The Effect of Extreme Alkalemia upon Presentation to the Emergency Department on Patient Outcomes.

Background/Objectives: The prognostic significance of alkalemia found in an initial emergency department (ED) evaluation has not been described thus far. Methods: We retrospectively reviewed the records of all patients aged 18 years or older evaluated in the ED of one large academic referral center during 2000-2023. Included patients were those with at least one measurement of pH ≥ 7.55 upon initial ED presentation. Alkalemia was deemed primarily metabolic (PM) if PCO2 was ≥35 mmHg and primarily respiratory (PR) if bicarbonate levels were ≤24 mEq/L. The primary outcome was survival 30 days from ED presentation. Results: Of 2440 patients included, 199 (8.1%) had PM and 1494 (61.2%) had PR. Alkalemia severity was not correlated with prognosis. Survival at 30 days was significantly (p < 0.001) lower in the PM group (78.9%) compared with that of either the PR (95.3%) or the combined etiology (92.2%) groups. Multivariate survival analysis after balancing potential observed confounders using propensity score matching revealed the type of alkalemia (PM vs. PR) to be a significant predictor of 30-day mortality (aHR 1.73; 95% C.I. = [1.07 to 2.82]; p = 0.026), irrespective of age, other laboratory values obtained on ED evaluation (including pH), past medical history, or vital signs on presentation. Conclusions: In patients presenting to the ED with significant alkalemia, the mechanism of alkalemia, i.e., primarily metabolic versus primarily respiratory, rather than the absolute degree of alkalemia, is associated with increased mortality.

Impact of discontinuing routine fluoroquinolone prophylaxis in neutropenic allogeneic haematopoietic stem cell transplant recipients: an observational study.

BACKGROUND: Uncertainty exists as to the role of fluoroquinolone (FQ) prophylaxis for patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) in the era of rising antibiotic resistance. OBJECTIVES: We aimed to evaluate rates of bloodstream infections (BSI), resistance patterns and outcomes of patients after discontinuing routine FQ prophylaxis administration. METHODS: All adult recipients of first HSCT from 2017 to 2020 were retrospectively included and classified according to time of HSCT as FQ group (HSCT January 2017-December 2018) or no FQ group (January 2019-December 2020). The primary outcome was Gram-negative (GN) BSI from day -7 to 30 days post-HSCT. The independent association between the study period and BSI was assessed using survival analysis, and adjusting for confounders. RESULTS: We included 254 patients, 130 (51%) and 124 (49%) in the FQ and no FQ groups, respectively. Compared to the FQ group, no FQ had significantly more GN BSI (21% versus 33%, P = 0.027) and the median time to first GN BSI was significantly shorter [4 (IQR 1-8) days versus 6 (1-10) days, P = 0.009]. Following adjustment, FQ prophylaxis remained associated with lower hazard for GN BSI (hazard ratio 0.57, 95% CI 0.34-0.93). Eighty-two GN BSI episodes had FQ susceptibility testing. More GN BSI episodes were FQ resistant in the FQ group (68.9% versus 41.6%, P = 0.021). No significant difference was found for 30-day mortality, time to first febrile neutropenia and time to first broad-spectrum antibiotics between the groups (P was not significant). CONCLUSIONS: FQ prophylaxis is associated with fewer GN BSI in the early post-HSCT period even in high FQ resistance settings, with FQ resistance rates reaching >60% following prophylaxis.

Methylphenidate and the risk of acute central nervous system oxygen toxicity: a rodent model and observational data in human divers.

Introduction: The effects of methylphenidate, a stimulant often prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD), on the development of central nervous system oxygen toxicity (COT) have not been experimentally evaluated. Methods: The records of all pure-oxygen-rebreather divers evaluated at our institution from 1975-2022 were assessed. Cases of COT were defined as a new onset of tinnitus, tunnel vision, myoclonus, headache, nausea, loss of consciousness, or seizures resolving within 15 minutes from breathing normobaric air, and matched 4:1 with similar controls. Any medications issued to the diver in the preceding three months, including methylphenidate, were recorded. In the animal arm of this study, male mice were exposed to increasing doses of methylphenidate orally, with subsequent exposure to hyperbaric O2 until clinically evident seizures were recorded. Results: Seventy-five cases of COT were identified in divers, occurring at a median of 80 (range 2-240) minutes after dive initiation at a median depth of 5 m (2-13). Hypercarbia was documented in 11 (14.7%) cases. Prescription of methylphenidate in the preceding three months was not associated with increased risk (OR 0.72, 95% CI 0.16-3.32) of COT. In mice, increasing methylphenidate exposure dose was associated with significantly longer mean COT latency time being 877 s (95% CI 711-1,043) with doses of 0 mg·kg⁻¹; 1,312 s (95% CI 850-1,773) when given 0.75 mg·kg⁻¹; and 1,500 s (95% CI 988-2,012) with 5 mg·kg⁻¹ (F = 4.635, P = 0.014). Conclusions: Observational human data did not demonstrate an association between methylphenidate and an increased risk of COT. Methylphenidate exposure in mice prolongs COT latency and may have protective effects against COT.

Clinical impact of fungal colonization of burn wounds in patients hospitalized in the intensive care unit: a retrospective cohort study.

Background: Invasive fungal infections in burn victims significantly increase mortality and hospitalization. The effect of fungal burn wound colonization has not been established. Methods: All adult patients hospitalized in the intensive care unit (ICU) with burns ≥10% of total body surface area (TBSA) between 2005 and 2021 were included. Superficial swabs were collected whenever clinical suspicion of wound colonization was raised, and deep tissue samples were sent at any wound excision. The primary outcome was the incidence of invasive fungal infections defined as any deep tissue fungal infection or fungemia. Results: Of 242 patients included, 39 (16.1%) had fungal wound colonization, 22 (56.4%) with yeasts and 24 (61.5%) molds. Patients with fungal colonization had a significantly higher rate of invasive fungal infections (82.1% vs 3.9%, p<0.001), candidemia (15.4% vs 3.4%, p=0.002), as well as longer ICU stay (61.5±57.6 vs 19±40.5 days, p<0.001), and higher in-ICU mortality (43.6% vs 15.8%, p<0.001). Survival analysis showed fungal colonization to be associated with significantly increased risk of invasive infection (aHR 25, 95% CI (9.67 to 64.62)), even when adjusted for age, TBSA, sequential organ failure assessment scores, Charlson Comorbidity Index and the presence of bacteremia. Conclusions: Fungal burn wound colonization is associated with increased risk of invasive fungal infections and mortality. Level of Evidence: This a single center, retrospective cohort study.

Safety of Bronchoalveolar Lavage in Hematological Patients with Thrombocytopenia. A Retrospective Cohort Study.

Background: Hospitalized hematological patients often require bronchoalveolar lavage (BAL). Scarce evidence exists regarding the potential risks in patients with very severe thrombocytopenia (VST). Methods: This retrospective-cohort study included adult hematological in-patients with VST, defined as platelets<20x103/µL, undergoing BAL during 2012-2021. Mechanically ventilated patients or those with known active bleeding were excluded. Primary outcomes included major bleeding halting the BAL or deemed significant by the treating physician, need for any respiratory support other than low flow O2, or death within 24 hours. Any other bleedings were recorded as secondary outcomes. Results: Of the 507 patients included in the final analysis, the 281 patients with VST had lower hemoglobin (Md=0.3, p=0.003), longer prothrombin-time (Md=0.7s, p=0.025), higher chances of preprocedural platelet transfusion (RR 3.68, 95%CI [2.86,4.73]), and only one primary-outcome event (death of septic shock 21h postprocedurally) - compared with 3 (1.3%) events (two bleedings halting procedure and one need for non-invasive-ventilation) in patients with platelets ≥20x103/µL (p=0.219). The risk of minor spontaneously resolved bleeding was higher (RR=3.217, 95% CI [0.919,11.262]) in patients with VST (4.3% vs 1.3%, p=0.051). No association was found between the complications recorded and preprocedural platelets, age, aPTT, P.T., hematological status, or platelet transfusion. Conclusions: This data suggests BAL to be safe even when platelet counts are <20x103/µL.

Combining reservoir mask oxygenation with high-flow nasal cannula in the treatment of hypoxemic respiratory failure among patients with COVID-19 pneumonia: a retrospective cohort study.

BACKGROUND: Concerns regarding positive-pressure-ventilation for the treatment of coronavirus disease 2019 (COVID-19) hypoxemia led the search for alternative oxygenation techniques. This study aimed to assess one such method, dual oxygenation, i.e., the addition of a reservoir mask (RM) on top of a high-flow nasal cannula (HFNC). METHODS: In this retrospective cohort study, the records of all patients hospitalized with COVID-19 during 2020-2022 were reviewed. Patients over the age of 18 years with hypoxemia necessitating HFNC were included. Exclusion criteria were positive-pressure-ventilation for any indication other than hypoxemic respiratory failure, transfer to another facility while still on HFNC and "do-not-intubate/resuscitate" orders. The primary outcome was mortality within 30 days from the first application of HFNC. Secondary outcomes were intubation and admission to the intensive care unit. RESULTS: Of 659 patients included in the final analysis, 316 were treated with dual oxygenation and 343 with HFNC alone. Propensity for treatment was estimated based on background diagnoses, laboratories and vital signs upon admission, gender and glucocorticoid dose. Inverse probability of treatment weighted regression including age, body mass index, Sequential Organ Failure Assessment (SOFA) score and respiratory rate oxygenation index showed treatment with dual oxygenation to be associated with lower 30-day mortality (adjusted hazard ratio, 0.615; 95% confidence interval, 0.469-0.809). Differences in the secondary outcomes did not reach statistical significance. CONCLUSIONS: Our study suggests that the addition of RM on top of HFNC may be associated with decreased mortality in patients with severe COVID-19 hypoxemia.

Dual Oxygenation in the Treatment of Hypoxemic Respiratory Failure: A Retrospective Cohort Study.

BACKGROUND: At the beginning of the coronavirus disease 2019 (COVID-19) pandemic, many patients presented with acute hypoxemic respiratory failure, requiring ventilatory support. One treatment method was the addition of a reservoir mask to a high flow nasal cannula (HFNC) (dual oxygenation). OBJECTIVES: To evaluate the clinical outcomes of combining reservoir mask on top of a high-flow nasal cannula. METHODS: A retrospective cohort of adult patients who were admitted due to COVID-19 during the first year of the pandemic to Rambam Health Care Campus. The primary endpoint was 30-day mortality. Secondary endpoints were incidence of invasive positive pressure ventilation initiation and admission to the intensive care unit (ICU). Patients who received positive pressure ventilation for reasons other than hypoxemic respiratory failure or who were transferred to another facility while still on HFNC were excluded. RESULTS: The final analysis included 333 patients; 166 were treated with dual oxygenation and 167 with HFNC only (controls). No significant differences in baseline characteristics were noted between the groups. The dual oxygenation group was slightly older (69.2 ± 14.8 years vs. 65.6 ± 15.5 years, P = 0.034). The 30-day mortality (24.1% vs. 36.5%, P = 0.013), rates of invasive positive pressure ventilation (47% vs. 59.3%, P = 0.024), and ICU admissions (41.6% vs. 52.7%, P = 0.042) were all significantly lower in the dual oxygenation group. CONCLUSIONS: The addition of reservoir masks to HFNC may improve the oxygenation and overall prognosis in patients with severe hypoxemia due to COVID-19.

Clinical presentations of acute pulmonary embolism: A retrospective cohort study.

We aimed to investigate whether the unusual clinical presentation of pulmonary embolism (PE) varies by the type of provocation. In this retrospective cohort study, we examined the electronic health records (EHR) records of all patients diagnosed with PE (upon presentation or during hospitalization) presented to our tertiary hospital during 2014 to 2019. Inclusion criteria were the diagnosis of acute PE and age above 18 years. Excluded were all patients to whom complete EHR were not available. The primary outcome was the main presenting symptom, categorized by a multidisciplinary consensus expert committee as either typical or atypical of PE. Comorbidities, vital signs, medications and laboratory results on presentations were recorded. 591 patients were included in the final analysis. Dyspnea was significantly less common and hemoptysis and chest pain more common in the unprovoked PE group (35%, 5%, and 25%, respectively) compared with nonmalignant (42.6%, 0%, and 16.3%) and malignancy-associated (47.7%, 0.9%, and 8.2%) PE (Pv = 0.02, 0.002 and 0.001, respectively). No recorded symptoms were the third most common presentation overall, accounting for a significantly (Pv < 0.001) higher proportion of PE patients with malignancy (19%) whereas atypical presentation was the hallmark of patients with nonmalignant provokation (19.7%) (Pv = 0.005). Accounting for multiple potential confounders, the risk of atypical or asymptomatic presentation was higher with lower heart rates (RR = 0.974 95%C.I. [0.957-0.990]) and higher pulse oximetry saturation (RR = 1.114 95%CI [1.034-1.201]). The clinical presentation of PE varies with different types of provoking factors, with atypical presentation most common in nonmalignant provocation and asymptomatic presentation most prevalent in patients with underlying malignancy. Further studies are needed to determine the effect of said variance on long term clinical outcomes.

Implementing Lean Techniques to Increase the Efficiency of a Rural Primary Care Clinic: A Prospective Controlled Study.

BACKGROUND: Lean, a management approach focused on identifying and eliminating waste, has been proposed as a solution for shortages in health care. Many studies implementing Lean in health care have lacked adequately designed controls. METHODS: This was a prospective, block randomized, controlled study conducted in a single primary care clinic comprising three primary care providers. A multidisciplinary team constructed a value stream, proposing foci of waste and possible solutions. These were implemented during three consecutive eight-week blocks. A sample was taken of 40 random visits for each physician during each block, and one physician was randomized to implement the interventions while the other two served as controls. RESULTS: Intervention blocks were significantly shorter compared to control blocks, with a mean difference (MD) of -1,190 seconds (s) (95% confidence interval = 1,039-1,342, p < 0.001). This was primarily the result of four interventions: (1) relocating the printer to the front desk (MD -378 s, p < 0.001), (2) adding another parallel working station (MD -258 s uploading the patient's file and MD -138 s uploading the history, p < 0.001 for both), (3) documenting in plain typing (MD -229 s, p < 0.001), and (4) rerouting delayed patients to the next available physician (MD -195 s, p = 0.004). Two steps were modestly lengthened: anamnesis (MD 24 s, p < 0.001) and explaining the diagnosis and treatment plan (MD 11 s, p = 0.001). Average productivity was increased by 1.65 appointments per hour (p < 0.001). Burnout scores decreased from an average of 74 points during control blocks to 63.8 on intervention (p < 0.01). No clinically or statistically significant difference was noted in quality of care, definitivity of treatment, or patient satisfaction (p = 0.83, 0.55, and 0.77, respectively). CONCLUSION: Intrinsically led, multidisciplinary Lean implementation in a rural primary care clinic dramatically shortened the value stream duration, while requiring no extrinsic resources. Widening Lean implementation and research in primary care, particularly in rural settings, may increase the availability and effectiveness of primary care.

COVID-19 in Patients with Hematologic Malignancies: Clinical Manifestations, Persistence, and Immune Response.

BACKGROUND: The clinical presentation of coronavirus disease 19 (COVID-19) is the result of intricate interactions between the novel coronavirus and the immune system. In patients with hematologic malignancies (HM), these interactions dramatically change the clinical course and outcomes of COVID-19. SUMMARY: Patients with HM and COVID-19 are at an increased risk for prolonged viral shedding, more protracted and severe presentation, and death, even when compared to other immunocompromised hosts. HM (e.g., multiple myeloma, chronic lymphocytic leukemia) and anticancer treatments (e.g., anti-CD20 agents) that impair humoral immunity markedly increase the risk of severe COVID-19 as well as protracted viral shedding and possibly longer infectivity. Cytokine release syndrome (CRS) is an important player in the pathophysiology of severe and fatal COVID-19. Treatments targeting specific cytokines involved in CRS such as interleukin-6 and Janus kinase have proven beneficial in COVID-19 patients but were not assessed specifically in HM patients. Although neutropenia (as well as neutrophilia) was associated with increased COVID-19 mortality, granulocyte colony-stimulating factors were not beneficial in patients with COVID-19 and may have been associated with worse outcomes. Decreased levels of T lymphocytes and especially decreased CD4+ counts, and depletion of CD8+ lymphocytes, are a hallmark of severe COVID-19, and even more so among patients with HM, underlying the important role of T-helper dysfunction in severe COVID-19. In HM patients with intact cellular immunity, robust T-cell responses may compensate for an impaired humoral immune system. Further prospective studies are needed to evaluate the mechanisms of severe COVID-19 among patients with HM and assess the efficacy of new immunomodulating COVID-19 treatments in this population. KEY MESSAGES: Understanding the immunopathology of COVID-19 has greatly benefited from the previous research in patients with HM. So far, no COVID-19 treatments were properly evaluated in patients with HM. Patients with HM should be included in future RCTs assessing treatments for COVID-19.

Immune reconstitution inflammatory syndrome (IRIS) in a patient with neuro pulmonary nocardiosis following hematopoietic cells transplantation (HCT).

Immune reconstitution inflammatory syndrome (IRIS) is increasingly reported in various HIV negative patients with immunosuppression, but the relationship with hematopoietic cell transplantation (HCT) is not well defined. We report a case of IRIS in a patient infected with pulmonary and CNS Nocardiosis following HCT due to primary myelofibrosis.

[IMPLEMENTING AMBULATORY BLOOD PRESSURE MONITORING (ABPM) IN THE PRIMARY CLINIC].

BACKGROUND: Hypertension (HTN) is the leading reversible risk factor for cardiovascular morbidity and all-cause mortality. Screening is currently based on office blood pressure measurement (OBPM) - a method that is neither sensitive nor specific in detecting true HTN. Home blood pressure monitoring, which is often used to confirm and follow-up the diagnosis of HTN, is limited in its ability to detect certain blood pressure (BP) patterns that are harmful, and not covered by Israeli health insurers. Over the last two decades, the alternative and gold standard - 24 hours ambulatory blood pressure monitoring (ABPM) has become cheap and easy to use, but it is virtually nonexistent in primary care clinics. METHODS: This research aims to assess the clinical and distributional benefits of operating an ABPM in the primary clinic, without utilising any additional external resources besides the ABPM monitor, which was borrowed for this purpose from the regional Israeli Defense Force's Medical Corps (IDFMC) health-care center. All service-members in a medium sized Israeli Air Force (IAF) airbase were screened for HTN using OBPM. Inclusion criteria were BP over 130/85 at least once during the past two years or a personal or family history of HTN. Exclusion criteria were any antihypertensive medication taken over the past 6 months, renal dysfunction or secondary HTN. RESULTS: A total of 2167 patients were screened, of whom 64 (2.9%) met selection criteria. Of these, 56 (87.5%) responded to our invitation and performed full OBPM on three separate occasions. During an 8 weeks long lease 46 of 47 (96.4%) available slots were utilized - 2.19 times more efficient than the regional clinic average utilization rate. Of 18 patients who have been diagnosed with HTN in the past, 13 (72.2%) met the criteria on OBPM but only 6 (46.1%) of these were confirmed as having HTN on ABPM. The positive predictive value (PPV) of abnormally high BP on OBPM for the diagnosis of HTN on ABPM averaged 41.3%. The negative predictive value (NPV) of normal OBPM was 80% and 83.4%, for patients diagnosed in the past with HTN or having risk factors (obesity and family history), respectively. CONCLUSIONS: The therapeutic, prognostic and economic implications of the diagnosis of HTN necessitate the utilization of an accurate diagnostic tool. Recent advancements, making ABPM affordable and easy to use, combined with the immediate and dramatic clinical implications witnessed when ABPM was used in our clinic, necessitate a closer look at the need to make ABPM available at the primary clinic.