Effect of early administration of dexamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome: EARLY-DEX COVID-19 trial.

Introduction and objectives: Corticosteroids are among the drugs demonstrating a mortality benefit for coronavirus disease 2019 (COVID-19). The RECOVERY trial highlighted that dexamethasone reduced 28-day mortality for hospitalized COVID-19 patients requiring either supplemental oxygen or mechanical ventilation. It is noted that approximately 30% of COVID-19 patients, initially presenting with mild symptoms, will advance to acute respiratory distress syndrome (ARDS), especially those with detectable laboratory markers of inflammation indicative of disease progression. Our research aimed to explore the efficacy of dexamethasone in preventing the progression to ARDS in patients hospitalized with COVID-19 pneumonia who do not yet require additional oxygen but are at high risk of developing ARDS, potentially leading to a reduction in morbimortality. Methods: In this multicenter, randomized, controlled trial, we evaluated the impact of dexamethasone on adult patients diagnosed with COVID-19 pneumonia who did not need supplementary oxygen at admission but were identified as having risk factors for ARDS. The risk of ARDS was determined based on specific criteria: elevated lactate dehydrogenase levels over 245 U/L, C-reactive protein levels exceeding 100 mg/L, and a lymphocyte count below 0.80 × 109/L. Participants were randomly allocated to either receive dexamethasone or the standard care. The primary endpoints included the incidence of moderate or severe ARDS and all-cause mortality within 30 days post-enrollment. Results: One hundred twenty-six patients were randomized. Among them, 41 were female (30.8%), with a mean age of 48.8 ± 14.4 years. Ten patients in the dexamethasone group (17.2%) and ten patients in the control group (14.7%) developed moderate ARDS with no significant differences. Mechanical ventilation was required in six patients (4.7%), with four in the treatment group and two in the control group. There were no deaths during hospitalization or during follow-up. An intermediate analysis for futility showed some differences between the control and treatment groups (Z = 0.0284). However, these findings were within the margins close to the region where the null hypothesis would not be rejected. Conclusion: In patients with COVID-19 pneumonia without oxygen needs but at risk of progressing to severe disease, early dexamethasone administration did not lead to a decrease in ARDS development. Clinical trial registration: ClinicalTrials.gov, identifier NCT04836780.

Association of Dose of Inhaled Corticosteroids and Frequency of Adverse Events.

BACKGROUND: Inhaled corticosteroids (ICS) are the cornerstone of asthma treatment and significantly improve morbidity and mortality. Adverse effects of oral corticosteroids are well documented, but less is known about ICS. METHODS: We conducted observational studies in adults with asthma using two different UK nationwide datasets: Clinical Practice Research Datalink (CPRD) Aurum and CPRD GOLD. The exposure was incident ICS; the outcomes were major adverse cardiac events (MACE), arrhythmia, pulmonary embolism (PE) and pneumonia over 12-months. Our main analyses used a cohort method with stabilized inverse probability treatment weighting to balance confounding between exposed and unexposed patients. Secondary analyses included nested case-control studies, and self-controlled case series. ICS was treated both as a categorical and continuous variable. Absolute risk was estimated using weighted flexible parametric models. FINDINGS: From 162,202 patients in our main cohort, there was an association with all outcomes at medium daily ICS dose or higher (HR, 95%CI at 201-599mcg: MACE=2.63, 1.66-4.15, arrhythmia=2.21, 1.60-3.04, PE=2.10, 1.37-3.22, pneumonia=2.25, 1.77-2.85; at ≥600mcg: MACE=4.63, 2.62-8.17, arrhythmia=2.91, 1.72-4.91, PE=3.32, 1.69-6.50, pneumonia=4.09, 2.98-5.60). There were no associations with lower doses of ICS. Secondary analyses produced similar results. The number needed to harm (95%CI) using 12-months of ICS 201-599mcg: MACE=473 (344-754), arrhythmia=567 (395-1006), PE=1221 (744-3388) and pneumonia=230 (177-327) and using ICS ≥600mcg: MACE=224 (148-461), arrhythmia=396 (228-1523), PE=577 (309-4311), pneumonia=93 (69-141). INTERPRETATION: Short-term use of low dose ICS was not associated with adverse effects. Moderate-high daily ICS doses were associated with an increased risk, but low-frequency, of cardiovascular events, pulmonary embolism and pneumonia. It is important for clinicians to adhere to guideline recommendations to use the lowest effective ICS dose.

Evaluation of immune and pyroptosis status in a model of sepsis-induced secondary pneumonia.

In recent years, researchers have focused on studying the mechanism of sepsis-induced immunosuppression, but there is still a lack of suitable animal models that accurately reflect the process of sepsis-induced immunosuppression. The aim of this study was to evaluate the immune status at various stages in a model of sepsis-induced secondary pneumonia and to demonstrate whether pyroptosis is one of the modes of immune cell death in sepsis. Firstly, we established a sepsis model in C57BL/6J mice using cecal ligation and puncture (CLP). The surviving mice were treated with a 40 µL suspension of P.aeruginosa (Pa) under anesthesia on day 4 post-CLP to establish a sepsis-induced secondary pneumonia model. Secondly, routine blood tests, serum ALT and PCT levels, gross lung specimens, and H&E staining of the lung and liver tissues were used to assess the successful establishment of this model. Serum levels of TNF-α and IL-6, the CD4+/CD8+ratio in blood, H&E staining of the spleen, and immunohistochemistry of CD4 and CD8 in the spleen were detected to evaluate the immune status of the model mice. Finally, the expression levels of pyroptosis-related proteins in the spleen were detected by Western blot. The expression of GSDMD was assessed using immunohistochemistry, and pyroptosis was directly observed through transmission electron microscopy. The experimental results above confirmed the successful construction of the model for sepsis-induced secondary pneumonia, demonstrating its ability to reflect sepsis-induced immunosuppression. Moreover, the expression of pyroptosis-related proteins, immunohistochemical GSDMD, and transmission electron microscopy of the spleen showed that pyroptosis was one of the modes of immune cell death in sepsis.

The correlation between the level of cellular classification in bronchoalveolar lavage fluid of children with severe Mycoplasma pneumoniae and clinical characteristics.

Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infection disease in children. To date, there have been few studies on the relationship between cytological changes in bronchoalveolar lavage fluid (BALF) and clinical features. The objective of this study is to investigate the correlation between changes in the proportion of cell classifications in BALF and the clinical features in children with severe MPP (SMPP). In total, the study included 64 children with SMPP requiring bronchoalveolar lavage who were admitted to our hospital between March and September 2022 (study group) and 11 children with bronchial foreign bodies without co-infection (control group), who were admitted during the same period. The proportion of cell classifications in BALF was determined by microscopic examination after performing Wright-Giemsa staining. Patients were grouped according to different clinical characteristics, and between-group comparisons were made regarding the variations in the proportion of cell classifications in BALF. The levels of blood routine neutrophil percentage (GRA%), C-reactive protein, D-dimer and lactate dehydrogenase in the study group were higher than those in the control group (P < 0.05). There were differences in the GRA% and macrophage percentage in the BALF between the two groups (P < 0.05). The GRA% and blood lymphocyte percentage were associated with pleural effusion. Multiple indicators correlated with extrapulmonary manifestations (P < 0.05). Moreover, the percentage of lymphocytes in the BALF correlated with pleural effusion, extrapulmonary manifestations and refractory MPP (RMPP) (P < 0.05). Logistic regression showed that BALF lymphocytes were protective factors for RMPP, while serum amyloid A and extrapulmonary manifestations were risk factors (P < 0.05). CONCLUSION: The BALF of children with SMPP is predominantly neutrophilic. A lower percentage of lymphocytes is related to a higher incidence of pleural effusion, extrapulmonary manifestations and progression to RMPP, as well as a longer length of hospitalisation. WHAT IS KNOWN: • Mycoplasma pneumonia in children is relatively common in clinical practice. Bronchoalveolar lavage (BAL) is a routine clinical procedure. WHAT IS NEW: However, there are relatively few studies focusing on the cytomorphological analysis of cells in BAL fluid.

Role of systemic immune-inflammatory index and systemic inflammatory response index in predicting the diagnosis of necrotizing pneumonia in children.

BACKGROUND: Necrotizing pneumonia (NP) is a rare serious complication of community-acquired pneumonia (CAP) in children, which is characterized by a protracted course of the disease and a prolonged hospital stay. This study aimed to assess the role of systemic immune-inflammatory index and systemic inflammatory response index in predicting early lung necrotization in children with CAP. METHODS: This study included all children hospitalized in Pediatric Pulmonology Unit, Tanta University, Egypt, with CAP between the ages of two months and 18 years. Systemic inflammatory indices, including the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), and systemic inflammation response index (SIRI), were calculated on patients' admission. RESULTS: The study involved a total of 228 children, 42 patients had NP, 46 patients had parapneumonic effusion, and 140 patients had non-complicated CAP. Patients with NP were substantially younger (p = 0.002), stayed in the hospital longer (p < 0.001), had a longer duration of symptoms before hospital admission (p < 0.001), and had fever for a longer duration than those in the other groups (p < 0.001). Regarding the inflammatory ratios, patients with NP had significantly higher MLR, PLR, SII, and SIRI than those in the other groups (p = 0.020, p = 0.007, p = 0.001, p = 0.037, respectively). ROC curve analysis showed that the combined SII + SIRI + D-dimer showed the highest AUC with a good specificity in predicting the diagnosis of NP. CONCLUSIONS: SII, SIRI, and D-dimer may be beneficial biomarkers for predicting the occurrence of NP in children when performed on patients' admission. In addition, it was found for the first time that combined SII + SIRI + D-dimer had a good sensitivity and specificity in the diagnosis of NP.

Accuracy of lung ultrasound performed with handheld ultrasound device in internal medicine: an observational study.

AIMS: Lung ultrasound (LUS) is increasingly used in Internal Medicine to complement medical examination, documenting pleural and lung conditions. This study aimed to compare the accuracy of handheld ultrasound device (HHUSD) with high-end ultrasound device (HEUSD) in patients with heart failure or pneumonia, also including the assessment of costs and time-savings. METHODS: In this observational study 72 patients (aged ≥ 18) admitted to Internal Medicine Unit for heart failure or pneumonia underwent LUS plus evaluation of inferior cava vein (ICV) when indicated, using both HHUSD and HEUSD. Each evaluation, independently performed by 2 different experienced operators, included B-lines number, pleural effusion, lung consolidations, ICV ectasia and its respiratory excursions. RESULTS: Concordance between HHUSD and HEUSD findings was 79.3% ± 17.7 (mean ± SD) for B-lines, 88.6% for pleural effusion, 82.3% for consolidations and 88.7% and 84.9% for ICV ectasia and its respiratory excursions respectively. BMI didn't significantly influence concordance between the two methods. Moreover, examination time (as mean ± SD) was shorter with HHUSD (8 ± 1.5 min) compared to HEUSD (10 ± 2.5 min). CONCLUSIONS: HHUSD demonstrated high accuracy in detecting B-lines, pleural effusions, lung consolidations and ICV evaluation when compared to HEUSD. Thus, HHUSD, not only is characterized by accessibility, portability, and easy handling due to its small size, but it also offers advantages in terms of saving costs and time, ultimately contributing to faster patient assessment compared to HEUSD.

Granular cell tumour-A case of recurrent pneumonia due to an endobronchial lesion.

Granular cell tumours are rare, mostly benign masses that arise from Schwann cells. Their pathophysiology is poorly understood, but the lesions are often seen in the breast, tongue, and skin. In this case report, we discuss a 34-year-old patient with recurrent pneumonia. The patient had several comorbidities, and was intubated due to respiratory distress and eventually placed on tracheostomy. During the procedure, she was noted to have a right middle lobe endobronchial lesion. It was excised and identified as a granular cell tumour. The patient was later weaned off the ventilator and discharged without any complications.

Pathogen kinetics and detection by next-generation sequencing in pediatric complicated pneumonia.

Pediatric pneumonia can be severe and result in empyema. Next-generation sequencing (NGS) may broadly detect pathogens though, optimal timing and impact of sample type on diagnostic yield is unknown. This is a prospective, single-center pilot study of children aged 3 months through 17 years admitted to the PICU with a primary diagnosis of complicated pneumonia. Plasma, endotracheal, nasopharyngeal, and pleural fluid samples were collected at three time points during hospitalization. After nucleic acid extraction, combined libraries were enriched with an NGS enrichment panel kit (RPIP, Illumina), sequenced and quantitative organism detections were analyzed. NGS identified the same bacterial pathogen as traditional testing in all samples, regardless of antibiotic pre-treatment or time collected. Conventional culture methods only identified the pathogen reliably in invasively obtained pleural fluid or endotracheal aspirates. Future application of NGS may allow for non-invasive pathogen detection at a broader range of time points and more targeted antibiotic coverage.

Outcome of Intravenous and Inhaled Polymyxin B treatment in Patients with Multidrug-Resistant Gram-Negative Bacterial Pneumonia.

PURPOSE: The incidence of pneumonia caused by multidrug-resistant gram-negative bacteria (MDR GNB) is increasing, which imposes significant burden on public health. Inhalation combined with intravenous polymyxins has emerged as a viable treatment option. However, pharmacokinetic studies focusing on intravenous and inhaled polymyxin B (PMB) are limited. METHODS: This study included seven patients with MDR GNB-induced pneumonia who were treated with intravenous plus inhaled PMB from March 1 to November 30, 2022, in the intensive care unit of the First Affiliated Hospital of Zhejiang University School of Medicine. Clinical outcomes and therapeutic drug monitoring data of PMB in both plasma and epithelial lining fluid (ELF) were retrospectively reviewed. RESULTS: Median PMB concentrations in the ELF were 7.83 (0.72-66.5), 116.72 (17.37-571.26), 41.1 (3.69-133.78), and 33.82 (0.83-126.68) mg/L at 0, 2, 6, and 12 h, respectively, and were much higher than those detected in the serum. ELF concentrations of PMB at 0, 2, 6, and 12 h were higher than the minimum inhibitory concentrations of pathogens isolated from the patients. Steady-state concentrations of PMB in the plasma were > 2 mg/L in most patients. Of the patients, 57.14 % were cured and 71.43 % showed a favorable microbiological response. The incidence of side effects with PMB was low. CONCLUSIONS: Inhaled plus intravenous PMB can achieve high ELF concentrations and favorable clinical outcomes without an increased adverse effect profile. This treatment approach appears promising for the treatment of patients with pneumonia caused by MDR-GNB.

Assessing the diagnostic utility of serum tumor markers for lung cancer detection in patients with interstitial pneumonia.

BACKGROUND: The prevalence of lung cancer among individuals afflicted with interstitial pneumonia (IP) stands at approximately 20%. The early detection of lung cancer via chest computed tomography (CT) surveillance proves challenging in IP patients. Our investigation sought to identify a potential biomarker capable of providing early indications of the presence of lung tumors in such patients. MATERIALS AND METHODS: We examined the attributes of serum tumor markers, imaging characteristics, and histological findings in individuals diagnosed with IP, both with and without concurrent lung cancer. RESULTS: 106 patients diagnosed with IP were included in the study, comprising 36 individuals with concurrent lung cancer and 70 patients solely diagnosed with IP. Serum concentrations of CEA and CA12-5 were notably elevated in IP patients with lung cancer, compared to those with IP alone. Logistic regression analyses revealed that, in comparison to IP patients within the first quartile of CEA levels, the relative risk of developing lung cancer associated with IP escalated by 4.0-fold, 3.1-fold, 11.0-fold, and 13.3-fold in the second, third, fourth, and fifth quartiles, respectively. Upon controlling for gender and age, statistical significance in risk was observed solely for the fourth and fifth quartiles. Receiver operating characteristic (ROC) curve analysis conducted in patients diagnosed with ILD-CA identified a CEA cutoff point of 6.9 ng/mL, demonstrating sensitivities of 61.1% and specificities of 78.5%. The area under the curve was calculated as 0.7(95% CI: 0.63-0.81). CONCLUSION: The serum levels of CEA were notably elevated in IP patients with concurrent lung cancer in contrast to those who were just suffering from IP. The heightened serum CEA levels correlate with an escalated risk of cancer occurrence among IP patients, suggesting that serum CEA levels could potentially serve as an indicative marker for the presence of cancer in IP patients.

Mortality Rate of COVID-19 With Comorbid Pneumonia in a Rural Area.

BACKGROUND: A myriad of risk factors and comorbidities have been determined to influence COVID-19 mortality rates; among these is pneumonia. This study considers pneumonia as a risk factor for increased mortality in patients admitted with COVID-19 in a rural healthcare system. We predicted that the presence of pneumonia of any kind would increase mortality rates in patients admitted with COVID-19. METHODS: A retrospective observational study was conducted using data collected from hospitals in the Freeman Health System (FHS) located in Joplin and Neosho, Missouri. Data were collected between April 1, 2020, and December 31, 2021. Using International Classification of Diseases, Tenth Revision (ICD-10) codes, the investigators identified five distinct patient populations: patients with COVID-19 and pneumonia due to COVID-19 (P1); patients with COVID-19 but without pneumonia due to COVID-19 (P2); patients with COVID-19 and any type of pneumonia (P3); patients with COVID-19 but without any type of pneumonia (P4); and patients without COVID-19 and with any type of pneumonia (P5). In order to understand how pneumonia influences COVID-19 outcomes, the investigators used Wald's method and a two-sample proportion summary hypothesis test to determine the confidence interval and to compare the mortality rates between these populations, respectively. RESULTS: The population of patients with COVID-19 and any type of pneumonia (P3) and the population of patients with COVID-19 and pneumonia due to COVID-19 (P1) showed the highest mortality rates. The population of patients with COVID-19 but without any type of pneumonia (P4) had the lowest mortality rate. The data revealed that having pneumonia combined with COVID-19 in any patient population led to a higher mortality rate than COVID-19 alone. CONCLUSION: Mortality rates were higher among COVID-19 patients with pneumonia compared to COVID-19 patients without pneumonia. Additionally, pneumonia, by itself, was found to have a higher mortality rate compared to COVID-19 alone.

A Rare Occurrence of Methicillin-Resistant Staphylococcus aureus (MRSA) Pneumonia Complicated by Nasal Vestibulitis and Orbital Cellulitis: A Case Report.

We report the case of left lower lobe community-acquired methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in an immunocompetent male in his 20s. His illness was complicated by the dramatic appearance of right nasal vestibulitis and right preseptal orbital cellulitis post-admission. The patient responded well to vancomycin and made a complete recovery. Community-acquired MRSA pneumonia in immunocompetent adults is a rare entity in India, and the combination with vestibulitis has not yet been reported. This hitherto unreported presentation sheds further light on the evolving pattern of MRSA infections in the community.

A Retrospective Comparison of Clinical and Laboratory Aspects of Patients With COVID-19-Related Acute Respiratory Distress Syndrome (ARDS) and Non-COVID-19-Related ARDS.

AIM/OBJECTIVE: This study investigated demographic characteristics, hemodynamic values, respiratory datas, laboratory values ​​such as biochemistry and blood gas, and treatment approaches of coronavirus disease 2019 (COVID-19)-related and non-COVID-19-related acute respiratory distress syndrome (ARDS) patients hospitalized in the intensive care unit (ICU). BACKGROUND: Determining the differences and similarities between COVID-19-related ARDS (CARDS) patients and non-COVID-19-related ARDS (NCARDS) patients will be useful to better understand these two diseases. MATERIALS AND METHODS: A total of 32 NCARDS patients who were followed and treated in the ICU for various reasons between January 2015 and December 2020 and 32 CARDS patients who were followed and treated in the ICU for various reasons between March 2020 and December 2020 were examined retrospectively. Age, gender, comorbidities, Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE) II Score, blood pressure, heart rate, saturation, laboratory results, arterial blood gas (ABG) values, length of stay in the ICU, intubation, the number of days till the patient was extubated, the treatments applied, admission to the service, and mortality were evaluated. RESULTS: In the comparison between the two groups, the demographic data of the patients, the number of days intubated and extubated, APACHE II scores, and ICU length of stay were not statistically different. Values of positive end-expiratory pressure (PEEP), first hospitalization GCS, first hospitalization hemoglobin (Hgb), albumin at first admission, alanine aminotransferase (ALT) at first admission, and steroid use were found to be significantly different in patients with CARDS (p < 0.001). The median of PEEP values (p = 0.04), first admission GCS values (p = 0.04), first admission Hgb values (p = 0.005), albumin values at the first admission (p = 0.03), ALT values (p = 0.03), and the rate of steroid use (p = 0.001) of CARDS patients were significantly higher than those of NCARDS patients. The median of the first hospitalization heart rate values (p = 0.009), first hospitalization saturation values (p = 0.001), and first admission neutrophil values (p = 0.03) in NCARDS patients were significantly higher than that of CARDS patients. There was no significant difference between the two groups in terms of mortality, sedation use, inotropic support, C-reactive protein (CRP), and procalcitonin values. CONCLUSIONS: CARDS and NCARDS have clinical and laboratory similarities and differences. Therefore, there should be differences in our follow-up and treatment approach to these two disease groups.

Clinical differences between Mycoplasma pneumoniae pneumonia and Streptococcus pneumoniae pneumonia: a case control study.

Introduction: Mycoplasma pneumoniae pneumonia (MPP) and Streptococcus pneumoniae pneumonia (SPP) are frequent causes of respiratory tract infection, the aims of the study were to explore the differences in clinical features between children with MPP and those with SPP. Methods: This retrospective study included admitted children who were diagnosed with MPP or SPP over 5 years from January 2015 to January 2020. Children with MPP were compared to children with SPP in terms of clinical features. Results: 506 patients with MPP were compared to 311 patients with SPP in terms of clinical differences. The MPP group with a median age of 60 [29-89] months and the SPP group with a median age of 24 [10-40] months. Patients with MPP were older and had a higher occurrence of receiving antibiotics before admission, fever, dry cough, polypnea and diarrhea than patients with SPP (all p < 0.01). Patients with SPP were more likely to have wheezing, cyanosis and irritability (all p < 0.01). Laboratory findings in our study showed that there were significant differences between MPP and SPP patients in mean leucocyte count, neutrophil % (N%), lymphocyte % (L%), ALT levels, AST levels, LDH levels and incidence of accelerated procalcitonin (PCT) (all p < 0.01). Lower age, no dry cough, no polypnea, lower LDH levels, and higher PCT might lead to the diagnosis of SPP. Our study showed that age had a higher accuracy in predicting MPP than LDH levels, with an age >48.5 months shown to be an independent predictive factor for the early evaluation and identification of MPP. Discussion: In conclusion, patients with MPP and SPP usually present with fever, cough and some nonspecific symptoms. Our study showed that age, dry cough, polypnea, LDH levels, and PCT levels were independent predictive factors associated with MPP and SPP.

Progressive Lung Consolidation in HIV Amidst the COVID-19 Pandemic: Evaluating Probable Cytomegalovirus Pneumonia and the Importance of Early Empirical Treatment.

We present the case of a young male who was diagnosed with HIV in 2012. However, his initiation of antiretroviral therapy (ART) was delayed until 2018 due to issues related to his acceptance and acknowledgment of the disease. In April 2021, the patient presented with hemoptysis, shortness of breath, and constitutional symptoms. Initial extensive workup for tuberculosis (TB) and other respiratory pathogens returned negative. Despite this, he was treated for smear-negative pulmonary TB and pneumocystis pneumonia (PCP) and was subsequently discharged. He then had recurrent hospital admissions due to worsening respiratory symptoms, with short intervals between recovery and recurrence. Each admission saw an increase in his oxygen requirements. Throughout these hospitalizations, tests for coronavirus disease 2019 (COVID-19) were consistently negative. TB and PCP treatment continued throughout his admissions. Despite various treatments, his condition continued to deteriorate. A DNA polymerase chain reaction (DNA PCR) test for cytomegalovirus (CMV) was eventually conducted. Unfortunately, the patient succumbed to progressive respiratory failure, and the CMV DNA PCR returned positive a week after his death. In the era of COVID-19, this case underscores the importance of early diagnosis and timely antiviral treatment.

Changing the Conversation: Empowering Community Pharmacists to Address Pneumococcal Vaccine Hesitancy.

BACKGROUND: Although pneumococcal vaccine is recommended for everyone 65 years of age and older, only 58% of Canadians in this age group have been vaccinated, well below the Public Health Agency of Canada's target of 80%. To improve uptake, a stepped-wedge cluster randomized trial testing the effectiveness of a community pharmacist intervention was developed. OBJECTIVE: This pre-specified sub-study aimed to uncover and quantify factors contributing to vaccine hesitancy by exploring the nature of patient-pharmacist conversations about pneumococcal vaccine. METHODS: Beginning each month (April to August 2023), participating pharmacies were randomly selected to receive an education package designed to enhance pharmacists' knowledge, skills, and abilities in promoting pneumococcal vaccination. Pharmacists provided usual care (control stage) until they received the educational package and transitioned to the intervention stage. Weekly scorecards tracked patient-pharmacist conversations about pneumococcal vaccination. Chi-squared tests compared time taken for each conversation and patient-reported reason(s) for refusal between control and intervention stages. RESULTS: Thirteen pharmacies from across Alberta were included in the analysis, reporting 656 patient-pharmacist conversations (control stage n=271, intervention stage n=385). Time taken for pneumococcal vaccine conversations decreased after pharmacies received the education package (65% of conversations resulting in vaccination took <20 minutes in the control stage, compared to 88% in the intervention stage (p=0.004)). The most common patient-reported reason for refusal, needing more time to think about the vaccine, remained similar between stages (p=0.23). However, during the intervention stage, fewer patients refused vaccination due to lack of time to receive it today (p=0.016) and perceived lack of benefit (p=0.035), but more patients refused vaccination due to cost barriers (p=0.026). CONCLUSION: The education provided in this study changed the reasons for refusing vaccines, suggesting the nature of patient-pharmacist conversations became more efficient and informed. Similar interventions could be adopted across Canada and the US to help combat vaccine hesitancy.

Effects of titration speed, gender, obesity and concomitant medications on the risk and onset time of clozapine-associated fever among Japanese patients with schizophrenia: retrospective review of charts from 21 hospitals.

BACKGROUND: Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation. AIMS: We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date. METHOD: We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days. RESULTS: Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset. CONCLUSION: A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications.

Perception of pneumocystis jirovecii pneumonia (PJP) prophylaxis in glioma patients receiving concurrent temozolomide and radiation- a patient and physician survey.

PURPOSE: Pneumocystis jirovecii pneumonia (PJP) prophylaxis is required by provincial and national drug monographs during glioma treatment using temozolomide (TMZ) concurrently with radiation (TMZ-RT). However, real-world data suggest the potential benefits of PJP prophylaxis may not outweigh its potential harms in this population. METHODS: We conducted a single-center patient survey and a national physician survey to explore the role of PJP prophylaxis amongst glioma patients undergoing TMZ-RT. RESULTS: 23% (31/133) of physicians and 60% (44/73) of patients completed a survey. The median patient age was 42 (range 20-77); 85% (34/40) had completed adjuvant TMZ. Although only 2.4% (1/41) of patients received PJP prophylaxis, only one person (without PJP prophylaxis) was hospitalized for pneumonia. When presented with hypothetical PJP risks, 13.2% (5/38) of patients were concerned about PJP infection, while 26% (10/38) were concerned about potential side effects from prophylactic antibiotics. Most physicians (77%, 17/22) perceived the evidence for PJP prophylaxis as weak; 58% (11/19) did not routinely prescribe prophylaxis, and 73% (16/22) felt that PJP prophylaxis should be limited to patients with additional risk factors. Over 95% of physicians estimated that the incidence of PJP was < 1% in their last 5 years of practice regardless of PJP prophylaxis. For 73% (16/22) of physicians, to prescribe PJP prophylaxis, the risk of PJP infection needed to be 3-8%. CONCLUSION: The current recommendation to routinely prescribe PJP prophylaxis in patients receiving TMZ-RT in the absence of other risk factors warrants reconsideration.

Predictive signature of murine and human host response to typical and atypical pneumonia.

BACKGROUND: Pneumonia due to typical bacterial, atypical bacterial and viral pathogens can be difficult to clinically differentiate. Host response-based diagnostics are emerging as a complementary diagnostic strategy to pathogen detection. METHODS: We used murine models of typical bacterial, atypical bacterial and viral pneumonia to develop diagnostic signatures and understand the host's response to these types of infections. Mice were intranasally inoculated with Streptococcus pneumoniae, Mycoplasma pneumoniae, influenza or saline as a control. Peripheral blood gene expression analysis was performed at multiple time points. Differentially expressed genes were used to perform gene set enrichment analysis and generate diagnostic signatures. These murine-derived signatures were externally validated in silico using human gene expression data. The response to S. pneumoniae was the most rapid and robust. RESULTS: Mice infected with M. pneumoniae had a delayed response more similar to influenza-infected animals. Diagnostic signatures for the three types of infection had 0.94-1.00 area under the receiver operator curve (auROC). Validation in five human gene expression datasets revealed auROC of 0.82-0.96. DISCUSSION: This study identified discrete host responses to typical bacterial, atypical bacterial and viral aetiologies of pneumonia in mice. These signatures validated well in humans, highlighting the conserved nature of the host response to these pathogen classes.