injections. Conclusions Although the second set of PDL injections increased anesthetic success, it was not sufficient to ensure complete pulpal anesthesia.

1330 Objectives: 18F-fluciclovine and 68Ga-prostate-specific membrane antigen (PSMA) are PET radiotracers recommended for the localization of recurrent prostate cancer post-prostatectomy. We examined the positivity rates (planned secondary endpoint) of 18F-fluciclovine PET/CT and 68Ga-PSMA PET/CT in a randomized trial in patients with biochemical recurrence post-prostatectomy. Methods: The first 55 enrolled patients (accrual goal: 140) with detectable prostate-specific antigen (PSA) post-prostatectomy were randomized to undergo treatment planning based on either 18F-fluciclovine (mean dose: 9.85 ± 0.84 mCi) [Arm A] or 68Ga-PSMA (mean dose: 5.09 ± 0.15 mCi) with 20 mg Lasix given unless contraindicated [Arm B] in an ongoing prospective clinical trial. Two independent nuclear medicine physicians interpreted the PET scans by consensus. Final radiotherapy decisions were based on PET. Within the context of the trial, all lesions with abnormal radiotracer uptake, including equivocals, were treated as positive for recurrence unless proven as false positive. Positivity rates on 18F-fluciclovine and 68Ga-PSMA were compared on a whole body and region basis using chi-square or Fisher9s exact test. Results: Three patients dropped out before 18F-fluciclovine PET scanning; therefore, 52 patients were analyzed (26 patients in each arm). Median PSA was 0.28 ng/mL in the 18F-fluciclovine arm and 0.27 ng/mL in the 68Ga-PSMA arm. There was no significant difference in PSA (p = 0.96) and Gleason score at prostatectomy (p = 0.80) between groups. Nine patients had equivocal uptake in lesions: 3 prostate bed, 1 pelvic node, 1 paraaortic lymph node on 18F-fluciclovine, and 4 prostate bed on 68Ga-PSMA. No visceral lesion was detected with either modality. The overall positivity rate on 18F-fluciclovine was significantly higher than 68Ga-PSMA for whole body (96.2% vs 53.9%; p

The inferior alveolar nerve block (IANB) does not always result in successful pulpal anesthesia. Nitrous oxide may increase the success of the IANB. The purpose of this investigation was to study the effect of nitrous oxide/oxygen (N(2)O/O(2)) on IANB injection pain and mandibular pulpal anesthesia in asymptomatic subjects. One hundred five asymptomatic subjects received an IANB after the administration of N(2)O/O(2) or room air/oxygen (air/O(2)) at 2 separate appointments. After the IANB, subjects rated their level of pain for each phase of the injection (needle insertion, needle placement, and solution deposition) using a Heft Parker visual analog scale. Pulpal anesthesia was evaluated with an electric pulp tester for 60 minutes. The mean pain rating for all 3 injection phases showed a statistically significant reduction in pain when N(2)O/O(2) was used compared with Air/O(2) (P < .05). Odds ratios demonstrated a statistically significant increase in IANB success for the N(2)O/O(2) group compared with the air/O(2) group. N(2)O/O(2) administration statistically decreased pain for all 3 injection phases of the IANB. In addition, nitrous oxide statistically increased the likelihood of pulpal anesthesia for posterior mandibular teeth. However, the incidence of pulpal anesthesia was not 100%.

Background Lung transplant ischemia-reperfusion injury is typified by toxic metabolites and oxygen free radicals leading to worse graft function. Catalase is an enzyme involved in oxidative-stress detoxification. We hypothesize that direct delivery of highly concentrated polyethylene glycol-catalase (PEG-CAT) during normothermic ex vivo lung perfusion (EVLP) significantly reduces ischemia-reperfusion injury. Methods To demonstrate protection, primary culture porcine endothelial cells were treated with PEG-CAT (0 to 1250 U/mL) in a model of oxidative stress (400 μM H2 o 2). In vivo, rat lungs were subjected to 0 hours or 1 hour of warm ischemic injury and 2 hours of EVLP with or without PEG-CAT. Perfusate was collected throughout the perfusion duration and tissue was collected at the end. Tissue and perfusate underwent analysis for markers of apoptosis and a biometric signature of lung health. Results Uptake of PEG-CAT into primary endothelial cells was demonstrated with Alexa Fluor 488-labeled PEG-CAT. Oxidatively stressed cells pretreated with PEG-CAT had significantly decreased cytotoxicity and caspase 3/7 activity and increased cell viability and cell membrane integrity. In a rat model of warm ischemia with EVLP, PEG-CAT improved allograft viability as measured by indications of cell membrane integrity (lactate dehydrogenase and hyaluronic acid), presence of vasoconstrictive peptides (endothelin-1 and big endothelin-1) released from endothelial cells, and reduced apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling). Conclusions In vitro and ex vivo, PEG-CAT protects against oxidative stress-induced cytotoxicity, maintains cellular metabolism, and mitigates lung ischemia-reperfusion in an experimental model. Together, these data suggest that PEG-CAT is a potential therapeutic target for donor organs at risk for ischemia-reperfusion injury.

Training in research methods is a crucial component of the student experience in further and higher education. A common set of statistical and experimental design methods are taught across a broad ...

This article reviews the use of a subdiscipline of artificial intelligence (AI), deep learning , for the reconstruction of images in positron emission tomography (PET). Deep learning can be used either directly or as a component of conventional reconstruction, in order to reconstruct images from noisy PET data. The review starts with an overview of conventional PET image reconstruction and then covers the principles of general linear and convolution-based mappings from data to images, and proceeds to consider nonlinearities, as used in convolutional neural networks (CNNs). The direct deep-learning methodology is then reviewed in the context of PET reconstruction. Direct methods learn the imaging physics and statistics from scratch, not relying on a priori knowledge of these models of the data. In contrast, model-based or physics-informed deep-learning uses existing advances in PET image reconstruction, replacing conventional components with deep-learning data-driven alternatives, such as for the regularization. These methods use trusted models of the imaging physics and noise distribution, while relying on training data examples to learn deep mappings for regularization and resolution recovery. After reviewing the main examples of these approaches in the literature, the review finishes with a brief look ahead to future directions.

There is an urgent need for employees from diverse backgrounds in the health field. Community colleges are where many low-income and under-represented students begin their academic career. A career pipeline program was implemented at a community college to promote rigorous health careers, facilitate transfer success and develop information literacy skills. We assessed students’ confidence with fitting into a career, the impact of the program on students’ academic and career choices, salient program components, successes and challenges, and suggestions for improvement. Fifty-nine students enrolled in the program and 64% (n = 38) completed, all were minority students. Students reported increased confidence with fitting into their career and a positive impact on their choice of academic and career paths. Important aspects of the program were exposure to health professionals, mentoring, peer connections, academic and professional skill building, developing information literacy and experiential learning. Most students are either pursing a bachelor degree or have graduated with the intent of pursing graduate degree. Our experience demonstrates the feasibility of implementing a health career pipeline at a community college. Future programs should focus on career and academic skill building, information literacy, mentoring, peer connection, experiential activities, targeted outreach to male students, and facilitating the transfer process.

BackgroundAntibiotics are extensively prescribed in intensive care units (ICUs), yet little is known about how antibiotic-related decisions are made in this setting. We explored how beliefs, perceptions and contextual factors influenced ICU clinicians’ antibiotic prescribing.MethodsWe conducted 4 focus groups and 34 semistructured interviews with clinicians involved in antibiotic prescribing in four English ICUs. Focus groups explored factors influencing prescribing, whereas interviews examined decision-making processes using two clinical vignettes. Data were analysed using thematic analysis, applying the Necessity Concerns Framework.ResultsClinicians’ antibiotic decisions were influenced by their judgement of the necessity for prescribing/not prescribing, relative to their concerns about potential adverse consequences. Antibiotic necessity perceptions were strongly influenced by beliefs that antibiotics would protect patients from deterioration and themselves from the ethical and legal consequences of undertreatment. Clinicians also reported concerns about prescribing antibiotics. These generally centred on antimicrobial resistance; however, protecting the individual patient was prioritised over these societal concerns. Few participants identified antibiotic toxicity concerns as a key influencer. Clinical uncertainty often complicated balancing antibiotic necessity against concerns. Decisions to start or continue antibiotics often represented ‘erring on the side of caution’ as a protective response in uncertainty. This approach was reinforced by previous experiences of negative consequences (‘being burnt’) which motivated prescribing ‘just in case’ of an infection. Prescribing decisions were also context-dependent, exemplified by a lower perceived threshold to prescribe antibiotics out-of-hours, input from external team members and local prescribing norms.ConclusionEfforts to improve antibiotic stewardship should consider clinicians’ desire to protect with a prescription. Rapid molecular microbiology, with appropriate communication, may diminish clinicians’ fears of not prescribing or of using narrower-spectrum antibiotics.

Objective It is increasingly recognized that patient safety requires heterogeneous insights from a range of stakeholders, yet incident reporting systems in health care still primarily rely on staff perspectives. This paper examines the potential of combining insights from patient complaints and staff incident reports for a more comprehensive understanding of the causes and severity of harm. Methods Using five years of patient complaints and staff incident reporting data at a large multi-site hospital in London (in the United Kingdom), this study conducted retrospective patient-level data linkage to identify overlapping reports. Using a combination of quantitative coding and in-depth qualitative analysis, we then compared level of harm reported, identified descriptions of adjacent events missed by the other party and examined combined narratives of mutually identified events. Results Incidents where complaints and incident reports overlapped (n = 446, reported in 7.6%’ of all complaints and 0.6% of all incident reports) represented a small but critical area of investigation, with significantly higher rates of Serious Incidents and severe harm. Linked complaints described greater harm from safety incidents in 60% of cases, reported many surrounding safety events missed by staff (n = 582), and provided contesting stories of why problems occurred in 46% cases, and complementary accounts in 26% cases. Conclusions This study demonstrates the value of using patient complaints to supplement, test, and challenge staff reports, including to provide greater insight on the many potential factors that may give rise to unsafe care. Accordingly, we propose that a more holistic analysis of critical safety incidents can be achieved through combining heterogeneous data from different viewpoints, such as through the integration of patient complaints and staff incident reporting data.

Objective:The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.Design:The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.Methods:MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.Results:Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.Conclusions:MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.

Inflammatory odontogenic cysts are benign osteolytic asymptomatic lesions, but that, depending on the size, they can destroy the surrounding bone and let it infected. The term residual cyst is used most often for retained radicular cyst from teeth that has been removed. Residual cysts are among most common cysts of the jaws. This article aims to report characteristics and main aspects and highlighting the importance of the differential diagnosis for the treatment of these lesions. It can be concluded that early detection and accurate diagnosis are essential for the proper treatment of the residual cysts. Key Words- Residual cyst, radicular cyst, enucleation

Brief Background: Nisin’ is found naturally in dairy products and is also used as a preservative in food and beverages. It shows a rapid and broad spectrum activity against both gram-negative and gram-positive bacteria and hence could be used as a local drug delivery agent. Aim: To evaluate the clinical efficacy (Gingival Index GI, Probing Pocket Depth PPD, (Relative Attachment level RAL) of Scaling Root Planing (SRP) alone versus SRP with Nisin gel as LDD in pocket reduction therapy at baseline and after 3 months. Methodology: 30 sites in patients with chronic periodontitis with 5-7mm PPD were selected after taking informed consent. It was a split mouth study. Sites were divided into Group A Test group (15 sites) treated with SRP + LDD of Nisin gel and Group B control group (15 sites) treated with SRP alone. Clinical parameters were recorded at baseline and post treatment at 3 months. Results: It was observed that there was an improvement in clinical parameters in both the groups from baseline to 3 months post treatment, with Group A Test Group showing superior results. There was statistically significant improvement in Gingival Index in Group A as compared to Group B. PPD and RAL did not show statistically significant difference in both the groups. Summary and Conclusions: Nisin improves periodontal health and hence can be potentially used as an LLD agent. Keywords: Nisin, Preservative, Local drug delivery, Scaling root planing.

Organisational culture is assumed to be a key factor in large-scale and avoidable institutional failures (e.g. accidents, corruption). Whilst models such as “ethical culture” and “safety culture” have been used to explain such failures, minimal research has investigated their ability to do so, and a single and unified model of the role of culture in institutional failures is lacking. To address this, we systematically identified case study articles investigating the relationship between culture and institutional failures relating to ethics and risk management (n = 74). A content analysis of the cultural factors leading to failures found 23 common factors and a common sequential pattern. First, culture is described as causing practices that develop into institutional failure (e.g. poor prioritisation, ineffective management, inadequate training). Second, and usually sequentially related to causal culture, culture is also used to describe the problems of correction: how people, in most cases, had the opportunity to correct a problem and avert failure, but did not take appropriate action (e.g. listening and responding to employee concerns). It was established that most of the cultural factors identified in the case studies were consistent with survey-based models of safety culture and ethical culture. Failures of safety and ethics also largely involve the same causal and corrective factors of culture, although some aspects of culture more frequently precede certain outcome types (e.g. management not listening to warnings more commonly precedes a loss of human life). We propose that the distinction between causal and corrective culture can form the basis of a unified (combining both ethical and safety culture literatures) and generalisable model of organisational failure.

The importance of pain relief in farm animals has never been further up the agenda for modern food production and farm animal practice. This has been driven by increased awareness amongst farmers, veterinary surgeons and consumers. This article looks at the practical use of non-steroidal anti-inflammatory drugs (NSAIDs) in farm animal practice for both adults and youngstock. The basic mode of action of NSAIDs is discussed and some of the evidence base that has been growing over the use of NSAIDs in cattle. It also highlights some of the present requirements of some of the retailers and auditing bodies.

WHAT IS KNOWN ON THE SUBJECT?: Addiction has a devastating impact in the lives of millions of people worldwide. Siblings constitute a hidden population. Siblings' attitudes to addiction in the family vary widely from overinvolvement to disengagement among different individuals and across time-line points during the long history of addiction. Female siblings report more negative feelings and attitudes towards drugs and alcohol. Previous research has described the process of a sibling's substance abuse through the eyes of a co-sibling but did not focus on how co-siblings are affected personally. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Addiction can have a damaging traumatic impact on female siblings which is enhanced by social and self-stigmatizing processes related to the "code of silence." The anxiety provoking secret may devour the ability to communicate and connect with other members of their family and community if selective revelation proves to be unsuccessful. Ambiguous loss can occur when one's sibling abuses substances, as the sibling may be physically present yet be psychologically absent in terms of the co-sibling (and the family). Ambiguous loss is connected to the lack of understanding of the real impact of addiction on a sibling's personal development. Addiction constitutes a family trauma which may severely shake the siblings' beliefs and values and undermine their self-esteem, security and trust in life and the future. Lack of focus on a sibling's feelings during addiction may severely impact on his/her psychological health and identity development. IMPLICATIONS FOR PRACTICE: Understanding the experience of siblings may help health and social care professionals to develop compassion, patience and empathy towards family members of persons with addictions. Mental health nurses need to be aware of the devastating impact of addiction on all family members in order to validate their experiences and support them in recovering from trauma and loss in the family. Due to the current context of addiction services i.e. individualized approaches and limited resources, organizations should consider the need to provide effective clinical supervision to young mental health professionals at an individual, group or multidisciplinary level.

Background Identifying the optimal treatment in an acute postoperative setting remains a challenge. Multiple analgesic options are available, but comparing outcomes is limited by a lack of head-to-head trials. In addition, decisions based on efficacy only do not take drug safety into account. In such cases, multi-criteria decision analysis (MCDA) can be utilized to quantify and compare the efficacy and safety data of various drugs. Methodology The efficacy-safety profiles of eight parenteral, postoperative analgesics (acetaminophen, diclofenac, ketorolac, metamizole, morphine, nefopam, parecoxib, tramadol) widely used in Europe were evaluated using an MCDA model that included 17 criteria: three for efficacy and 14 for safety. Each drug was scored on each criterion on a scale from 0 (worst) to 100 (best), according to published data and the judgment of an expert panel. A weighting process was then applied to standardize the impact of each criterion and adjust drugs' preference scores accordingly, normalizing them on the 0-100 scale. Sensitivity analyses were also performed, including a model in which analgesic profiles were compared when opioid sparing effect was set at a zero value for all drugs. Results In the primary model, efficacy and safety had relative weightings of 64% and 36%, respectively. Efficacy and safety criteria with the highest values were pain relief (relative weight, 29%) and gastrointestinal effects (12%). Parecoxib received the highest overall score (93), followed by diclofenac (80), and ketorolac (75). Morphine scored the lowest (57), due to the lack of an opioid sparing effect. When opioid sparing was given a zero rating, parecoxib remained the highest scoring analgesic (93), followed by diclofenac (80), metamizole (76), and morphine (76). Parecoxib remained the most preferred analgesic in several other sensitivity analyses. Conclusion This MCDA-based assessment suggests that parecoxib has the most favorable efficacy-safety profile among the assessed postoperative analgesics.

We systematically reviewed the literature using unobtrusive measures to study organizational culture. To synthesize, theorize, and evaluate this research, we introduce the concept of an unobtrusive indicator of culture (UIC) for organizations. A UIC measures organizational culture through collecting data without engaging employees, and is conceptualized in terms of cultural artefacts. We identified thirty-five articles, containing 135 distinct UICs, drawn from 16 distinct data sources. UICs coalesced into two groups. First, textual UICs, with culture measured through language patterns in annual reports, employee online reviews, and emails. Second, UICs focusing on organizational practices, for instance, organizational policies or executive rewards. Over two-thirds (68%) of UICs measured values for integrity, results orientation, and clan cultures, and we conjecture that UICs may be most useful for studying aspects of culture sensitive to reporting biases, and benchmarking large samples of organizations. Forty-eight percent of UICs had good or promising construct validity: many were textual UICs, and those focusing on organizational practices were less established. UICs can potentially advance the study of organizational culture, yet must be developed and applied cautiously, with careful consideration of their advantages and limitations, and how they complement existing measurements and conceptualizations of culture.

Manifold alignment (MA) is a technique to map many high-dimensional datasets to one shared low-dimensional space. Here we develop a pipeline for using MA to reconstruct high-resolution medical images. We present two key contributions. Firstly, we develop a novel MA scheme in which each high-dimensional dataset can be differently weighted preventing noisier or less informative data from corrupting the aligned embedding. We find that this generalisation improves performance in our experiments in both supervised and unsupervised MA problems. Secondly, we use the wave kernel signature as a graph descriptor for the unsupervised MA case finding that it significantly outperforms the current state-of-the-art methods and provides higher quality reconstructed magnetic resonance volumes than existing methods.

Klebsiella pneumoniae is a gram-negative bacterium found in the environment and as a commensal in humans and animals. In humans, K. pneumoniae is one of the most serious nosocomial infections encountered currently and is characterized by liver abscesses, pneumonia, and bacteremia resulting in meningoencephalitis and endophthalmitis. K. pneumoniae in veterinary medicine is rarely reported in NHP, and recent literature describing this disease is sparse. In our colony of predominantly outdoor-housed rhesus macaques (Macaca mulatta), K. pneumoniae is cultured infrequently from healthy animals during routine screening and is even rarer in sick animals. This report summarizes the clinical and postmortem findings associated with this pathogen in 9 rhesus macaques and compares these results with the disease outcomes reported for humans. In these cases, K. pneumoniae infection was confirmed through culture or PCR testing or both. In our experience, when this bacterium does cause clinical signs, the disease is rapidly progressive and severe. At necropsy of NHP, the findings are strikingly similar to opportunistic Klebsiella-associated syndromes described in humans and include liver abscesses, meningoencephalitis, and endophthalmitis. In addition, many of the affected macaques had similar risk factors to humans that succumb to disease, thus perhaps indicating that rhesus macaques could be a viable model for investigating these syndromes.

Purpose A model-based reconstruction framework is proposed for motion-corrected and high-resolution anatomically assisted (MOCHA) reconstruction of arterial spin labeling (ASL) data. In this framework, all low-resolution ASL control-label pairs are used to reconstruct a single high-resolution cerebral blood flow (CBF) map, corrected for rigid-motion, point-spread-function blurring and partial volume effect. Methods Six volunteers were recruited for CBF imaging using pseudo-continuous ASL labeling, two-shot 3D gradient and spin-echo sequences and high-resolution T1 -weighted MRI. For 2 volunteers, high-resolution scans with double and triple resolution in the partition direction were additionally collected. Simulations were designed for evaluations against a high-resolution ground-truth CBF map, including a simulated hyperperfused lesion and hyperperfusion/hypoperfusion abnormalities. The MOCHA technique was compared with standard reconstruction and a 3D linear regression partial-volume effect correction method and was further evaluated for acquisitions with reduced control-label pairs and k-space undersampling. Results The MOCHA reconstructions of low-resolution ASL data showed enhanced image quality, particularly in the partition direction. In simulations, both MOCHA and 3D linear regression provided more accurate CBF maps than the standard reconstruction; however, MOCHA resulted in the lowest errors and well delineated the abnormalities. The MOCHA reconstruction of standard-resolution in vivo data showed good agreement with higher-resolution scans requiring 4-times and 9-times longer acquisitions. The MOCHA reconstruction was found to be robust for 4-times-accelerated ASL acquisitions, achieved by reduced control-label pairs or k-space undersampling. Conclusion The MOCHA reconstruction reduces partial-volume effect by direct reconstruction of CBF maps in the high-resolution space of the corresponding anatomical image, incorporating motion correction and point spread function modeling. Following further evaluation, MOCHA should promote the clinical application of ASL.

The literature on student agency is missing the voice and perspectives of teachers. Although theoretical and empirical research aims to explore student agency by observing and documenting t...

Older adults undergoing emergency abdominal surgery have significantly poorer outcomes than younger adults. For those who survive, the level of care required on discharge from hospital is unknown and such information could guide decision-making. The ELF (Emergency Laparotomy and Frailty) study aimed to determine whether preoperative frailty in older adults was associated with increased dependence at the time of discharge.The ELF study was a UK-wide multicentre prospective cohort study of older patients (65 years or more) undergoing emergency laparotomy during March and June 2017. The objective was to establish whether preoperative frailty was associated with increased care level at discharge compared with preoperative care level. The analysis used a multilevel logistic regression adjusted for preadmission frailty, patient age, sex and care level.A total of 934 patients were included from 49 hospitals. Mean(s.d.) age was 76·2(6·8) years, with 57·6 per cent women; 20·2 per cent were frail. Some 37·4 per cent of older adults had an increased care level at discharge. Increasing frailty was associated with increased discharge care level, with greater predictive power than age. The adjusted odds ratio for an increase in care level was 4·48 (95 per cent c.i. 2·03 to 9·91) for apparently vulnerable patients (Clinical Frailty Score (CFS) 4), 5·94 (2·54 to 13·90) for those mildly frail (CFS 5) and 7·88 (2·97 to 20·79) for those moderately or severely frail (CFS 6 or 7), compared with patients who were fit.Over 37 per cent of older adults undergoing emergency laparotomy required increased care at discharge. Frailty scoring was a significant predictor, and should be integrated into all acute surgical units to aid shared decision-making and discharge planning.Los adultos mayores sometidos a cirugía abdominal de urgencia tienen resultados significativamente peores que los adultos jóvenes. Para aquellos pacientes que sobreviven, el nivel de atención que requieren tras el alta hospitalaria se desconoce y esta información podría servir de guía en la toma de decisiones. El estudio ELF (Emergency Laparotomy and Frailty) tenía como objetivo determinar si la fragilidad preoperatoria en adultos mayores se asociaba con un aumento de la dependencia en el momento del alta. MÉTODOS: El estudio ELF era un estudio multicéntrico extenso efectuado en el Reino Unido (n = 49) que incluyó una cohorte prospectiva de 934 pacientes mayores ( 65 años) sometidos a laparotomía de urgencia durante marzo-junio de 2017. El objetivo fue establecer si la fragilidad preoperatoria aumentaba el nivel de asistencia en el momento del alta en comparación con el nivel de asistencia preoperatorio. Para el análisis se utilizó una regresión logística multinivel ajustada a características previas al ingreso: fragilidad, edad del paciente, género, y nivel de asistencia.La edad media de los pacientes fue 76,2 años (DE = 6,83), con un 57% de mujeres, un 20,2% de pacientes frágiles y un 37,4% de adultos mayores que presentaron un aumento en el nivel de asistencia en el momento del alta. Un aumento de la fragilidad se asoció con un incremento en el nivel de asistencia en el momento del alta (y mayor poder predictivo que la edad). La razón de oportunidades (odds ratio, OR) ajustada por el aumento del nivel de asistencia fue 4,48 (i.c. del 95% 2,03-9,91) para pacientes aparentemente vulnerables (Clinical Frailty Scale, CFS 4); 5,94 (i.c. del 95% 2,54-13,90) para aquellos ligeramente frágiles (CFS 5); y 7,88 (i.c. del 95% 2,97-20,79) para aquellos con fragilidad moderada o grave (CFS 6 and 7) en comparación con pacientes en buenas condiciones. CONCLUSIÓN: Este es el primer estudio que documenta que más del 37% de adultos mayores sometidos a laparotomía de urgencia precisaron un aumento en el nivel de asistencia en el momento del alta. La evaluación de la fragilidad debería integrarse en todas las unidades quirúrgicas de agudos para ayudar a compartir la toma de decisiones y los planes de tratamiento.

Families coping with Sickle Cell Disease (SCD) often face heightened psychosocial risk factors, and research in pediatric SCD has often focused more on this area than resiliency factors. The aim of this study was to gain a better understanding of family resiliency in SCD based on caregiver perspectives. A secondary qualitative analysis was conducted with data from a mixed-methods study of caregivers of youth with SCD (n = 22). Qualitative analyses involved coding based on two resiliency frameworks, organizing coding categories into themes, and systematically reintegrating these themes into a conceptualization that reflected family resiliency. Themes aligned well with the resiliency frameworks, and related to family belief systems and meaning-making around SCD (acceptance of SCD, positive attitude, religious faith), family organization and adaptation (flexibility, stability, social supports), and the importance of communication and problem-solving. Study findings emphasize the importance of assessing resilience in families of youth with SCD, and suggest the potential clinical benefits of developing psychosocial interventions based on family strengths.

Introduction\ud \ud Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction.\ud \ud \ud \ud Methods\ud \ud A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori.\ud \ud \ud \ud Results\ud \ud 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity.\ud \ud \ud \ud Conclusions\ud \ud Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups.

Purpose Numerous image reconstruction methodologies for positron emission tomography (PET) have been developed that incorporate magnetic resonance (MR) imaging structural information, producing reconstructed images with improved suppression of noise and reduced partial volume effects. However, the influence of MR structural information also increases the possibility of suppression or bias of structures present only in the PET data (PET-unique regions). To address this, further developments for MR-informed methods have been proposed, for example, through inclusion of the current reconstructed PET image, alongside the MR image, in the iterative reconstruction process. In this present work, a number of kernel and maximum a posteriori (MAP) methodologies are compared, with the aim of identifying methods that enable a favorable trade-off between the suppression of noise and the retention of unique features present in the PET data. Methods The reconstruction methods investigated were: the MR-informed conventional and spatially compact kernel methods, referred to as KEM and KEM largest value sparsification (LVS) respectively; the MR-informed Bowsher and Gaussian MR-guided MAP methods; and the PET-MR-informed hybrid kernel and anato-functional MAP methods. The trade-off between improving the reconstruction of the whole brain region and the PET-unique regions was investigated for all methods in comparison with postsmoothed maximum likelihood expectation maximization (MLEM), evaluated in terms of structural similarity index (SSIM), normalized root mean square error (NRMSE), bias, and standard deviation. Both simulated BrainWeb (10 noise realizations) and real [18 F] fluorodeoxyglucose (FDG) three-dimensional datasets were used. The real [18 F]FDG dataset was augmented with simulated tumors to allow comparison of the reconstruction methodologies for the case of known regions of PET-MR discrepancy and evaluated at full counts (100%) and at a reduced (10%) count level. Results For the high-count simulated and real data studies, the anato-functional MAP method performed better than the other methods under investigation (MR-informed, PET-MR-informed and postsmoothed MLEM), in terms of achieving the best trade-off for the reconstruction of the whole brain and PET-unique regions, assessed in terms of the SSIM, NRMSE, and bias vs standard deviation. The inclusion of PET information in the anato-functional MAP method enables the reconstruction of PET-unique regions to attain similarly low levels of bias as unsmoothed MLEM, while moderately improving the whole brain image quality for low levels of regularization. However, for low count simulated datasets the anato-functional MAP method performs poorly, due to the inclusion of noisy PET information in the regularization term. For the low counts simulated dataset, KEM LVS and to a lesser extent, HKEM performed better than the other methods under investigation in terms of achieving the best trade-off for the reconstruction of the whole brain and PET-unique regions, assessed in terms of the SSIM, NRMSE, and bias vs standard deviation. Conclusion For the reconstruction of noisy data, multiple MR-informed methods produce favorable whole brain vs PET-unique region trade-off in terms of the image quality metrics of SSIM and NRMSE, comfortably outperforming the whole image denoising of postsmoothed MLEM.

Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of action of CP include neutralizing antibodies but may extend beyond virus neutralization to include normalization of blood clotting and dampening of inflammation. Unresolved questions include the minimum therapeutic titer in the CP units or CP recipient as well as the optimal timing of administration. Here, we show that treatment of macaques with CP within 24 h of infection does not reduce viral shedding in nasal or lung secretions compared to controls and does not detectably improve any clinical endpoint. We also demonstrate that CP administration does not impact viral sequence diversity in vivo, although the selection of a viral sequence variant in both macaques receiving normal human plasma was suggestive of immune pressure. Our results suggest that CP, administered to medium titers, has limited efficacy, even when given very early after infection. Our findings also contribute information important for the continued development of the nonhuman primate model of COVID-19. These results should inform interpretation of clinical studies of CP in addition to providing insights useful for developing other passive immunotherapies and vaccine strategies. IMPORTANCE Antiviral treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain very limited. One treatment that was explored beginning early in the pandemic (and that is likely to be tested early in future pandemics) is plasma collected from people who have recovered from coronavirus disease 2019 (COVID-19), known as convalescent plasma (CP). We tested if CP reduces viral shedding or disease in a nonhuman primate model. Our results demonstrate that administration of CP 1 day after SARS-CoV-2 infection had no significant impact on viral loads, clinical disease, or sequence diversity, although treatment with normal human plasma resulted in selection of a specific viral variant. Our results demonstrate that passive immunization with CP, even during early infection, provided no significant benefit in a nonhuman primate model of SARS-CoV-2 infection.

Humans can survive a few minutes without access to air, a few days without water, and a few weeks without food. Even with access to these commodities, if they are contaminated then humans will suffer health problems. This chapter provides insights into the historical context for the eventual development of, and the recognized need for, clean water and clean air regulations, together with an appreciation of some of the technical challenges and political hesitancy that have been encountered in arriving at the modern regulations. Is this important? Yes; despite palpable improvements in water and air quality over the last three decades, estimates suggest that at least 7 million people die prematurely, annually, because of polluted air and contaminated water; at least four times more than the number of lives lost to COVID-19 in 2020, the first year of the global pandemic. Indeed, almost one-third of the global population does not have access to safe drinking water and over 90% live in areas that do not meet the air quality guidelines stipulated by the World Health Organization (WHO). These profound issues seldom receive the same level of attention as topics such as anthropogenic climate change forecasts, water scarcity, and carbon dioxide pollution, albeit students are taught that the global amount of water is inviolate, and that carbon dioxide is a non-contaminating, colorless, odorless, and incombustible gas. How then can there be a scarcity of water and how can a quite unreactive gas cause air pollution? Are humans solely responsible for unsafe water and harmful air? These are simple questions, but the answers are not; they are complex and often disputed.

Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 T cell influx into the cerebrospinal fluid. Our data show that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure., Graphical abstract, Verma et al. observe that prophylactic mAbs limit SARS-CoV-2 replication and immune activation. In aged diabetic rhesus macaques, these protective mechanisms took place in the areas of the body most highly targeted by the virus and the respiratory, nervous, and circulatory systems.

From our experience with rat lung transplantation, we have found several areas for improvement. Information in the existing literature regarding methods for choosing appropriate cuff sizes for the pulmonary vein (PV), pulmonary artery (PA), or bronchus (Br) are varied, thus making the determination of proper cuff size during rat lung transplantation an exercise of trial and error. By standardizing the cuffing technique to use the smallest effective cuff appropriate for the size of the vessel or bronchus, one can make the transplantation procedure safer, faster, and more successful. Since diameters of the PV, PA, and Br are related to the body weight of the rat, we present a strategy to choosing an appropriate size using a weight-based guide. Since lung volume is also related to body weight, we recommend that this relationship should also be considered when choosing the proper volume of air for donor lung inflation during warm ischemia as well as for the proper volume of PBS to be instilled during bronchoalveolar lavage (BAL) fluid collection. We also describe methods for 4(th) intercostal space dissection, wound closure, and sample collection from both the native and transplanted lobes.

Early in the SARS-CoV-2 pandemic, there was a high level of optimism based on observational studies and small controlled trials that treating hospitalized patients with convalescent plasma from COVID-19 survivors (CCP) would be an important immunotherapy. However, as more data from controlled trials became available, the results became disappointing, with at best moderate evidence of efficacy when CCP with high titers of neutralizing antibodies was used early in infection. To better understand the potential therapeutic efficacy of CCP, and to further validate SARS-CoV-2 infection of macaques as a reliable animal model for testing such strategies, we inoculated 12 adult rhesus macaques with SARS-CoV-2 by intratracheal and intranasal routes. One day later, 8 animals were infused with pooled human CCP with a high titer of neutralizing antibodies (RVPN NT50 value of 3,003), while 4 control animals received normal human plasma. Animals were monitored for 7 days. Animals treated with CCP had detectable levels of antiviral antibodies after infusion. In comparison to the control animals, they had similar levels of virus replication in the upper and lower respiratory tract, but had significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. By highlighting strengths and weaknesses, data of this study can help to further optimize nonhuman primate models to provide proof-of-concept of intervention strategies, and guide the future use of convalescent plasma against SARS-CoV-2 and potentially other newly emerging respiratory viruses., Author summary The results of treating SARS-CoV-2 infected hospitalized patients with COVID-19 convalescent plasma (CCP), collected from survivors of natural infection, have been disappointing. The available data from various studies indicate at best moderate clinical benefits only when CCP with high titer of neutralizing antibodies was infused early in infection. The macaque model of SARS-CoV-2 infection can be useful to gain further insights in the value of CCP therapy. In this study, animals were infected with SARS-CoV-2 and the next day, were infused with pooled human convalescent plasma, selected to have a very high titer of neutralizing antibodies. While administration of CCP did not result in a detectable reduction in virus replication in the respiratory tract, it significantly reduced lung inflammation. These data, combined with the results of monoclonal antibody studies, emphasize the need to use products with high titers of neutralizing antibodies, and guide the future development of CCP-based therapies.

Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder that is caused by expansion of a CAG-repeat tract in the huntingtin gene and characterized by motor impairment, cognitive decline, and neuropsychiatric disturbances. Neuropathological studies show that disease progression follows a characteristic pattern of brain atrophy, beginning in the basal ganglia structures. The HD Regulatory Science Consortium (HD-RSC) brings together diverse stakeholders in the HD community—biopharmaceutical industry, academia, nonprofit, and patient advocacy organizations—to define and address regulatory needs to accelerate HD therapeutic development. Here, the Biomarker Working Group of the HD-RSC summarizes the cross-sectional evidence indicating that regional brain volumes, as measured by volumetric magnetic resonance imaging, are reduced in HD and are correlated with disease characteristics. We also evaluate the relationship between imaging measures and clinical change, their longitudinal change characteristics, and within-individual longitudinal associations of imaging with disease progression. This analysis will be valuable in assessing pharmacodynamics in clinical trials and supporting clinical outcome assessments to evaluate treatment effects on neurodegeneration.

that is discontinuous to the primary tumor mass and forms secondary tumor masses in a distant area at the site of lodgment. Metastasis is a feature to distinguish malignant from benign tumors [1,2]. Worldwide, 19.3 million new cancer cases arise and about 10.0 millions of cancer deaths has occurred in 2020 [3]. In the year 2020 1,392,179 cases of cancer were reported in India, among which the breast, lung, mouth, cervix uteri, and tongue were the most commonly involved site. The head and neck, stomach, breast cancers are diagnosed in their locally advanced stage whereas, distant metastasis was predominant in lung cancer. Thus metastatic potential differs among the different type of cancer [4]. About 30% of patients with newly diagnosed solid tumors (other than melanomas) presents with clinically evident metastases. About 20% have hidden metastases at the time of diagnosis. It is stated that metastasis is the main cause for 90% of cancer deaths [1,2,5].

There is an urgent need for effective therapeutic interventions against SARS-CoV-2, including new variants that continue to arise. Neutralizing monoclonal antibodies have shown promise in clinical studies. We investigated the therapeutic efficacy of a combination of two potent monoclonal antibodies, C135-LS and C144-LS that carry half-life extension mutations, in the rhesus macaque model of COVID-19. Twelve young adult macaques (three groups of four animals) were inoculated intranasally and intra-tracheally with a high dose of SARS-CoV-2 and 24 hours later, treated intravenously with a high (40 mg/kg) or low (12 mg/kg) dose of the C135-LS and C144-LS antibody combination, or a control monoclonal antibody. Animals were monitored for 7 days. Compared to the control animals, animals treated with either dose of the anti-SARS-CoV-2 antibodies showed similarly improved clinical scores, lower levels of virus replication in upper and lower respiratory tract, and significantly reduced interstitial pneumonia, as measured by comprehensive lung histology. In conclusion, this study provides proof-of-concept in support of further clinical development of these monoclonal antibodies against COVID-19 during early infection., Author summary Monoclonal antibodies that neutralize SARS-CoV-2 have shown promise in treating recently infected individuals who are at high risk of progression to severe COVID-19 disease. Although several monoclonal antibodies are currently being used in the clinic, there is an ongoing need to develop additional antibodies. The ideal monoclonal antibodies, or combinations, should be potent and durable, and maintain activity against emerging viral variants. In this study, we tested a combination of two potent monoclonal antibodies, C135-LS and C-144-LS, engineered to have long half-lives, in the macaque model of SARS-CoV-2 infection. Animals treated early after infection fared better than placebo-treated controls, manifesting fewer clinical signs, less virus replication in the respiratory tract, and reduced lung inflammation. These promising data support clinical testing of these monoclonal antibodies in humans and further development of similar antibody-based prophylactic and therapeutic strategies.

Sialolithiasis is the formation of calcific concretions within the parenchyma or ductal system of the major or minor salivary glands, but it most commonly affects the submandibular salivarygland. Sialolithiasis usually occurs in adults aged 30 to 60 years and causes pathognomonicpain during meals. The treatment of sialolithiasis depends on the size and location of thecalculi. In this article we present a case report of giant sialolith in the submandibular salivary duct and review of literature of various diagnostic and treatment aspects. Key Words : Salivary stone, Calculi, submandibular sialolithiasis, sialoadenitis

Introduction The presence of healthy attached tissue at the tooth and implant soft tissue interface correlates with long-term success and stability in function and esthetics and requires conversion of unfavorable soft tissue traits to more favorable ones. Several soft tissue grafting procedures have been developed to improve both the volume of keratinized tissue and the soft tissue contour around implants and the tooth. Objectives This study therefore aims at determining the knowledge , attitude , and perception of Periodontists and implantologists in private practice towards soft tissue grafting around implants and teeth . Methodology Approximately 100 periodontists and dental practioners from Mumbai were provided with a questionnaire to evaluate their knowledge about soft tissue grafting around implants and teeth .The questionnaire consists questions regarding different techniques involved in soft tissue grafting , the materials used for it , the complications faced during the procedure and the preferred method . Results: The results show that very few practioners are practicing soft tissue grafting around natural teeth and implants in their private practice. Conclusion : Thus, keeping in mind the results of the study it is essential to create more awareness about soft tissue augmentation and its importance and also conduct programmes to train dentists for the same. Key Words : Teeth Replacement, awareness, attitude, patients, missing teeth, socioeconomic status.

Oral mucosa frequently encounters exophytic growth. Traumatic or irritation fibroma is a benign exophytic oral lesion that develops secondary to tissue.It is the benign reactive lesion, and the treatment of choice is surgical excision.In this case report we present a case of unusually large irritation or traumatic fibroma in left buccal mucosa. Key Words : Taumatic fibroma , Irritation fibroma , Benign tumour , Pedunculated growth

The pregnant patient who presents for dental treatment requires special attention. The purpose of this article is to provide concise information about the physiologic changes and oral pathologies associated with pregnancy and their potential complications. The treatment implications and the risk of various medications to the mother and foetus are also discussed. KEY WORDS : Pregnancy, physiologic changes, supine hypotension syndrome, drugs, guidelines.

Alveolar osteitis (AO) is the most common postoperative complication after tooth extraction. The pathophysiology, aetiology, prevention and treatment of the alveolar osteitis are very essential in oral surgery. The aim of this paperwas to provide a better basis for clinical management of the condition. In addition, the need for identification and elimination of the risk factors as well as preventive and symptomatic management of the condition are discussed. Key words : Alveolitis, alveolar osteitis, dry socket, extraction.

Piezoelectric surgery was first explained by French Jacques and Pierre Curie in 1880. Piezoelectric bone surgery is a novel osteotomy and osteoplasty technique invented by Professor Vercellotti in 1988 to overcome the limitations of traditional instrumentation in oral bone surgery by modifying and improving conventional ultrasound technology. The cutting action is the result of linear microvibrations, in amplitude between 30 and 200 μm that allow to obtain a micrometer precision in the range of 25-29 KHz modulated ultrasonic resonant frequency. Nerves, vessels, and soft tissue are preserved by the microvibrations (60 to 200 mm/sec), which are optimally adjusted to target only mineralized tissue. It is a minimally invasive osteotomy device to achieve unparallel precision, patient comfort, intra-operative sensitivity, intra-operative visibility, blood free surgical site and reduced damage to the surrounding soft tissues, osteocytes and important structures like nerves, muscles and mucosa. Also Piezosurgery is very useful in harvesting autogenous bone for regenerating periodontal defects. Various treatment modalities are based on removal of etiologic factors and preserving bone architecture. Recently this novel surgical approach has gained popularity in various fields of dental implantology, oral and maxillofacial surgery, endodontics, and orthopedics. This article aims to review the clinical calibre of piezosurgery in the field of periodontology and implant dentistry. Key Words : LESS INVASIVE, PRECISION CUTTING, MICRO VIBRATIONS, FASTER RECOVERY, PIEZO TECHNIQUE

Background Rapid molecular diagnostic tests to investigate the microbial aetiology of pneumonias may improve treatment and antimicrobial stewardship in intensive care units (ICUs). Clinicians’ endorsement and uptake of these tests is crucial to maximise engagement; however, adoption may be impeded if users harbour unaddressed concerns or if device usage is incompatible with local practice. Accordingly, we strove to identify ICU clinicians’ beliefs about molecular diagnostic tests for pneumonias before implementation at the point-of-care. Methods We conducted semi-structured interviews with 35 critical care doctors working in four ICUs in the United Kingdom. A clinical vignette depicting a fictitious patient with signs of pneumonia was used to explore clinicians’ beliefs about the importance of molecular diagnostics and their concerns. Data were analysed thematically. Results Clinicians’ beliefs about molecular tests could be grouped into two categories: perceived potential of molecular diagnostics to improve antibiotic prescribing (Molecular Diagnostic Necessity) and concerns about how the test results could be implemented into practice (Molecular Diagnostic Concerns). Molecular Diagnostic Necessity stemmed from beliefs that positive results would facilitate targeted antimicrobial therapy; that negative results would signal the absence of a pathogen, and consequently that having the molecular diagnostic results would bolster clinicians’ prescribing confidence. Molecular Diagnostic Concerns included unfamiliarity with the device’s capabilities, worry that it would detect non-pathogenic bacteria, uncertainty whether it would fail to detect pathogens, and discomfort with withholding antibiotics until receiving molecular test results. Conclusions Clinicians believed rapid molecular diagnostics for pneumonias were potentially important and were open to using them; however, they harboured concerns about the tests’ capabilities and integration into clinical practice. Implementation strategies should bolster users’ necessity beliefs while reducing their concerns; this can be accomplished by publicising the tests’ purpose and benefits, identifying and addressing clinicians’ misconceptions, establishing a trial period for first-hand familiarisation, and emphasising that, with a swift (e.g., 60–90 min) test, antibiotics can be started and refined after molecular diagnostic results become available.