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Cureus May 2023Chronic respiratory insufficiency can result from respiratory infections like pneumonia, which can permanently harm the lungs and respiratory system. A 21-year-old...
Chronic respiratory insufficiency can result from respiratory infections like pneumonia, which can permanently harm the lungs and respiratory system. A 21-year-old female patient arrived at our emergency medicine department (ED) complaining of acute lower-limb pain that worsened when she walked. She also reported feeling weak and having an acute, undiagnosed fever that was resolved by taking medicine two days after the day of admission. She was found to have a body temperature of 99.4°F, decreased air entry on the left side of the chest, and diminished bilateral plantar responsiveness. With the exception of a low calcium level and an increased liver function test, her biochemical indicators were normal. The left lung's basal region had fibrosis, and the right lung's hyperplasia served as a compensatory mechanism, according to the chest radiograph and CT scan of the thorax. The patient underwent treatment with intravenous pantoprazole, ondansetron, ceftriaxone, multivitamin supplementation, gabapentin, and tablets of amitriptyline. On Day 7, her lower limb pain had significantly recovered. After an eight-day hospital stay, she was discharged with instructions to follow up with the pulmonary medicine outpatient department (OPD) and the neurology OPD. A well-known occurrence known as compensatory hyperinflation of the lung happens when one lung is severely injured or rendered inoperable, leading the other lung to enlarge to make up for the loss of respiratory function. This case demonstrates the ability of the respiratory system to compensate for significant damage to one of the lungs.
PubMed: 37398719
DOI: 10.7759/cureus.39771 -
Pharmacogenomics and Personalized... 2023Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology... (Review)
Review
Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology guidelines mention the importance of CYP2C19 in PPI metabolism and the influence of genetic variations on variable responses to PPIs, but do not currently recommend the genotyping of prior to prescribing PPIs. There are strong data to support the influence of genetic variations on the pharmacokinetics of PPIs and clinical outcomes. Existing pharmacogenetic guideline recommendations for dose increases focus on and erosive esophagitis indications, but PPIs are also the main therapy for treating GERD. Recent data suggest GERD patients being treated with a PPI may also benefit from genotype-guided dosing. We summarize the literature supporting this contention and highlight future directions for improved management of patients with GERD through precision medicine approaches.
PubMed: 37383676
DOI: 10.2147/PGPM.S371994 -
Cureus May 2023The introduction of immune checkpoint inhibitors has revolutionized cancer treatment. These drugs function by inhibiting the binding of programmed death-1 (PD-1) and its...
The introduction of immune checkpoint inhibitors has revolutionized cancer treatment. These drugs function by inhibiting the binding of programmed death-1 (PD-1) and its ligand, PD-L1, which inhibits the immune response against cancer cells. Nivolumab is a PD-1 inhibitor that specifically targets the PD-1 pathway. The main side effects of these drugs are unpredictable immune-related toxicities that occur when self-reactive T cells are abnormally activated and cause inflammation in various organs. The organs most often affected are the endocrine glands, lungs, skin, and gut. Recognizing and addressing lung inflammation is crucial, particularly in individuals with lung cancer. However, it can be challenging to diagnose due to the distinctive features of their disease and treatment regimen. This case report presents a 66-year-old man with a medical history of hypertension, chronic kidney disease (stage 3A), hypothyroidism, type 2 diabetes mellitus (DM), and transitional cell carcinoma of the bladder with interstitial pneumonitis secondary to nivolumab. The patient presented to the Eisenhower Medical Center, Rancho Mirage, CA, with dyspnea and cough for two weeks. He received methylprednisolone (Solu-Medrol) at 1.0 mg/kg for immune checkpoint inhibitor-induced pneumonitis and was discharged on 1 liter (L)/min home-oxygen therapy along with prednisone 50 mg twice daily (BD) for six weeks, trimethoprim-sulfamethoxazole (Bactrim) DS BD, and pantoprazole (Protonix) 40 mg once daily. Subsequently, nivolumab therapy was discontinued. At his follow-up visit two weeks later, he felt well and did not need oxygen therapy at rest.
PubMed: 37366435
DOI: 10.7759/cureus.39511 -
Frontiers in Pharmacology 2023Pharmacogenetics-informed drug prescribing is increasingly applied in clinical practice. Typically, drug metabolizing phenotypes are determined based on genetic test...
Pharmacogenetics-informed drug prescribing is increasingly applied in clinical practice. Typically, drug metabolizing phenotypes are determined based on genetic test results, whereupon dosage or drugs are adjusted. Drug-drug-interactions (DDIs) caused by concomitant medication can however cause mismatches between predicted and observed phenotypes (phenoconversion). Here we investigated the impact of genotype on the outcome of CYP2C19-dependent DDIs in human liver microsomes. Liver samples from 40 patients were included, and genotyped for *2, *3 and *17 variants. S-mephenytoin metabolism in microsomal fractions was used as proxy for CYP2C19 activity, and concordance between genotype-predicted and observed CYP2C19 phenotype was examined. Individual microsomes were subsequently co-exposed to fluvoxamine, voriconazole, omeprazole or pantoprazole to simulate DDIs. Maximal CYP2C19 activity (V) in genotype-predicted intermediate metabolizers (IMs; *1/*2 or *2/*17), rapid metabolizers (RMs; *1/*17) and ultrarapid metabolizers (UMs; *17/*17) was not different from V of predicted normal metabolizers (NMs; *1/*1). Conversely, *2/*2 genotyped-donors exhibited V rates ∼9% of NMs, confirming the genotype-predicted poor metabolizer (PM) phenotype. Categorizing CYP2C19 activity, we found a 40% concordance between genetically-predicted CYP2C19 phenotypes and measured phenotypes, indicating substantial phenoconversion. Eight patients (20%) exhibited CYP2C19 IM/PM phenotypes that were not predicted by their CYP2C19 genotype, of which six could be linked to the presence of diabetes or liver disease. In subsequent DDI experiments, CYP2C19 activity was inhibited by omeprazole (-37% ± 8%), voriconazole (-59% ± 4%) and fluvoxamine (-85% ± 2%), but not by pantoprazole (-2 ± 4%). The strength of CYP2C19 inhibitors remained unaffected by genotype, as similar percental declines in CYP2C19 activity and comparable metabolism-dependent inhibitory constants (K/K) of omeprazole were observed between CYP2C19 genotypes. However, the consequences of CYP2C19 inhibitor-mediated phenoconversion were different between genotypes. In example, voriconazole converted 50% of *1/*1 donors to a IM/PM phenotype, but only 14% of *1/*17 donors. Fluvoxamine converted all donors to phenotypic IMs/PMs, but *1/*17 (14%) were less likely to become PMs than *1/*1 (50%) or *1/*2 and *2/*17 (57%). This study suggests that the differential outcome of CYP2C19-mediated DDIs between genotypes are primarily dictated by basal CYP2C19 activity, that may in part be predicted by genotype but likely also depends on disease-related factors.
PubMed: 37361233
DOI: 10.3389/fphar.2023.1201906 -
BMC Cardiovascular Disorders Jun 2023Epipericardial fat necrosis (EFN) is a benign and self-limited condition of unknown cause with a good prognosis, usually affecting otherwise healthy patients....
Epipericardial fat necrosis in chest CT and MRI: a case report of an unusual cause of chest pain associated with the initial diagnosis of undifferentiated connective tissue disease.
BACKGROUND
Epipericardial fat necrosis (EFN) is a benign and self-limited condition of unknown cause with a good prognosis, usually affecting otherwise healthy patients. Clinically, it presents with severe acute left pleuritic chest pain, often leading the patient to the Emergency Room (ER).
CASE PRESENTATION
A 23-year-old male, smoker (5 pack-years), was evaluated in the ER due to left pleuritic chest pain, worsening with deep breathing and Valsalva maneuver. It was not associated with trauma and did not present other symptoms. The physical examination was unremarkable. The arterial blood gases while breathing room air and the laboratory tests, including D-dimers and high-sensitivity cardiac Troponin T, were normal. The chest radiograph, electrocardiogram, and transthoracic echocardiogram showed no abnormalities. A computed tomography (CT) pulmonary angiogram showed no signs of pulmonary embolism but depicted at the left cardiophrenic angle a focal 3 cm ovoid-shaped fat lesion with stranding and thin soft tissue margins, consistent with necrosis of the epicardial fat, which was confirmed by magnetic resonance (MRI) of the chest. The patient was medicated with ibuprofen and pantoprazole, with clinical improvement in four weeks. At a two-month follow-up, he was asymptomatic and presented radiologic resolution of the inflammatory changes of the epicardial fat of the left cardiophrenic angle on chest CT. Laboratory tests revealed positive antinuclear antibodies, positive anti-RNP antibody, and positive lupus anticoagulant. The patient complained of biphasic Raynaud's phenomenon initiated five years ago, and a diagnosis of undifferentiated connective tissue disease (UCTD) was made.
CONCLUSIONS
This case report highlights the diagnosis of EFN as a rare and frequently unknown clinical condition, which should be considered in the differential diagnosis of acute chest pain. It can mimic emergent conditions such as pulmonary embolism, acute coronary syndrome, or acute pericarditis. The diagnosis is confirmed by CT of the thorax or MRI. The treatment is supportive and usually includes non-steroidal anti-inflammatory drugs. The association of EFN with UCTD has not been previously described in the medical literature.
Topics: Male; Humans; Young Adult; Adult; Fat Necrosis; Undifferentiated Connective Tissue Diseases; Chest Pain; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Thorax; Pulmonary Embolism
PubMed: 37349709
DOI: 10.1186/s12872-023-03349-x -
Cureus May 2023Proton-pump inhibitors (PPIs) are one of the most prescribed drugs in the world. Although they are remarkably safe, with minimal adverse effects, it has rarely been...
Proton-pump inhibitors (PPIs) are one of the most prescribed drugs in the world. Although they are remarkably safe, with minimal adverse effects, it has rarely been reported as a cause of anaphylaxis. Hence, we report the case of a 69-year-old patient who experienced intravenous pantoprazole-induced anaphylaxis during peribulbar block anesthesia for mechanical vitrectomy.
PubMed: 37292543
DOI: 10.7759/cureus.38738 -
European Journal of Clinical... Aug 2023In a critical care setting, we aimed to identify and solve physico-chemical drug incompatibilities in central-venous catheters considering the staffs' knowledge and...
PURPOSE
In a critical care setting, we aimed to identify and solve physico-chemical drug incompatibilities in central-venous catheters considering the staffs' knowledge and assumptions about incompatibilities.
METHODS
(i) After positive ethical vote, an algorithm to identify incompatibilities was developed and applied. The algorithm was based on KIK database and Stabilis database, the drug label, and Trissel textbook. (ii) A questionnaire was created and used that asked staff for knowledge and assumptions about incompatibilities. (iii) A 4-step avoidance recommendation was developed and applied.
RESULTS
(i) At least one incompatibility was identified in 64 (61.4%) of 104 enrolled patients. Eighty one (62.3%) of 130 incompatible combinations affected piperacillin/tazobactam and in 18 (13.8%) each furosemide and pantoprazole. (ii) 37.8% (n = 14) of the staff members participated in the questionnaire survey (median age: 31, IQR: 4.75 years). The combination of piperacillin/tazobactam and pantoprazole was incorrectly judged to be compatible by 85.7%. Only rarely felt the majority of respondents unsafe in administering drugs (median score: 1; 0, never to 5, always). (iii) In those 64 patients with at least one incompatibility, 68 avoidance recommendations were given, and all were fully accepted. In 44 (64.7%) of 68 recommendations "Step 1: Administer sequentially" was suggested as a avoidance strategy. In 9/68 (13.2%) "Step 2: Use another lumen", in 7/68 (10.3%) "Step 3: Take a break", and in 8/68 (11.8%) "Step 4: Use catheters with more lumens" were recommended.
CONCLUSIONS
Although incompatibilities were common, the staff rarely felt unsafe when administering drugs. Knowledge deficits correlated well with the incompatibilities identified. All recommendations were fully accepted.
Topics: Humans; Adult; Pantoprazole; Critical Care; Piperacillin, Tazobactam Drug Combination; Algorithms; Catheters
PubMed: 37284873
DOI: 10.1007/s00228-023-03509-0 -
Indian Journal of Otolaryngology and... Jun 2023To clinically evaluate the patients of laryngopharyngeal reflux(LPR) and their response to Proton Pump Inhibitors(PPIs) using laryngeal Reflux Symptom Index (RSI) and...
AIM
To clinically evaluate the patients of laryngopharyngeal reflux(LPR) and their response to Proton Pump Inhibitors(PPIs) using laryngeal Reflux Symptom Index (RSI) and Reflux Finding Score (RFS).
METHOD
This prospective observational study was conducted on 128 patients attending the ENT-OPD of VSSIMSAR,Burla,India, who had persistent laryngeal symptoms for more than 2 months.Data was collected using standardized RSI and RFS after taking detailed history and laryngoscopic examination.Patients who were diagnosed of LPR on the basis of their RSI & RFS were subjected to treatment with PPI-Pantoprazole & were called back for follow up at 2nd, 4th and 6th months.Pre and post treatment RSI & RFS were compared using appropriate statistical tests and results with p-value< 0.01 were considered statistically significant.
RESULTS
The overall effect of PPIs on all symptoms & signs of LPR,included in RSI and RFS respectively,is statistically significant except on swallowing (not statistically significant at p <0.01) showing a careful usage of RSI & RFS while diagnosing LPR clinically.Study also elucidated that PPI are effective in relieving symptoms of LPR patients.Evaluating Pearson correlation coefficient,the value of R=0.3717;R2 =0.1382 shows low positive correlation between the RSI & RFS.RSI & RFS are related to each other and any change in the RSI will affect the value of RFI and vice versa.
CONCLUSION
From this study we conclude that LPR is prevalent in age of 28-37 years & has female preponderance.PPIs are effective in treating LPR.Though RSI and RFS are effective and valid parameters for managing LPR cases but have to be used cautiously while interpreting the results.
PubMed: 37275040
DOI: 10.1007/s12070-022-03219-6 -
Saudi Pharmaceutical Journal : SPJ :... Jul 2023Drug recalls may impact treatment plans or access to suitable therapies. Thus, they inadvertently affect treatment outcomes.
INTRODUCTION
Drug recalls may impact treatment plans or access to suitable therapies. Thus, they inadvertently affect treatment outcomes.
OBJECTIVE
We aimed to examine the impact of recalls on patients' safety using pantoprazole-containing products recall as a case study in terms of the occurrence of potential drug-drug interactions (pDDIs).
METHODS
This retrospective study used de-identified electronic health records of adult patients who had a prescription for oral proton pump inhibitors (PPIs) including pantoprazole, esomeprazole, lansoprazole, or omeprazole from April 2020 through September 2021 from a large tertiary care hospital. The study outcome definition was the prevalence of pDDIs in PPIs users before and after the recall date (March 2021). Changes in the prevalence of pDDIs were modeled using interrupted time-series. The rate ratio of pDDIs in the 12 months before and 6 months after the recall was modeled using negative binomial regression.
RESULTS
A total of 1,826 pDDIs were identified, and the median monthly prevalence of pDDI before the recall was 102.5 which increased to 115.5 after the recall. A change in the level of pDDIs occurred immediately after the recall date, followed by a gradual decrease over time. The rate of pDDIs was 69% higher after the recall compared to the baseline (rate ratio 1.69; 95% confidence interval, 0.75-1.91).
DISCUSSION
Recall of pantoprazole-containing products was associated with a higher rate of pDDIs. However, the prevalence of pDDIs gradually decreased over time. We highlight the importance of planning of recall process and coordinating all potential stakeholders to avoid potential harms.Word count: 1450.
PubMed: 37273266
DOI: 10.1016/j.jsps.2023.04.011 -
Thyroid Research Jun 2023One of the common causes of suboptimal control of thyroid stimulating hormone (TSH) in levothyroxine-treated hypothyroidism is coadministration of proton pump inhibitors...
Effect of morning versus night-time administration of proton pump inhibitor (pantoprazole) on thyroid function test in levothyroxine-treated primary hypothyroidism: a prospective cross-over study.
BACKGROUND
One of the common causes of suboptimal control of thyroid stimulating hormone (TSH) in levothyroxine-treated hypothyroidism is coadministration of proton pump inhibitors (PPIs). Morning administration of pantoprazole has been shown to suppress intragastric pH to a greater extent. We therefore aimed to determine the effect of pantoprazole at different time points of the day on thyroid function test (TFT) in levothyroxine-treated overt primary hypothyroidism.
METHODS
In this single centre, hospital based, prospective, two arm cross-over study (AB, BA), participants were randomized into 2 groups based on morning (6:00 am - 7:00 am simultaneously with the scheduled levothyroxine tablet) (group M) and evening (30 min before dinner) intake of 40 mg pantoprazole tablet (group N). After the initial 6 weeks (period 1), a washout period of 1 week for pantoprazole was given, and then both the groups crossed over for another 6 weeks (period 2). Patients were instructed to continue the same brand of levothyroxine tablet at empty stomach 1-hour before breakfast. Serum TSH was measured at baseline, week 6, and week 13.
RESULTS
Data from 30 patients, who completed the study with 100% compliance, were analysed. Mean TSH values of the study participants were significantly higher both at week 6 and week 13 compared to the baseline. Mean baseline serum TSH concentrations for groups M and N were 2.70 (± 1.36), and 2.20 (± 1.06) µlU/mL, respectively. Mean serum TSH concentrations at the end periods 1 and 2 for group M were 3.78 (± 4.29), and 3.76 (± 2.77) while the levels in group N were 3.30 (± 1.90), and 4.53 (± 4.590) µlU/mL, respectively. There was a significant rise in serum TSH concentration across periods 1 and 2 in both the groups (F = 3.87, p = 0.03). Within group changes in TSH across periods 1 and 2 were not statistically significant. Similarly difference in TSH between the groups, either at 6 weeks or at 13 weeks, were also not statistically significant.
CONCLUSIONS
Concomitant use of pantoprazole, even for 6 weeks, leads to significant elevation in serum TSH in levothyroxine-treated patients who are biochemically euthyroid, irrespective of timing of pantoprazole intake. Early morning and night-time administration of pantoprazole have similar effect on TFT in these patients.
PubMed: 37259094
DOI: 10.1186/s13044-023-00156-6