scholarly journals Dosing Therapeutic Radiopharmaceuticals in Obese Patients

2022 ◽  
Vol 23 (2) ◽  
pp. 818
Author(s):  
Merel van Nuland ◽  
Tessa F. Ververs ◽  
Marnix G. E. H. Lam
Keyword(s):  
Relevant Literature ◽  
Maximum Tolerated Dose ◽  
Obese Patients ◽  
Physiological Processes ◽  
Radium 223 ◽  
Pharmacokinetic Properties ◽  
Practical Guidelines ◽  
Prevalence Of Obesity ◽  
Dose Recommendations ◽  
Drug Pharmacokinetics

The prevalence of obesity has increased dramatically in the Western population. Obesity is known to influence not only the proportion of adipose tissue but also physiological processes that could alter drug pharmacokinetics. Yet, there are no specific dosing recommendations for radiopharmaceuticals in this patient population. This could potentially lead to underdosing and thus suboptimal treatment in obese patients, while it could also lead to drug toxicity due to high levels of radioactivity. In this review, relevant literature is summarized on radiopharmaceutical dosing and pharmacokinetic properties, and we aimed to translate these data into practical guidelines for dosing of radiopharmaceuticals in obese patients. For radium-223, dosing in obese patients is well established. Furthermore, for samarium-153-ethylenediaminetetramethylene (EDTMP), dose-escalation studies show that the maximum tolerated dose will probably not be reached in obese patients when dosing on MBq/kg. On the other hand, there is insufficient evidence to support dose recommendations in obese patients for rhenium-168-hydroxyethylidene diphosphonate (HEDP), sodium iodide-131, iodide 131-metaiodobenzylguanidine (MIBG), lutetium-177-dotatate, and lutetium-177-prostate-specific membrane antigen (PSMA). From a pharmacokinetic perspective, fixed dosing may be appropriate for these drugs. More research into obese patient populations is needed, especially in the light of increasing prevalence of obesity worldwide.

Obesity and inflammation: colorectal cancer engines

2021 ◽  
Vol 14 ◽  
Author(s):  
Lara J. Bou Malhab ◽  
Wael M. Abdel-Rahman
Keyword(s):  
Colorectal Cancer ◽  
Immune Cell ◽  
Obese Patients ◽  
Epigenetic Alterations ◽  
Molecular Alterations ◽  
Stat3 Signaling ◽  
Therapeutic Choice ◽  
Prevalence Of Obesity ◽  
Inhibitory Molecules

: The prevalence of obesity continues to increase to the extent that it became a worldwide pandemic. An accumulating body of evidence has associated obesity with the development of different types of cancer, including colorectal cancer, which is a notorious disease with a high mortality rate. At the molecular level, colorectal cancer is a heterogenous disease characterized by a myriad of genetic and epigenetic alterations associated with various forms of genomic instability (detailed in Supplementary Materials). Recently, the microenvironment has emerged as a major factor in carcinogenesis. Our aim is to define the different molecular alterations leading to the development of colorectal cancer in obese patients with a focus on the role of the microenvironment in carcinogenesis. We also highlight all existent molecules in clinical trials that target the activated pathways in obesity-associated colorectal cancer, whether used as single treatments or in combination. Obesity predisposes to colorectal cancer via creating a state of chronic inflammation with dysregulated adipokines, inflammatory mediators, and other factors such as immune cell infiltration. A unifying theme in obesity-mediated colorectal cancer is the activation of the PI3K/AKT, mTOR/MAPK, and STAT3 signaling pathways. Different inhibitory molecules towards these pathways exist, increasing the therapeutic choice of obesity-associated colon cancer. However, obese patients are more likely to suffer from chemotherapy overdosing. Preventing obesity through maintaining a healthy and active lifestyle remains to be the best remedy.

Function-specific Design Principles for the Electronic Health Record

2016 ◽  
Vol 60 (1) ◽  
pp. 578-582 ◽  
Author(s):  
Jason J. Saleem ◽  
Jennifer Herout ◽  
Nancy R. Wilck
Keyword(s):  
Electronic Health Record ◽  
Relevant Literature ◽  
Clinical Decision ◽  
Design Principles ◽  
Health Record ◽  
Progress Notes ◽  
Practical Guidelines ◽  
Electronic Health ◽  
Future Work ◽  
Clinical Reminders

This practice-oriented paper provides a collection of design principles that are specific to certain functions within the electronic health record (EHR). Design principles for EHRs tend to be broad rules of thumb rather than specific and actionable because the relevant literature is organized by specific EHR functions. That is, a good amount of research has been conducted on specific functions, rather than EHRs as a whole. Based on the relevant literature, we provide design principles with underlying rationale for progress notes, problem list, consults, clinical reminders, clinical decision support, medication list, medication alerts, and medication reconciliation. This paper is meant to offer a collection of practical guidelines for designers, grounded in the academic literature, that are more actionable than broad usability heuristics. Future work should include refinement of these principles through systematic literature review and the inclusion of additional EHR functions.

scholarly journals Application of BAROS’ questionnaire in obese patients undergoing bariatric surgery with 2 years of evolution

2017 ◽  
Vol 54 (1) ◽  
pp. 60-64 ◽  
Author(s):  
Caetano de QUEIROZ ◽  
José Afonso SALLET ◽  
Pedro Gabriel Melo DE BARROS E SILVA ◽  
Luzia da Gloria Pereira de Sousa QUEIROZ ◽  
Jélis Arenas PIMENTEL ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Weight Loss ◽  
Long Term Results ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Index Reduction ◽  
Clinical Complications ◽  
Number Of Patients ◽  
Prevalence Of Obesity

ABSTRACT BACKGROUND -In recent decades, the high prevalence of obesity in the general population has brought serious concerns in terms of public health. Contrarily to conventional treatment involving dieting and physical exercising, often ineffective in generating long term results, bariatric operations have been an effective method for sustained weight loss in morbidly obese individuals. The Bariatric Analysis and Reporting Outcome System (BAROS) is an objective and recognized system in the overall evaluation of results after bariatric surgery. OBJECTIVE To investigate results concerning a casuistic of morbidly obese patients undergoing bariatric surgery over a 2-year follow-up in terms of weight loss, related medical conditions, safety and changes in quality of life. METHODS A total of 120 obese (17 male and 103 female) patients, who underwent bariatric surgery, were assessed and investigated using the BAROS system after a 2- year follow-up. RESULTS Patients obtained a mean excess weight loss of 74.6 (±15.9) % and mean body mass index reduction of 15.6 (±4.4) Kg/m2. Pre-surgical comorbidities were present in 71 (59%) subjects and they were totally (86%) or partially (14%) resolved. Complications resulting specifically from the surgical procedure were observed in 4.2% of cases (two bowel obstructions requiring re-operation, and three stomal stenosis treated with endoscopic dilation). Sixteen subjects (13% of total number of patients) presented minor clinical complications managed through outpatient care. The final scores for the BAROS questionnaire showcased excellent to good results in 99% of cases (excellent 44%, very good 38%, good 23%, acceptable 1%). CONCLUSION According to the BAROS questionnaire, bariatric surgery is a safe and effective method for managing obesity and associated clinical comorbidities, allowing for satisfactory results after a 2-year follow-up. Future studies should address other clinical and psychosocial variables that impact outcome as well as allow for longer follow-ups.

Staged ultrasound-guided liposuction for hidden arteriovenous fistulas in obese patients

VASA ◽  
2018 ◽  
Vol 47 (5) ◽  
pp. 403-407
Author(s):  
Gabor Cs.Nagy ◽  
Reiner Verwiebe ◽  
Matthias Wunsch
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Relevant Literature ◽  
Skin Surface ◽  
Obese Patients ◽  
Ultrasound Guided ◽  
Arteriovenous Fistulas ◽  
The Mean ◽  
Stage Renal Disease ◽  
Subcutaneous Adipose

Abstract. Background: In obese patients with end stage renal disease, puncturing matured arteriovenous fistulas (AVF) that run deep under the skin surface may prove difficult. To achieve reliable puncturability, there are several surgical solutions. Superficialization with mobilization is common. With some newer options (lipectomy and liposuction) subcutaneous adipose tissue is surgically reduced. There are only a few authors who have published their experience with liposuction and we want to add our own results. Patients and methods: We report our experience with ultrasound-guided liposuction (USGL). We introduce liposuction cannulas via small incisions to reduce the subcutaneous adipose tissue overlying the planned cannulation zones under ultrasound control using tumescent anaesthesia till the prospective needle access segments become easily palpable. So far, we have used this technique for cephalic forearm and upper arm fistulas only. Furthermore, we review the relevant literature. Results: From February 2014 through November 2016, six patients were treated using USGL. Their body mass indices ranged from 30.8 to 53.8 kg/m2 (mean 37.6). The mean depths of the AVFs beneath the skin surface were 13.3 (8–20) mm before and 5.1 (3.5–6) mm after surgery. The mean time of the procedure was 15 minutes. There were no postoperative complications. In five patients, the AVFs could reliably be punctured after three weeks. One patient is not yet on dialysis. During the follow-up period of 24 (11–43) months, all six AVFs remained primarily patent. In the literature, we found nine reports on altogether 81 patients undergoing USGL. Almost all noteworthy complications occurred only after ultrasound-powered liquefaction of adipose tissue, which was only used by a single investigator. Conclusions: USGL is a method that can be learned easily, is minimally invasive, seems to be safe, and requires only short operation times.

First-in-human phase I study of ARV-110, an androgen receptor (AR) PROTAC degrader in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) following enzalutamide (ENZ) and/or abiraterone (ABI).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3500-3500 ◽  
Author(s):  
Daniel Peter Petrylak ◽  
Xin Gao ◽  
Nicholas J. Vogelzang ◽  
Mary Harlow Garfield ◽  
Ian Taylor ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasma Concentrations ◽  
Ubiquitin Proteasome System ◽  
Maximum Tolerated Dose ◽  
Prior Therapy ◽  
Radium 223 ◽  
Psa Response ◽  
Orally Bioavailable ◽  
Castrate Resistant ◽  
Anti Tumor Activity

3500 Background: Proteolysis Targeting Chimera (PROTAC) protein degraders induce selective degradation of targeted proteins by engaging the ubiquitin proteasome system. ARV-110 is an orally bioavailable PROTAC that specifically degrades AR ≥ 95% and achieves anti-tumor activity in ENZ-naïve and -resistant prostate cancer xenograft models. Methods: To define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ARV-110, pts with ≥ 2 prior therapies for mCRPC, including ENZ and/or ABI, received ARV-110 orally once daily. Dose escalation is per 3+3 design. Endpoints include dose limiting toxicities (DLTs), adverse events (AEs), pharmacokinetics (PK), biomarkers (e.g., AR mutation analysis), RECIST and PSA response. Results: By January 2020, 18 pts were dosed: 35 mg (N = 3), 70 mg (N = 4), 140 mg (N = 8), 280 mg (N = 3). 12 pts received both ENZ and ABI; 14 received prior chemotherapy. 1 of 18 pts experienced a DLT (280 mg) of Grade (Gr) 4 elevated AST/ALT followed by acute renal failure while taking rosuvastatin (ROS). A 2nd pt had Gr 3 AST/ALT with ROS that resolved off ROS, permitting ARV-110 retreatment. ROS plasma concentrations demonstrated significant increases concurrent with AST/ALT elevations in both pts. Subsequently, ROS was prohibited without further ≥Gr 2 AST/ALT AEs. No other related Gr 3/4 AEs were reported. ARV-110 PK was generally dose proportional and at 140 mg reached levels associated with preclinical anti-tumor activity. 15 pts were evaluable for PSA response (excludes 1 pt stopped after 1 dose for early progression and 2 pts initiated 2 weeks before cutoff, all at 140 mg). Of these, 8 pts initiated dosing at ≥140 mg. 2 pts achieved confirmed PSA declines of >50%, both at 140 mg. Prior therapy in both pts included ENZ and ABI, chemotherapy, bicalutamide and radium-223 plus other regimens. 1 pt had 2 AR mutations known to confer ENZ resistance. The 2nd pt also achieved an unconfirmed RECIST partial response (confirmatory scan pending). Both responses were ongoing at data cutoff (8+ and 21+ weeks of treatment). Conclusions: To date, ARV-110 has an acceptable safety profile. Concurrent ROS is now prohibited. MTD has not yet been established; determination of RP2D continues. ARV-110 demonstrates antitumor activity in mCRPC after ENZ/ABI with 2 ongoing confirmed PSA responses, one of which was associated with tumor reduction. Updated data for this first PROTAC in clinical testing will be presented. Clinical trial information: NCT03888612 .

scholarly journals Drug-Induced Liver Injury Associated with the Use of Everolimus in a Liver Transplant Patient

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Serena Patel ◽  
Michel H. Mendler ◽  
Mark A. Valasek ◽  
Shirley M. Tsunoda
Keyword(s):  
Liver Injury ◽  
Liver Transplant ◽  
Transplant Patient ◽  
Liver Transplant Recipient ◽  
Relevant Literature ◽  
Drug Discontinuation ◽  
Upward Trend ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Pharmacokinetic Properties

Drug-induced liver injury (DILI) has not been previously reported as a complication of treatment with everolimus. A 56-year-old Caucasian male liver transplant recipient developed DILI after receiving everolimus. Elevations in transaminase levels occurred within a week of starting everolimus and an upward trend in the transaminase levels continued with supporting histopathologic changes confirmed by liver biopsy. Within one week of drug discontinuation, his liver enzymes normalized to baseline. This report includes a brief review of the pharmacokinetic properties of everolimus, a review of the relevant literature, and an analysis using the RUCAM and Naranjo algorithms.

scholarly journals Anthropometric measurement - An easy approach for evaluation of obesity

2014 ◽  
Vol 42 (1) ◽  
pp. 25-27
Author(s):  
MT Islam ◽  
M Rokonozaman
Keyword(s):  
Blood Pressure ◽  
Anthropometric Measurements ◽  
Anthropometric Measurement ◽  
Obese Patients ◽  
Control Groups ◽  
Exclusion Criteria ◽  
Medical College ◽  
Prevalence Of Obesity ◽  
And Control ◽  
Selection Of

Now a day’s obesity is a burden worldwide. The prevalence of obesity is increasing in both the developed and developing countries. To investigate the anthropometric measurement in obesity. This cross study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh. Inclusion and exclusion criteria are strictly maintained for selection of study and control groups. Anthropometric measurements were performed in 150 cases of overweight and obese. BMI, WC, WHR, blood pressure were high in obese group. Obesity affects various anthropometric measurements and may be used to routinely evaluate obese patients. DOI: http://dx.doi.org/10.3329/bmj.v42i1.18976 Bangladesh Med J. 2013 Jan; 42 (1): 25-27

P52 LIVER REDUCTION DIET IN PATIENTS UNDERGOING GASTRO-OESOPHAGECTOMIES

2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
Veeralakshmanan Pushpa ◽  
Wadhawan Himanshu ◽  
Sanders Grant ◽  
M Humphreys Lee ◽  
Berrisford Richard ◽  
...  
Keyword(s):  
Hybrid Approach ◽  
Gastric Surgery ◽  
Oesophageal Adenocarcinoma ◽  
Obese Patients ◽  
Operative Death ◽  
Chyle Leak ◽  
Thoracoscopic Approach ◽  
Increased Risk ◽  
Prevalence Of Obesity ◽  
Fatty Livers

Abstract Aim The prevalence of obesity has nearly doubled in the last 10 years and is a known risk factor for oesophageal adenocarcinoma [1]. There is an increasing popularity with minimally invasive esophagectomies employing laparoscopic and/or thoracoscopic approach [2]. Obesity can complicate technical aspects of surgery. There is increased risk of retraction trauma from fatty livers and the operative field of the gastro-oesophageal area is limited in obese patients. Pre-operative liver reduction diet (LRD) is a common practice in patients undergoing bariatric surgery. We propose a pre-operative LRD for obese patients undergoing oesophago-gastric surgery for cancer to be safe and can help with the overall complexity of the surgery. Background & Methods In our regional tertiary unit, we adopted a 2-week pre-operative LRD for patients undergoing oesophago-gastric surgery with BMI >30 Kg m-2. Data was collected prospectively from January 2017 to January 2019 for all patients undergoing oesophago-gastric surgery. Results 142 patients underwent oesophago-gastric surgery in the study period, 31 with a BMI >30 Kg m-2. 20 of the 31 (64.5%) received and completed LRD prior to their operation. For 9 patients, no reason was documented for incompletion of diet and 2 were unable to manage the diet. For 75% (15/20) of these patients, surgery was randomized and completed using the hybrid approach (laparoscopic abdomen and open chest) and the rest undergoing open procedure, as per the ROMIO trial [3]. Although a small number of cases for comparison, there were no significant differences observed in length of stay (LOS), complications including pneumonia, chyle leak and anastomotic leak in our patient group receiving LRD compared to high BMI patients in the literature without LRD. Conclusion Oesophago-gastric surgeons in our unit find pre-operative LRD in obese patients leads to improved flexibility of the liver for easier retraction and a better exposure of the operating field, especially around the hiatus. Implementation of pre-operative LRD in obese patients undergoing oesophago-gastric cancer surgery has been shown to be safe. We aim to continue to record post-operative complications, peri-operative death and LOS and expand the sample size for our study.

scholarly journals Recommendations for the treatment of epilepsy in adult and pediatric patients in Belgium: 2020 update

2020 ◽  
Author(s):  
Paul Boon ◽  
Susana Ferrao Santos ◽  
Anna C. Jansen ◽  
Lieven Lagae ◽  
Benjamin Legros ◽  
...  
Keyword(s):  
Health Care Professionals ◽  
Generic Substitution ◽  
Pediatric Patients ◽  
Relevant Literature ◽  
New Drugs ◽  
Drug Resistant ◽  
Early Referral ◽  
Pharmacokinetic Properties ◽  
Adults And Children ◽  
Drug Resistant Epilepsy

Abstract To guide health care professionals in Belgium in selecting the appropriate antiepileptic drugs (AEDs) for their epilepsy patients, a group of Belgian epilepsy experts developed recommendations for AED treatment in adults and children (initial recommendations in 2008, updated in 2012). As new drugs have become available, others have been withdrawn, new indications have been approved and recommendations for pregnant women have changed, a new update was pertinent. A group of Belgian epilepsy experts (partly overlapping with the group in charge of the 2008/2012 recommendations) evaluated the most recent international guidelines and relevant literature for their applicability to the Belgian situation (registration status, reimbursement, clinical practice) and updated the recommendations for initial monotherapy in adults and children and add-on treatment in adults. Recommendations for add-on treatment in children were also included (not covered in the 2008/2012 publications). Like the 2008/2012 publications, the current update also covers other important aspects related to the management of epilepsy, including the importance of early referral in drug-resistant epilepsy, pharmacokinetic properties and tolerability of AEDs, comorbidities, specific considerations in elderly and pregnant patients, generic substitution and the rapidly evolving field of precision medicine.

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