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International Journal of Chronic... 2024Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the... (Observational Study)
Observational Study
PURPOSE
Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the frequency of medication success among patients with COPD who initiated BGF using real-world data.
PATIENTS AND METHODS
Patients with a recorded diagnostic COPD code who started BGF with ≥2 prescriptions within 90-days were identified in the UK Optimum Patient Care Research Database and followed from first prescription until censoring at the end of follow-up (180-days), death, leaving database or end of data at 24/10/2022. The primary outcome was medication success at 90-days post-BGF initiation, defined as no major cardiac or respiratory event (ie no complicated COPD exacerbation, hospitalization for any respiratory event, myocardial infarction, new/hospitalized heart failure, and death) and no incidence of pneumonia. Medication success was also assessed at 180-days post-BGF initiation. Overall real-life medication success was claimed if the lower 95% confidence interval (CI) for the proportion of patients meeting the primary outcome was ≥70% (defined a priori).
RESULTS
Two hundred eighty-five patients were included. Prior to BGF initiation, these patients often had severe airflow obstruction (mean ppFEV: 54.5%), were highly symptomatic (mMRC ≥2: 77.9% (n = 205/263); mean CAT score: 21.7 (SD 7.8)), with evidence of short-acting β-agonist (SABA) over-use (≥3 inhalers/year: 62.1%, n=179/285), repeat OCS prescriptions (≥2 courses/year: 33.0%, n = 95/285) and multiple primary care consultations (≥2 visits/year: 61.1%, n = 174/285). Overall, 39.6% of patients (n = 113/285) switched from previous triple therapies. Real-life medication success was achieved by 96.5% of patients (n = 275/285 [95% CI: 93.6, 98.3]) during 90-days treatment with BGF and by 91.8% (n = 169/184 [95% CI: 86.9, 95.4]) of patients at 180-days. The prescribed daily dose of SABA remained stable over the study period.
CONCLUSION
The majority of patients initiating BGF experienced real-life medication success reflecting the absence of severe cardiopulmonary events. These benefits were apparent after 90-days of treatment and sustained over 180-days.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Female; Aged; Primary Health Care; Treatment Outcome; Bronchodilator Agents; Middle Aged; Time Factors; Adrenergic beta-2 Receptor Agonists; United Kingdom; Glycopyrrolate; Databases, Factual; Budesonide, Formoterol Fumarate Drug Combination; Lung; Muscarinic Antagonists; Drug Combinations; Retrospective Studies; Glucocorticoids; Aged, 80 and over
PubMed: 38813078
DOI: 10.2147/COPD.S452624 -
Journal of Integrative Neuroscience May 2024Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user's health but also poses risks and...
BACKGROUND
Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user's health but also poses risks and costs to society. Prolonged METH dependence has been shown to impair cognition, which may be the primary factor in impulsive drug-seeking behaviors and high relapse rates. However, the molecular mechanisms underlying METH addiction and METH-induced cognitive decline remain poorly understood.
METHODS
To illuminate the potential molecular mechanisms underpinning METH addiction, we compared serum protein expression levels between 12 long-term METH users and 12 healthy controls using label-free quantitative proteomics. Bioinformatic analyses were conducted to determine functional networks and protein-protein interactions.
RESULTS
In total, 23 differentially expressed proteins were identified between the two groups. The differentially expressed proteins were related to cognitive dysfunction, neuroinflammation, immune impairment, metabolic disturbances, and calcium binding and regulation.
CONCLUSIONS
These 23 proteins may underpin the multi-system damage induced by chronic METH exposure. Our findings provide novel insights into the molecular basis of METH addiction and inform potential prevention and treatment strategies for individuals with METH dependence.
Topics: Humans; Amphetamine-Related Disorders; Male; Methamphetamine; Cognitive Dysfunction; Adult; Proteomics; Central Nervous System Stimulants; Female; Young Adult
PubMed: 38812388
DOI: 10.31083/j.jin2305107 -
Drug Metabolism and Disposition: the... May 2024Heart failure (HF) is a chronic disease affecting 1-2% of the global population. I-labeled -iodobenzylguanidine (mIBG) is FDA-approved for cardiac imaging and prognosis...
Heart failure (HF) is a chronic disease affecting 1-2% of the global population. I-labeled -iodobenzylguanidine (mIBG) is FDA-approved for cardiac imaging and prognosis risk assessment in patients with HF. As a norepinephrine analog, mIBG is believed to be transported into adrenergic nerve terminals by the neuronal norepinephrine transporter (NET) and hence image sympathetic innervation of the myocardium. We previously showed that mIBG is an excellent substrate of organic cation transporter 3 (OCT3), an extraneuronal transporter expressed in cardiomyocytes. Here we evaluated the in vivo impact of Oct3 on mIBG disposition and tissue distribution using Oct3 knockout mice. and mice were administered with mIBG intravenously, and mIBG plasma pharmacokinetics and tissue exposures were determined. In mice, mIBG exhibited extensive accumulation in multiple tissues (heart, salivary gland, liver, adrenal gland). No difference was observed in overall plasma exposure between mice. Strikingly, cardiac mIBG was depleted in mice, resulting in 83% reduction in overall cardiac exposure (AUC: 12.7 versus 2.1 µghr/g). mIBG tissue exposure (AUC) was also reduced by 66%, 36%, and 31% in skeletal muscle, salivary gland, and lung respectively in mice. Our data demonstrated that Oct3 is the primary transporter responsible for cardiac mIBG uptake in vivo; and suggested that cardiac mIBG imaging mainly measures OCT3 activity in cardiomyocytes but not NET-mediated uptake in adrenergic nerve endings. Our findings challenge the current paradigm in interpreting cardiac mIBG imaging results and suggest OCT3 as a potential genetic risk marker for HF prognosis. I-mIBG is used for cardiac imaging and risk assessment in heart failure patients. Contrary to the current belief that mIBG tracks cardiac sympathetic innervation due to its uptake by the neuronal norepinephrine transporter, we have demonstrated that cardiac mIBG uptake is mediated by the extraneuronal transporter Oct3. Our findings warrant a re-evaluation of the scientific rationale behind cardiac mIBG imaging and further suggest OCT3 as a risk factor for disease progression in heart failure patients.
PubMed: 38811159
DOI: 10.1124/dmd.124.001709 -
Arquivos Brasileiros de Oftalmologia 2024
Topics: Humans; Timolol; Ophthalmic Solutions; Conjunctival Diseases; Cysts; Treatment Outcome; Male; Adult
PubMed: 38808909
DOI: 10.5935/0004-2749.2023-0313 -
BMC Pediatrics May 2024Lip infantile hemangiomas tend to show less volumetric regression and are more susceptible to visible sequelae in the involuted stage. Some of them still require...
BACKGROUND
Lip infantile hemangiomas tend to show less volumetric regression and are more susceptible to visible sequelae in the involuted stage. Some of them still require surgical management after propranolol therapy. This study aimed to evaluate the efficacy and safety of the Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach applied to lip reduction for those with involuted lip hemangiomas.
METHODS
A retrospective review was performed to evaluate patients with lip hemangioma who received previous propranolol treatment and underwent the aforementioned procedure. Demographic characteristics, lesion morphology, and medical history were reviewed. The Visual Analog Scale was applied to assess the postoperative appearance. Complications within 12 months postoperatively were recorded.
RESULTS
A total of 18 patients with lip hemangioma were eligible. All patients received oral propranolol therapy before surgery, with treatment duration ranging from 6.0 to 23.0 months. Their age at surgery ranged from 2.5 to 9.0 years. The median Visual Analog Scale scores were 8.0, ranging from 4.0 to 10.0. No severe complications were reported.
CONCLUSIONS
This modified technique based on the SMISS approach has proven reliable and effective in improving the aesthetic outcome for involuted lip infantile hemangiomas. Practical surgical techniques still play an important part in the propranolol era.
Topics: Humans; Retrospective Studies; Male; Female; Hemangioma; Lip Neoplasms; Propranolol; Child, Preschool; Child; Infant; Lip; Treatment Outcome; Lipoma
PubMed: 38807073
DOI: 10.1186/s12887-024-04838-4 -
BMC Anesthesiology May 2024Balanced propofol sedation is extensively used in endoscopic retrograde cholangiopancreatography (ERCP), but sedation-related adverse events (SRAEs) are common. In... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
A prospective, randomized, single-blinded study comparing the efficacy and safety of dexmedetomidine and propofol for sedation during endoscopic retrograde cholangiopancreatography.
BACKGROUND
Balanced propofol sedation is extensively used in endoscopic retrograde cholangiopancreatography (ERCP), but sedation-related adverse events (SRAEs) are common. In various clinical settings, the combination of dexmedetomidine with opioids and benzodiazepines has provided effective sedation with increased safety. The aim of this investigation was to compare the efficacy and safety of dexmedetomidine and propofol for sedation during ERCP.
METHODS
Forty-one patients were randomly divided into two groups: the dexmedetomidine (DEX) group and the propofol (PRO) group. Patients in the DEX group received an additional bolus of 0.6 μg kg dexmedetomidine followed by a dexmedetomidine infusion at 1.2 μg kg h, whereas the PRO group received 1-2 mg kg of propofol bolus followed by a propofol infusion at 2-3 mg kg h. During ERCP, the primary outcome was the incidence of hypoxemia (SpO < 90% for > 10 s). Other intraoperative adverse events were also recorded as secondary outcomes, including respiratory depression (respiratory rate of < 10 bpm min), hypotension (MAP < 65 mmHg), and bradycardia (HR < 45 beats min).
RESULTS
The incidence of hypoxemia was significantly reduced in the DEX group compared to the PRO group (0% versus 28.6%, respectively; P = 0.032). Patients in the PRO group exhibited respiratory depression more frequently than patients in the DEX group (35% versus 81%, respectively; P = 0.003). There were no significant differences in terms of hypotension and bradycardia episodes between groups. During the procedures, the satisfaction scores of endoscopists and patients, as well as the pain and procedure memory scores of patients were comparable between groups.
CONCLUSION
In comparison with propofol, dexmedetomidine provided adequate sedation safety with no adverse effects on sedation efficacy during ERCP.
TRIAL REGISTRATION
Chinese Clinical Trial Registry, ChiCTR2200061468, 25/06/2022.
Topics: Humans; Dexmedetomidine; Cholangiopancreatography, Endoscopic Retrograde; Propofol; Male; Female; Hypnotics and Sedatives; Middle Aged; Prospective Studies; Single-Blind Method; Aged; Adult; Hypoxia; Conscious Sedation
PubMed: 38807059
DOI: 10.1186/s12871-024-02572-z -
Journal of Insect Science (Online) May 2024The parasitic mite Varroa destructor (Anderson and Trueman) is one of the greatest stressors of Apis mellifera (L.) honey bee colonies. When Varroa infestations reach...
The parasitic mite Varroa destructor (Anderson and Trueman) is one of the greatest stressors of Apis mellifera (L.) honey bee colonies. When Varroa infestations reach damaging levels during fall, rapid control is necessary to minimize damage to colonies. We performed a field trial in the US Southeast to determine if a combination of registered treatments (Apivar, amitraz-based; and Apiguard, thymol-based) could provide rapid and effective control of Varroa. We compared colonies that received this combination treatment against colonies that received amitraz-based positive control treatments: (i) Apivar alone; or (ii) amitraz emulsifiable concentrate ("amitraz EC"). While not registered, amitraz EC is used by beekeepers in the United States in part because it is thought to control Varroa more rapidly and effectively than registered products. Based on measurements of Varroa infestation rates of colonies after 21 days of treatment, we found that the combination treatment controlled Varroa nearly as rapidly as the amitraz EC treatment: this or other combinations could be useful for Varroa management. At the end of the 42-day trial, colonies in the amitraz EC group had higher bee populations than those in the Apivar group, which suggests that rapid control helps reduce Varroa damage. Colonies in the combination group had lower bee populations than those in the amitraz EC group, which indicates that the combination treatment needs to be optimized to avoid damage to colonies.
Topics: Animals; Toluidines; Bees; Varroidae; Thymol; Acaricides; Beekeeping
PubMed: 38805647
DOI: 10.1093/jisesa/ieae022 -
Circulation May 2024
Letter by Cardinale et al Regarding Article, "Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial".
Topics: Humans; Troponin I; Cardiotoxicity; Anthracyclines; Adrenergic beta-Antagonists; Randomized Controlled Trials as Topic; Angiotensin Receptor Antagonists; Prospective Studies; Multicenter Studies as Topic; Drug Therapy, Combination
PubMed: 38805580
DOI: 10.1161/CIRCULATIONAHA.123.068069 -
Circulation May 2024
Response by Henriksen et al Regarding Article, "Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial".
Topics: Humans; Troponin I; Cardiotoxicity; Anthracyclines; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Randomized Controlled Trials as Topic; Prospective Studies; Multicenter Studies as Topic; Drug Therapy, Combination
PubMed: 38805577
DOI: 10.1161/CIRCULATIONAHA.124.069375 -
Proceedings of the National Academy of... Jun 2024Many animals exhibit remarkable colors that are produced by the constructive interference of light reflected from arrays of intracellular guanine crystals. These animals...
Many animals exhibit remarkable colors that are produced by the constructive interference of light reflected from arrays of intracellular guanine crystals. These animals can fine-tune their crystal-based structural colors to communicate with each other, regulate body temperature, and create camouflage. While it is known that these changes in color are caused by changes in the angle of the crystal arrays relative to incident light, the cellular machinery that drives color change is not understood. Here, using a combination of 3D focused ion beam scanning electron microscopy (FIB-SEM), micro-focused X-ray diffraction, superresolution fluorescence light microscopy, and pharmacological perturbations, we characterized the dynamics and 3D cellular reorganization of crystal arrays within zebrafish iridophores during norepinephrine (NE)-induced color change. We found that color change results from a coordinated 20° tilting of the intracellular crystals, which alters both crystal packing and the angle at which impinging light hits the crystals. Importantly, addition of the dynein inhibitor dynapyrazole-a completely blocked this NE-induced red shift by hindering crystal dynamics upon NE addition. FIB-SEM and microtubule organizing center (MTOC) mapping showed that microtubules arise from two MTOCs located near the poles of the iridophore and run parallel to, and in between, individual crystals. This suggests that dynein drives crystal angle change in response to NE by binding to the limiting membrane surrounding individual crystals and walking toward microtubule minus ends. Finally, we found that intracellular cAMP regulates the color change process. Together, our results provide mechanistic insight into the cellular machinery that drives structural color change.
Topics: Animals; Zebrafish; Norepinephrine; Color; Pigmentation; Microscopy, Electron, Scanning; Zebrafish Proteins
PubMed: 38805288
DOI: 10.1073/pnas.2308531121