Acetazolamide and Hydrochlorothiazide in Patients With Acute Decompensated Heart Failure: Insights From Recent Trials.

Acetazolamide and thiazide diuretics have been combined with loop diuretics to overcome diuretic resistance in heart failure patients. However, recent studies have assessed the upfront combination of acetazolamide and hydrochlorothiazide with loop diuretics in hospitalized patients with acute decompensated heart failure without loop diuretic resistance. We reviewed two recent randomized controlled trials on the upfront use of acetazolamide and thiazide diuretics in acute decompensated heart failure, respectively. When the two trials on acetazolamide are considered together, adding oral or intravenous acetazolamide to loop diuretics in decompensated heart failure patients resulted in increased diuresis and natriuresis. However, the effects were significantly higher in patients with serum bicarbonate ≥ 27 mmol/L and those with higher baseline glomerular filtration rate (GFR). Similarly, when the two trials on thiazide diuretics are considered together, adding hydrochlorothiazide to loop diuretics in decompensated heart failure patients resulted in increased diuresis and weight loss. However, it increases the risk of impaired renal function. When all the trials are considered together, the upfront use of acetazolamide may be helpful in carefully selected patients, including patients with underlying elevated bicarbonate levels (≥ 27 mmol/L) and those with good renal function (GFR > 50). Conversely, though the upfront use of thiazide diuretic added to intravenous furosemide improved diuretic response in acute decompensated heart failure, it causes an increased risk of worsening renal function and lack of clear evidence of reducing hospital length of stay.

Remdesivir, dexamethasone and angiotensin-converting enzyme inhibitors use and mortality outcomes in COVID-19 patients with concomitant troponin elevation.

BACKGROUND: There are indications that viral myocarditis, demand ischemia, and renin-angiotensin-aldosterone system pathway activation play essential roles in troponin elevation in coronavirus disease 2019 (COVID-19) patients. Antiviral medications and steroids are used to treat viral myocarditis, but their effect in patients with elevated troponin, possibly from myocarditis, has not been studied. AIM: To evaluate the effect of dexamethasone, remdesivir, and angiotensin-converting enzyme (ACE) inhibitors (ACEI) on mortality in COVID-19 patients with elevated troponin. METHODS: Our retrospective observational study involved 1788 COVID-19 patients at seven hospitals in Southern California, United States. We did a backward selection Cox multivariate regression analysis to determine predictors of mortality in our study population. Additionally, we did a Kaplan Meier survival analysis in the subset of patients with elevated troponin, comparing survival in patients that received dexamethasone, remdesivir, and ACEI with those that did not. RESULTS: The mean age was 66 years (range 20-110), troponin elevation was noted in 11.5% of the patients, and 29.9% expired. The patients' age [hazard ratio (HR) = 1.02, P < 0.001], intensive care unit admission (HR = 5.07, P < 0.001), and ventilator use (HR = 0.68, P = 0.02) were significantly associated with mortality. In the subset of patients with elevated troponin, there was no statistically significant difference in survival in those that received remdesivir (0.07), dexamethasone (P = 0.63), or ACEI (P = 0.8) and those that did not. CONCLUSION: Although elevated troponin in COVID-19 patients has been associated with viral myocarditis and ACE II receptors, conventional viral myocarditis treatment, including antiviral and steroids, and ACEI did not show any effect on mortality in these patients.

Pulmonary Arterial Aneurysms and Thrombosis in a Young Male: A Rare Presentation of Behcet's Disease.

Behcet's disease (BD) is a chronic systemic inflammatory vasculitis with a relapsing and remitting course. The disease predominantly affects males between the ages of 20 and 40 years. The disease is more prevalent in Middle Eastern and Asian countries but is less common in North American countries. BD typically presents as recurrent oro-genital ulcers and ocular inflammation. Pulmonary vasculitis with pulmonary arterial involvement is a unique manifestation, with most pulmonary manifestations occurring later in the disease course. Here, we report a case with pulmonary arterial aneurysms and variable arterial-venous thrombosis in a young African American Male diagnosed with BD after he presented with pulmonary manifestations. This report emphasizes that a high index of suspicion is needed to diagnose a rare condition with such variable manifestations as Behcet's disease and that early detection and immunosuppression therapy can confer improved prognosis.

Bradycardia and Outcomes in COVID-19 Patients on Remdesivir: A Multicenter Retrospective Study.

Background: Antiviral agents, such as remdesivir, have shown promising results in helping reduce the morbidity and healthcare burden of coronavirus disease 2019 (COVID-19) in hospitalized patients. However, many studies have reported a relationship between remdesivir and bradycardia. Therefore, this study aimed to analyze the relationship between bradycardia and outcomes in patients on remdesivir. Methods: We conducted a retrospective study of 2,935 consecutive COVID-19 patients admitted to seven hospitals in Southern California in the United States between January 2020 and August 2021. First, we did a backward logistic regression to analyze the relationship between remdesivir use and other independent variables. Finally, we did a backward selection Cox multivariate regression analysis on the sub-group of patients who received remdesivir to evaluate the mortality risk in bradycardic patients on remdesivir. Results: The mean age of the study population was 61.5 years; 56% were males, 44% received remdesivir, and 52% developed bradycardia. Our analysis showed that remdesivir was associated with increased odds of bradycardia (odds ratio (OR): 1.9, P < 0.001). Patients that were on remdesivir in our study were sicker patients with increased odds of having elevated C-reactive protein (CRP) (OR: 1.03, P < 0.001), elevated white blood cell (WBC) on admission (OR: 1.06, P < 0.001), and increased length of hospital stay (OR: 1.02, P = 0.002). However, remdesivir was associated with decreased odds of mechanical ventilation (OR: 0.53, P < 0.001). In the sub-group analysis of patients that received remdesivir, bradycardia was associated with reduced mortality risk (hazard ratio (HR): 0.69, P = 0.002). Conclusions: Our study showed that remdesivir was associated with bradycardia in COVID-19 patients. However, it decreased the odds of being on a ventilator, even in patients with increased inflammatory markers on admission. Furthermore, patients on remdesivir that developed bradycardia had no increased risk of death. Clinicians should not withhold remdesivir from patients at risk of developing bradycardia because bradycardia in such patients was not found to worsen the clinical outcome.

Meta-analysis and systematic literature review of COVID-19 associated bradycardia as a predictor of mortality.

BACKGROUND: Cardiac arrhythmias have been identified as independent predictors of mortality in Coronavirus disease 2019 (COVID-19) patients. While some studies have reported poor prognosis with bradycardia in COVID-19 patients, others have not found any association between bradycardia and mortality in COVID-19 patients. This study aims to assess the relationship between bradycardia and mortality in COVID-19 patients by reviewing existing literature. MAIN BODY: Articles were obtained by systematically searching the PubMed and Google scholar databases. Qualitative and quantitative analyses of the studies on bradycardia and mortality in COVID-19 were done. A pooled estimate, with a sample size of 1320 patients, comparing the effect of patients that were bradycardic during their admission with those that were not on mortality showed that bradycardia did not lead to increased mortality in COVID-19 patients (OR 1.25, 95% CI 0.41-3.84, p = 0.7). CONCLUSIONS: This meta-analysis showed that bradycardia was not significantly associated with mortality in COVID-19 patients. However, this study is limited by the few studies on bradycardia and mortality in COVID-19 patients. Therefore, future studies should investigate this relationship so that clinicians can prognostically triage and treat COVID-19 patients appropriately.

COVID-19-Related Rhino-Orbito-Cerebral Mucormycosis Complicated by the Optic Nerve and Optic Tract Ischemia With Ischemic Neuropathy.

Mucormycosis is a life-threatening invasive fungal infection usually seen in immunocompromised patients and patients with poorly controlled diabetes mellitus with or without diabetic ketoacidosis. We present a rhino-orbito-cerebral mucormycosis (ROCM) case in a coronavirus disease 2019 (COVID-19) patient complicated by the optic nerve and optic tract ischemia with ischemic neuropathy. Both CT and MRI played an essential role in diagnosing ROCM and the accompanying complications in our patient. CT showed sinonasal sinusitis and MRI showed the sinusitis and its progression to ROCM. MRI also showed necrosis involving the bilateral orbits, basal ganglia, thalamus, internal capsule, hypothalamus, optic chiasm, optic nerves, olfactory bulbs, and skull base. ROCM associated with optic nerve ischemia is a rare but life-threatening complication of COVID-19, especially in patients with underlying diabetes and/or those treated with corticosteroids. Physicians should be aware of this complication as early diagnosis may improve the chances of survival in such patients.

Living with liver disease in the era of COVID-19-the impact of the epidemic and the threat to high-risk populations.

The cardinal symptoms of severe acute respiratory syndrome coronavirus 2 infection as the pandemic began in 2020 were cough, fever, and dyspnea, thus characterizing the virus as a predominantly pulmonary disease. While it is apparent that many patients presenting acutely to the hospital with coronavirus disease 2019 (COVID-19) infection have complaints of respiratory symptoms, other vital organs and systems are also being affected. In fact, almost half of COVID-19 hospitalized patients were found to have evidence of some degree of liver injury. Incidence and severity of liver injury in patients with underlying liver disease were even greater. According to the Centers of Disease Control and Prevention, from August 1, 2020 to May 31, 2022 there have been a total of 4745738 COVID-19 hospital admissions. Considering the gravity of the COVID-19 pandemic and the incidence of liver injury in COVID-19 patients, it is imperative that we as clinicians understand the effects of the virus on the liver and conversely, the effect of underlying hepatobiliary conditions on the severity of the viral course itself. In this article, we review the spectrum of novel studies regarding COVID-19 induced liver injury, compiling data on the effects of the virus in various age and high-risk groups, especially those with preexisting liver disease, in order to obtain a comprehensive understanding of this disease process. We also provide an update of the impact of the new Omicron variant and the changing nature of COVID-19 pathogenesis.

Septic Portal Vein Thrombosis, Clinical Presentation, and Management.

Pylephlebitis, otherwise known as septic portal vein thrombosis, is an infective suppurative thrombosis of the portal vein and/or its intra-hepatic branches. It is a diagnosis that is frequently missed but easily treated with antibiotics. Therefore, it should be considered early on in any patient presenting with fever, abdominal pain, leukocytosis, and evidence of portal vein thrombosis on a CT scan. In this case report, we discuss a case of pylephlebitis as well as the etiologies, diagnosis, and treatment of septic portal vein thrombosis.

Elevated Adrenocorticotropic Hormone, Hypercortisolism, and Marked Hypernatremia.

We present a case of refractory hypernatremia in a patient with elevated adrenocorticotropic hormone (ACTH) and hypercortisolism. Cortisol's effect in tissues results in various outcomes, from maintaining blood pressure to increasing serum glucose levels. In addition, cortisol, cortisone, and aldosterone activate mineralocorticoid receptors with the same affinity; therefore, the activation of mineralocorticoid receptors by elevated cortisol levels leads to increased sodium reabsorption, increased potassium secretion, and metabolic alkalosis. Hypernatremia in our patient was initially refractory to fluid replacement but was eventually corrected with intravenous fluid and desmopressin. Overall, we suggest that hypercortisolism should be considered a differential diagnosis in hypernatremia refractory to fluids replacement.

Leucocytoclastic Vasculitis, Cryoglobulinemia, or Plasma Cell Leukemia: A Diagnostic Conundrum.

Plasma cell leukemia is rare and could be life-threatening. Even rarer and equally life-threatening is cryoglobulinemia. Both of them occurring together paints a grim clinical picture. We present the case of a 63-year-old male with plasma cell leukemia complicated by cryoglobulinemia with skin lesions. The report briefly reviews the clinical and diagnostic characteristics of plasma cell leukemia and well as available treatment options. It also highlights the need to consider non-chemotherapy-based regimens and clinical trials in the care of plasma cell leukemia patients.

Home telemonitoring in heart failure patients and the effect of study design on outcome: A literature review.

INTRODUCTION: A wide range of study designs have been utilized in evaluations of home telemonitoring and these studies have produced conflicting outcomes over the years. While some of the research has shown that telemonitoring is beneficial in reducing all-cause mortality, hospital admission, length of stay in hospital and emergency room visits, other studies have not shown such benefits. This study, therefore, aims to examine several home telemonitoring study designs and the influence of study design on study outcomes. METHOD: Articles were obtained by searching PubMed database with the term heart failure combined with the following terms: telemonitoring, telehealth, home monitoring, and remote monitoring. Searches were limited to randomized controlled trial conducted between year January 1, 2000 and February 6, 2021. The characteristics of the study designs and study outcomes were extracted and analyzed. RESULT: Our review of 34 randomized controlled trials of heart failure telemonitoring did not show any significant influence of study design on reduction in number of hospitalizations and/or decrease in mortality. Studies that were done outside North America (USA and Canada) and studies that selected patients at high risk of re-hospitalization were more likely to result in decreased hospitalization and/or mortality, though this was not statistically significant. All the studies that met our inclusion criteria were from high-income countries and only one study enrolled patients at high risk of re-hospitalization. CONCLUSION: There is a need for more studies to understand why telemonitoring studies in Europe were more likely to reduce hospital admission and mortality compared to those in North America. There is also a need for more studies on the effect of telemonitoring in patients at high risk of hospital readmission.

Public reporting on pharmaceutical industry-led access programs: alignment with the WHO medicine programs evaluation checklist.

BACKGROUND: There has been increased demand for greater public accountability and transparency of private sector-led global health partnership programs. This study critically reviews and pilot tests the World Health Organization (WHO) medicine program checklist as a framework for public reporting and assessing of programs. METHODS: We reviewed each question on the WHO checklist for clarity and usability. Next, we pilot tested the subset of checklist questions focused on program assessment. We extracted and analyzed publicly available information on one randomly selected program from each of the 20 largest research-based biopharmaceutical companies. For each program, we assessed whether publicly available information allowed for an assessment of each relevant question in the checklist. RESULTS: Checklist questions fit in four main categories: [1] national health and development plans, needs, capacity, laws and policies; [2] financial, performance, and public accountability; [3] risk management and mitigation strategies; and [4] long-term sustainability. Nearly all (21 of 22) questions in the checklist require information best provided by companies; one question requires information best provided by governments.Programs frequently reported on the public health needs of their programs (100%), program objectives and activities (100%) and the actual or expected program outputs (95%). There was less information on program alignment with country plans and capacity (50%), detailed program monitoring and evaluation plan (20%), risks mitigation strategies (5%), program needs assessment (5%), and additional resources required from or contributed by government (0%). CONCLUSION: The WHO checklist of key considerations for evaluating proposals for access to medicine programs could be a useful framework for public reporting of program information as most of checklist questions ask for data that should be available to those leading the program. Further revisions of the WHO checklist will help refine it to improve clarity and content validity.

The survival of patients enrolled in a global direct-to-patient cancer medicine donation program: The Glivec International Patient Assistance Program (GIPAP).

BACKGROUND: The Glivec International Patient Assistance Program (GIPAP) is a unique direct-to-patient program that provides imatinib (Glivec) at no cost to eligible patients in low- and middle-income countries (LMICs) with chronic myelogenous leukemia (CML) or gastrointestinal stromal tumor (GIST). This paper analyses the output, outcome and impact of the program between 2001 and 2014 using the data collected by the Max Foundation. METHOD: We extracted data on GIPAP patients' country of residence, sex, diagnosis, date of enrollment in GIPAP, age at enrollment, case closure date, and reason for closure from The Max Foundation database covering the period 2001 to 2014. We used Kaplan-Meier method to assess the survival rate of patients in GIPAP and used the proportional hazard regression model to estimate the effect of different variables on patients' survival. FINDINGS: About 63,000 GIPAP patients in 93 countries received over 71 million defined daily doses (DDD) of imatinib between 2001 and 2014. Our analysis showed that GIPAP patients had a 5-year survival rate of 89% which compares favorably to survival in high income countries despite the challenges of delivering cancer care in LMICs. Age at enrollment into the program, sex, duration between diagnosis and enrollment into program, year of enrollment, and patients' diagnosis (CML vs non-CML) were factors that influenced survival. INTERPRETATION: The GIPAP program has improved the survival of CML and GIST patients in LMICs, most of whom would not have had access to imatinib in the absence of the donation and therapeutic support of the program. FUNDING: This work was funded as part of Access Accelerated case studies. Access Accelerated is an initiative of more than 20 global biopharmaceutical companies in partnership with the World Bank and Union of International Cancer Control that seeks to reduce barriers to prevention, treatment and care for non-communicable diseases in LMICs.

Challenges toward achieving universal health coverage in Ghana, Kenya, Nigeria, and Tanzania.

Although many sub-Saharan African countries have made efforts to provide universal health coverage (UHC) for their citizens, several of these initiatives have achieved little success. This study aims to review the challenges facing UHC in Ghana, Kenya, Nigeria, and Tanzania, and to suggest program or policy changes that might bolster UHC. Routine data reported by the World Bank and World Health Organization, as well as annual reports of the national health insurance schemes of Ghana, Kenya, Nigeria, and Tanzania, were analyzed. The data were supplemented by a review of published and gray literature on health insurance coverage in these four countries. The analysis showed that some of the challenges facing UHC in these countries include (1) large proportion of the population living in extreme poverty and unable to pay premiums, (2) large informal sector whose members are mostly uninsured, (3) high dropout rate from insurance schemes, (4) poorly funded primary health care system, and (5) segmented health insurance fund pool. In order to achieve UHC by 2030, it will be important for these countries to (1) raise sufficient revenue to finance their health systems, (2) improve the efficiency of revenue utilization, (3) identify and provide coverage for the very poor, (4) reduce the proportion of the population that is underinsured, and (5) improve access to quality health care in rural areas.

Identifying the poor for premium exemption: a critical step towards universal health coverage in Sub-Saharan Africa.

Premium exemption for the poor is a critical step towards achieving universal health coverage in sub-Saharan Africa due to the large proportion of the population living in extreme poverty who cannot pay premium. However, identifying the poor for premium exemption has been a big challenge for SSA countries. This paper is a succinct review of four methods available for identifying the poor, outlining the ideal conditions under which each of the methods should be used and the drawbacks associated with using each of the methods.

Inequitable Access to Health Care by the Poor in Community-Based Health Insurance Programs: A Review of Studies From Low- and Middle-Income Countries.

BACKGROUND: Out-of-pocket payments for health care services lead to decreased use of health services and catastrophic health expenditures. To reduce out-of-pocket payments and improve access to health care services, some countries have introduced community-based health insurance (CBHI) schemes, especially for those in rural communities or who work in the informal sector. However, there has been little focus on equity in access to health care services in CBHI schemes. METHODS: We searched PubMed, Web of Science, African Journals OnLine, and Africa-Wide Information for studies published in English between 2000 and August 2014 that examined the effect of socioeconomic status on willingness to join and pay for CBHI, actual enrollment, use of health care services, and drop-out from CBHI. Our search yielded 755 articles. After excluding duplicates and articles that did not meet our inclusion criteria (conducted in low- and middle-income countries and involved analysis based on socioeconomic status), 49 articles remained that were included in this review. Data were extracted by one author, and the second author reviewed the extracted data. Disagreements were mutually resolved between the 2 authors. The findings of the studies were analyzed to identify their similarities and differences and to identify any methodological differences that could account for contradictory findings. RESULTS: Generally, the rich were more willing to pay for CBHI than the poor and actual enrollment in CBHI was directly associated with socioeconomic status. Enrollment in CBHI was price-elastic-as premiums decreased, enrollment increased. There were mixed results on the effect of socioeconomic status on use of health care services among those enrolled in CBHI. We found a high drop-out rate from CBHI schemes that was not related to socioeconomic status, although the most common reason for dropping out of CBHI was lack of money to pay the premium. CONCLUSION: The effectiveness of CBHI schemes in achieving universal health coverage in low- and middle-income countries is questionable. A flexible payment plan where the poor can pay in installments, subsidized premiums for the poor, and removal of co-pays are measures that can increase enrollment and use of CBHI by the poor.

Industry-Led Access-To-Medicines Initiatives In Low- And Middle-Income Countries: Strategies And Evidence.

Global biopharmaceutical companies are increasingly establishing access-to-medicines (AtM) initiatives in low- and middle-income countries. We reviewed the initiatives of twenty-one research-based global biopharmaceutical companies to assess their strategies for improving access and the quality of evidence on the impact of their initiatives. The number of operating initiatives increased from 17 in 2000 to 102 in 2015. Of the 120 different AtM initiatives identified, 48 percent used a medicine donation strategy, and 44 percent used a price reduction strategy. While companies have frequently claimed that their initiatives have had positive impacts, we found published evaluations for only seven initiatives, and nearly all of the evaluations were of low (62 percent) or very low (32 percent) quality. It is clear that the biopharmaceutical industry has increased its commitment to improving access to medicines in low- and middle-income countries. However, companies should do more to generate high-quality evidence on their initiatives, and the global health community should do more to assist the developing of evidence about the initiatives.

Estimating the Burden of Chagas Disease in the United States.

BACKGROUND: In recent years, there has been growing awareness of the significant burden of Chagas disease in the United States (US). However, epidemiological data on both prevalence and access to care for this disease are limited. The objective of this study is to provide an updated national estimate of Chagas disease prevalence, the first state-level estimates of cases of T. cruzi infection in the US and to analyze these estimates in the context of data on confirmed cases of infection in the US blood supply. METHODS: In this study, we calculated estimates of the state and national prevalence of Chagas disease. The number of residents originally from Chagas disease endemic countries were computed using data on Foreign-Born Hispanic populations from the American Community Survey, along with recent prevalence estimates for Chagas disease in Latin America from the World Health Organization that were published in 2006 and updated in 2015. We then describe the distribution of estimated cases in each state in relation to the number of infections identified in the donated blood supply per data from the AABB (formerly American Association of Blood Banks). FINDINGS: The results of this analysis offer an updated national estimate of 238,091 cases of T. cruzi infection in the United States as of 2012, using the same method as was used by Bern and Montgomery to estimate cases in 2005. This estimate indicates that there are 62,070 cases less than the most recent prior estimate, though it does not include undocumented immigrants who may account for as many as 109,000 additional cases. The state level results show that four states (California, Texas, Florida and New York) have over 10,000 cases and an additional seven states have over 5,000 cases. Moreover, since 2007, the AABB has reported 1,908 confirmed cases of T. cruzi infection identified through screening of blood donations. CONCLUSIONS: This study demonstrates a substantial burden of Chagas disease in the US, with state variation that reflects the distribution of at risk Latin American immigrant populations. The study lends important new insight into the distribution of this disease in the US and highlights the need for further research quantifying prevalence and incidence to guide interventions for control of Chagas disease across the US.