Epidemiology, Risk Factors, and Prophylaxis Use for Pneumocystis jirovecii Pneumonia in the Non-HIV Population: A Retrospective Study in Québec, Canada.

Background: Pneumocystis jirovecii pneumonia (PJP) remains a significant threat in immunocompromised cases. Recent data on epidemiology and risk factors for PJP in non-HIV cases are scarce, and guidelines on appropriate prophylaxis are lacking. Methods: In this multicenter retrospective trial, all non-HIV adult cases admitted to hospitals in Québec City, Canada, between January 2011 and January 2021 with a diagnosis of PJP were assessed for eligibility. Results: An overall 129 cases of PJP were included. More than two-thirds had an underlying hematologic disease or an autoimmune/inflammatory condition. Prior to diagnosis, 83.7% were taking corticosteroids, 71.3% immunosuppressive agents (alone or in combination with corticosteroids), and 62% both. A diagnosis of PJP was noted in 22 patients receiving corticosteroids for treatment <28 days. Two patients developed PJP while undergoing corticosteroid monotherapy at a mean daily prednisone-equivalent dose <20 mg/d; 4.7% of our cohort received a PJP prophylaxis. Current recommendations or accepted clinical practices for PJP prophylaxis would not have applied to 48.8% of our patients. Conclusions: The use of corticosteroids-in monotherapy or in coadministration with other immunosuppressive agents-remains the principal risk factor for PJP in the non-HIV population. Current prophylaxis guidelines and accepted practices are insufficient to adequately prevent PJP and need to be broadened and updated.

Modelling the potential increase in eligible participants in clinical trials with inclusion of community intensive care unit patients in Alberta, Canada: a decision tree analysis.

PURPOSE: Critical care research in Canada is conducted primarily in academically affiliated intensive care units (ICUs) with established research infrastructure. Efforts are made to engage community hospital ICUs in research, although the impacts of their inclusion in clinical research have never been explicitly quantified. We therefore sought to determine the number of additional eligible patients that could be recruited into critical care trials and the change in time to study completion if community ICUs were included in clinical research. METHODS: We conducted a decision tree analysis using 2018 Alberta Health Services data. Patient demographics and clinical characteristics for all ICU patients were compared against eligibility criteria from ten landmark, randomized, multicentre critical care trials. Individual patients from academic and community ICUs were assessed for eligibility in each of the ten studies, and decision tree analysis models were built based on prior inclusion and exclusion criteria from those trials. RESULTS: The number of potentially eligible patients for the ten trials ranged from 2,082 to 10,157. Potentially eligible participants from community ICUs accounted for 40.0% of total potentially eligible participants. The recruitment of community ICU patients in trials would have increased potential enrolment by an average of 64.0%. The inclusion of community ICU patients was predicted to decrease time to trial completion by a mean of 14 months (43% reduction). CONCLUSION: Inclusion of community ICU patients in critical care research trials has the potential to substantially increase enrolment and decrease time to trial completion.

RéSUMé: OBJECTIF: La recherche en soins intensifs au Canada est principalement réalisée dans des unités de soins intensifs affiliées à des centres universitaires jouissant d'infrastructures de recherche bien établies. Des efforts ont été déployés pour engager les unités de soins intensifs des hôpitaux communautaires en recherche, mais les impacts de leur participation à la recherche clinique n'ont jamais été explicitement quantifiés. Nous avons conséquemment cherché à déterminer le nombre de patient·es additionnel·les pouvant être recruté·es dans des études de soins critiques ainsi que la variation du temps nécessaire pour compléter les études si la patientèle issue d'unités de soins intensifs d'hôpitaux communautaires participait à la recherche clinique. MéTHODE: Une analyse par arbre de décision a été réalisée à partir de données provenant des Alberta Health Services pour l'année 2018. Les données démographiques et les caractéristiques cliniques de tou·tes les patient·es admis·es aux soins intensifs ont été comparées avec les critères d'éligibilité de dix importantes études multicentriques, randomisées, contrôlées en soins intensifs. Les patient·es des unités de soins intensifs universitaires et communautaires ont tou·tes été évalué·es pour leur éligibilité à chacune des dix études, et des modèles d'arbres décisionnels ont été construits en se basant sur les critères originaux d'inclusion et d'exclusion. RéSULTATS: Le nombre de personnes potentiellement éligibles pour les dix études s'est situé entre 2082 et 10 157. Les patient·es potentiellement admissibles en provenance d'unités de soins intensifs communautaires ont représenté 40,0 % de toutes les personnes potentiellement admissibles. Le recrutement de patient·es en provenance d'unités de soins intensifs communautaires aurait permis une hausse moyenne du recrutement potentiel de 64,0 %. L'inclusion de patient·es des unités de soins intensifs communautaires pourrait également réduire le temps nécessaire à la complétion des études de 14 mois en moyenne (réduction de 43 %). CONCLUSION: L'inclusion de patient·es en provenance d'unités de soins intensifs d'hôpitaux communautaires dans la recherche clinique en soins critiques a le potentiel d'augmenter substantiellement le recrutement et de diminuer le temps nécessaire à la complétion des études.

A 37-Year-Old Man With Right Lung Consolidation.

CASE PRESENTATION: A 37-year-old man attended a medical clinic at the confluence of the Appalachian and the St. Lawrence Valley after 2 weeks of coughing greenish sputum and progressive dyspnea on exertion. In addition, he reported fatigue, fevers, and chills. He had quit smoking a year earlier and was not a drug user. He recently had spent most of his free time outdoors, mountain biking, but had not travelled outside of Canada. Medical history was unremarkable. He did not take any medication. Upper airway samples taken for SARS-CoV-2 proved negative; he was prescribed cefprozil and doxycycline for presumed community-acquired pneumonia. He returned to the emergency room 1 week later with mild hypoxemia, persisting fever, and a chest radiography consistent with lobar pneumonia. The patient was admitted to his local community hospital, and broad-spectrum antibiotics were added to the regimen. Unfortunately, his condition deteriorated over the following week, and he experienced hypoxic respiratory failure for which he required mechanical ventilation before his transfer to our medical center.

Extreme Hyponatremia Complicated by Osmotic Demyelination in a Previously Healthy Young Individual.

Rationale: Severe hyponatremia can lead to dramatic complications whether it is treated or not. At times, it may be very severe (serum Na concentration: NaS < 115 mmol/L) or even extreme (NaS < 105 mmol/L)a and its cause difficult to identify, especially in younger individuals with no history of water disorders. The case presented herein illustrates these points quite eloquently and leads us to believe that the current recommendations for the treatment of very severe hyponatremia require some fine-tuning. Presenting Concerns: A 26-year-old man was admitted to our intensive care unit for a NaS of 88 mmol/L in the absence of obvious extracellular fluid volume contraction. He had been experiencing vomiting, diarrhea, fatigue, and excessive thirst for the past 6 weeks and minor neurological symptoms just before admission. Laboratory tests at presentation also showed a urine osmolarity of 697 mOsm/L and urine Na of 40 mmol/L. Diagnoses: The presenting concerns were consistent with syndrome of inappropriate antidiuretic hormone secretion (SIADH) manifesting as extreme, yet mildly symptomatic hyponatremia. At the same time, they did not point toward a specific cause initially. Interventions: The patient was treated through water restriction, subcutaneous desmopressin, and various intravenous (IV) fluids. Our goal had been to increase NaS at a rate of 4 to 6 mmol/L/day and required the amount of NaCl and free water perfused hourly to be readjusted constantly. Access to water also had to be opposed as the patient was unable to tolerate his thirst. Outcomes: During the first 6 days, the rate of NaS correction achieved was ~6 mmol/L/day. The patient improved initially but at the end of day 6, he experienced severe extrapontine osmotic demyelination (with widespread pyramidal and extrapyramidal deficits) that did not respond to intravenous immunoglobulin and NaS relowering. A little more than 3 weeks later, he began to develop low blood pressure and a subfebrile state that revealed secondary to severe Addison disease. The water disorder and insatiable thirst subsided gradually upon replacing the deficient hormones but the neurological disorder went on to become permanent and highly disabling. Teaching points: (1) Very severe hyponatremia should always be handled as an emergency and monitored stringently in view of its potential to cause irreparable damage. (2) Because it is a major risk factor for osmotic demyelination, it should probably be corrected at a rate of less than 4 mmol/L/day especially if it is in the extreme range, chronic, or of unknown duration. (3) It can be a presenting manifestation of Addison disease.

Justification: Qu'elle soit traitée ou non, l'hyponatrémie grave peut entraîner des complications dramatiques. L'hyponatrémie peut être très grave (concentration de Na sérique : NaS < 115 mmol/L), voire extrême (NaS < 105 mmol/L)a, et sa cause peut être difficile à identifier, particulièrement chez les sujets plus jeunes sans antécédents de déséquilibres hydriques. Le cas présenté illustre ces points de façon éloquente et nous porte à croire que les recommandations actuelles pour le traitement de l'hyponatrémie très grave nécessitent un ajustement. Présentation du cas: Un homme de 26 ans a été admis à notre unité de soins intensifs pour une NaS de 88 mmol/L sans contraction évidente du volume liquidien extracellulaire. Le patient avait souffert de vomissements, de diarrhée, de fatigue et de soif excessive au cours des six dernières semaines, et de symptômes neurologiques mineurs juste avant son admission. Les analyses de laboratoire à la présentation montraient également une osmolarité urinaire à 697 mOsm/L et une concentration de Na urinaire à 40 mmol/L. Diagnostic: Les symptômes à la présentation étaient compatibles avec un SIADH se manifestant par une hyponatrémie extrême, bien que peu symptomatique. En même temps, ces symptômes ne pointaient pas initialement vers une cause spécifique. Intervention: Le patient a été traité par restriction liquidienne, desmopressine SC et divers liquides administrés par voie intraveineuse. L'objectif était d'augmenter la NaS entre 4 et 6 mmol/L/jour et il a requis que la quantité de NaCl et d'eau libre perfusée toutes les heures soit réajustée en permanence. L'accès à l'eau a également dû être restreint, car le patient était incapable de tolérer sa soif. Résultats: Au cours des six premiers jours, la correction atteinte pour la NaS "était" par "a été" d'environ 6 mmol/L/jour. L'état du patient s'est d'abord amélioré, mais à la fin du 6e jour, il a évolué vers une démyélinisation osmotique extrapontine sévère (avec déficits pyramidaux et extrapyramidaux étendus) qui n'a pas répondu à l'administration d'IVIG ni à la diminution de la NaS. Un peu plus de trois semaines plus tard, le patient a présenté une hypotension et a développé un état subfébrile qui se sont révélés secondaires à une maladie d'Addison sévère. Le déséquilibre hydrique et la soif insatiable se sont résorbés progressivement après le remplacement des hormones déficientes, mais les le désordre neurologique est devenu permanent et très invalidant. Enseignements tirés: 1) L'hyponatémie très grave devrait toujours être traitée comme une urgence et surveillée de façon continue en raison de son potentiel à causer des dommages irréversibles. 2) Parce qu'elle est un facteur de risque majeur pour la démyélinisation osmotique, l'hyponatrémie devrait probablement être corrigée à un taux inférieur à 4 mmol/L/jour, surtout si elle est jugée extrême, chronique ou de durée inconnue. 3) L'hyponatrémie peut être un symptôme inaugural de la maladie d'Addison.

An unusual isolated anterior mediastinal lesion.

Malignant pleural mesothelioma (MPM) is an infrequent tumour of poor prognosis with a strong association with asbestos exposure. Pleural effusion or thickening is the most common radiological finding. Thoracoscopic biopsy is the diagnostic modality of choice. In our report, we present the case of a career welder who consulted with vocal cord palsy and an atypical anterior mediastinal lesion. An EBUS-TBNA-guided biopsy and a thorough cytological assessment led to an unexpected diagnosis of epithelioid MPM. A localized anterior mediastinal lesion is an extremely infrequent presentation of MPM that deserves clinical recognition.

Malignant pleural mesothelioma: Comparison of surgery-based trimodality therapy to medical therapy at two tertiary academic institutions.

OBJECTIVES: Medical management based on palliative chemotherapy is currently the standard of care in malignant pleural mesothelioma (MPM). Median survival of 12-16 months has been reported with modern chemotherapy regimens with or without anti-angiogenic agents. Multimodality therapy incorporating cytoreductive surgery, systemic chemotherapy and radiotherapy has been offered for years to fit patients with early-stage disease, but its role remains debated. Our objective was to compare overall survival in patients offered multimodality therapy in a specialized clinic setting in London, UK to that of patients offered exclusively medical treatment at another academic institution in Quebec, Canada. MATERIALS AND METHODS: We retrospectively compared the survival rates of 2 separate cohorts of patients treated consecutively: Cohort 1 (n = 106) received multimodality therapy including systemic chemotherapy, extended pleurectomy/decortication (P/D) and prophylactic radiotherapy in London (United Kingdom) between 2009 and 2016, while Cohort 2 (n = 98) received medical treatment at the Quebec Heart and Lung Institute (Canada) during the same period. RESULTS: In Cohort 1, all patients but two completed trimodality therapy. In cohort 2, 51 % received palliative care only and 40 % received systemic chemotherapy. Median survival was 32 months vs 10 months in Cohort 1 and Cohort 2, respectively (hazard ratio with age, gender, pathology and TNM staging as covariates: 3.81; 95 % CI: 2.67-5.45; p < 0.0001). Similar results were obtained in sensitivity analyses, after excluding those who received best supportive care only and in a propensity score-matched analysis. CONCLUSION: Aggressive therapy of MPM using cancer-directed surgery, systemic chemotherapy and prophylactic radiotherapy may provide a significant survival benefit in selected patients.

Aetiology, diagnosis and treatment of moderate-to-severe haemoptysis in a North American academic centre.

Significant haemoptysis is a frightening event for patients and clinicians alike. There is a paucity of contemporary literature on the subject. A retrospective analysis of hospitalisations for haemoptysis of more than 50 mL·day-1 in a tertiary referral centre during a 5-year period was performed. Patient's characteristics, haemoptysis aetiology, management and outcome were individually recorded. The aim of this study was to detail the causes of moderate (50-200 mL·day-1) to severe (>200 mL·day-1) haemoptysis along with the diagnostic measures and treatment options used in their management in a 21st century, tertiary-care North American centre. A total of 165 hospitalisations for moderate-to-severe haemoptysis were included in the analysis. Lung cancer (30.3%) and bronchiectasis (27.9%) proved to be most frequent aetiologies. Computed tomography (CT) imaging and bronchoscopy were complementary in identifying the source of bleeding. Bronchial artery embolisation (BAE) was the most common treatment approach (61.8%) and resulted in initial bleeding control in 73.5% of cases. In-hospital mortality was 13.9%, varying from 3.3% in the moderate group to 24.7% in the severe group. Despite being the favoured approach in patients with more severe bleeding, initial BAE therapy was associated with a trend towards lower mortality compared to initial non-BAE therapy. In summary, lung cancer and bronchiectasis were the main causes of moderate-to-severe haemoptysis in our population, CT and bronchoscopy are complementary in identifying the source of bleeding, bleeding volume is associated with outcomes and BAE is a key management tool.

Approach to Hemoptysis in the Modern Era.

Hemoptysis is a frequent manifestation of a wide variety of diseases, with mild to life-threatening presentations. The diagnostic workup and the management of severe hemoptysis are often challenging. Advances in endoscopic techniques have led to different new therapeutic approaches. Cold saline, vasoconstrictive and antifibrinolytic agents, oxidized regenerated cellulose, biocompatible glue, laser photocoagulation, argon plasma coagulation, and endobronchial stents and valves are amongst the tools available to the bronchoscopist. In this article, we review the evidence regarding the definition, etiology, diagnostic modalities, and treatment of severe hemoptysis in the modern era with emphasis on bronchoscopic techniques.