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Journal of the American Academy of... Aug 2019Radiation dermatitis is a common sequela of radiation therapy; up to 95% of patients will develop moderate-to-severe skin reactions. No criterion standard currently... (Review)
Review
Radiation dermatitis is a common sequela of radiation therapy; up to 95% of patients will develop moderate-to-severe skin reactions. No criterion standard currently exists for the treatment of acute radiation-induced skin toxicity. It is therefore imperative to develop a greater understanding of management options available to allow clinicians to make informed decisions when managing radiation oncology patients. This literature review discusses the topical agents that have been studied for the treatment of acute radiation dermatitis, reviews their mechanisms of action, and presents a treatment algorithm for clinicians managing patients experiencing radiation dermatitis.
Topics: Acute Disease; Adrenal Cortex Hormones; Algorithms; Anti-Infective Agents, Local; Bandages; Biological Products; Dermatologic Agents; Ethanolamines; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Plant Preparations; Radiodermatitis; Radiotherapy; Silver Sulfadiazine; Sucralfate; Vitamins
PubMed: 30802561
DOI: 10.1016/j.jaad.2019.02.047 -
BMJ (Clinical Research Ed.) Jan 2020To determine, in critically ill patients, the relative impact of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, or no... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine, in critically ill patients, the relative impact of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, or no gastrointestinal bleeding prophylaxis (or stress ulcer prophylaxis) on outcomes important to patients.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature up to March 2019.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS
We included randomised controlled trials that compared gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. A parallel guideline committee ( Rapid Recommendation) provided critical oversight of the systematic review, including identifying outcomes important to patients. We performed random-effects pairwise and network meta-analyses and used GRADE to assess certainty of evidence for each outcome. When results differed between low risk and high risk of bias studies, we used the former as best estimates.
RESULTS
Seventy two trials including 12 660 patients proved eligible. For patients at highest risk (>8%) or high risk (4-8%) of bleeding, both PPIs and H2RAs probably reduce clinically important gastrointestinal bleeding compared with placebo or no prophylaxis (odds ratio for PPIs 0.61 (95% confidence interval 0.42 to 0.89), 3.3% fewer for highest risk and 2.3% fewer for high risk patients, moderate certainty; odds ratio for H2RAs 0.46 (0.27 to 0.79), 4.6% fewer for highest risk and 3.1% fewer for high risk patients, moderate certainty). Both may increase the risk of pneumonia compared with no prophylaxis (odds ratio for PPIs 1.39 (0.98 to 2.10), 5.0% more, low certainty; odds ratio for H2RAs 1.26 (0.89 to 1.85), 3.4% more, low certainty). It is likely that neither affect mortality (PPIs 1.06 (0.90 to 1.28), 1.3% more, moderate certainty; H2RAs 0.96 (0.79 to 1.19), 0.9% fewer, moderate certainty). Otherwise, results provided no support for any affect on mortality, infection, length of intensive care stay, length of hospital stay, or duration of mechanical ventilation (varying certainty of evidence).
CONCLUSIONS
For higher risk critically ill patients, PPIs and H2RAs likely result in important reductions in gastrointestinal bleeding compared with no prophylaxis; for patients at low risk, the reduction in bleeding may be unimportant. Both PPIs and H2RAs may result in important increases in pneumonia. Variable quality evidence suggested no important effects of interventions on mortality or other in-hospital morbidity outcomes.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019126656.
Topics: Critical Illness; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Patient Selection; Proton Pump Inhibitors; Risk Adjustment
PubMed: 31907166
DOI: 10.1136/bmj.l6744 -
Journal of Pediatric Gastroenterology... Jul 2021Button batteries (BB) remain a health hazard to children as ingestion might lead to life-threatening complications, especially if the battery is impacted in the...
Diagnosis, Management, and Prevention of Button Battery Ingestion in Childhood: A European Society for Paediatric Gastroenterology Hepatology and Nutrition Position Paper.
Button batteries (BB) remain a health hazard to children as ingestion might lead to life-threatening complications, especially if the battery is impacted in the esophagus. Worldwide initiatives have been set up in order to prevent and also timely diagnose and manage BB ingestions. A European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) task force for BB ingestions has been founded, which aimed to contribute to reducing the health risks related to this event. It is important to focus on the European setting, next to other worldwide initiatives, to develop and implement effective management strategies. As one of the first initiatives of the ESPGHAN task force, this ESPGHAN position paper has been written. The literature is summarized, and prevention strategies are discussed focusing on some controversial topics. An algorithm for the diagnosis and management of BB ingestions is presented and compared to previous guidelines (NASPGHAN, National Poison Center). In agreement with earlier guidelines, immediate localization of the BB is important and in case of esophageal impaction, the BB should be removed instantly (preferably <2 hours). Honey and sucralfate can be considered in ingestions ≤12 hours while waiting for endoscopic removal but should not delay it. In case of delayed diagnosis (first confirmation of the BB on X-ray >12 hours after ingestion or time point of removal >12 hours after ingestion) and esophageal impaction the guideline suggests to perform a CT scan in order to evaluate for vascular injury before removing the battery. In delayed diagnosis, even if the battery has passed the esophagus, endoscopy to screen for esophageal damage and a CT scan to rule out vascular injury should be considered even in asymptomatic children. In asymptomatic patients with early diagnosis (≤12 hours after ingestion) and position of the BB beyond the esophagus, one can monitor with repeat X-ray (if not already evacuated in stool) in 7 to 14 days, which is different from previous guidelines where repeat X-ray and removal is recommended after 2-4 days and is also based on age. Finally, prevention strategies are discussed in this paper.
Topics: Child; Eating; Electric Power Supplies; Esophagus; Foreign Bodies; Gastroenterology; Humans
PubMed: 33555169
DOI: 10.1097/MPG.0000000000003048 -
Frontiers in Endocrinology 2020Administration of the optimal dose of levothyroxine (LT4) is crucial to restore euthyroidism after total thyroidectomy. An insufficient or excessive dosage may result in... (Review)
Review
Administration of the optimal dose of levothyroxine (LT4) is crucial to restore euthyroidism after total thyroidectomy. An insufficient or excessive dosage may result in hypothyroidism or thyrotoxicosis, either one associated with a number of symptoms/complications. Most literature regarding the LT4 dosage deals with the treatment of primary hypothyroidism, whereas a limited number of studies handle the issue of thyroxin replacement after total thyroidectomy. A literature review was performed focusing on all papers dealing with this topic within the last 15 years. Papers that reported a scheme to calculate the proper LT4 dose were collected and compared to set up a review exploring limits and drawbacks of LT4 replacement therapy in the wide population of patients who had undergone thyroidectomy. Most of the methods for monitoring and adjusting thyroid hormone replacement after thyroidectomy for benign disease use LT4 at an empirical dose of approximately 1.6 μg/kg, with subsequent changes according to thyroid function test results and assessments of the patient's symptoms. Approximately 75% of patients require a dose adjustment, suggesting that factors other than body weight play a role in the determination of the proper LT4 dose. Hence, several schemes are reported in the literature for the proper initial dose of LT4. An inadequate level of thyroid hormone levels in these patients can be due to several factors. The most common ones that lead to the necessity of LT4 dose adjustments include lack of compliance, changes in LT4 formulation, dosage errors, increased serum levels of T4-binding globulin, body mass changes, and dietary habits. Moreover, concomitant ingestion of calcium supplements, ferrous sulfate, proton-pump inhibitors, bile acid sequestrants, and sucralfate might influence LT4 absorption and/or metabolism. Furthermore, some gastrointestinal conditions and their treatments can contribute to suboptimal LT4 performance by altering gastric acidity and thereby reducing its bioavailability, particularly in the solid form. Beyond the classic tablet form, new formulations of LT4, such as a soft gel capsule and an oral solution, recently became available. The liquid formulation is supposed to overcome the food and beverages interference with absorption of LT4 tablets.
Topics: Animals; Biomarkers; Dose-Response Relationship, Drug; Humans; Hypothyroidism; Thyroid Function Tests; Thyroid Neoplasms; Thyroidectomy; Thyroxine
PubMed: 33584551
DOI: 10.3389/fendo.2020.626268 -
Laryngoscope Investigative... Jun 2021Button batteries (BB) are found in common household items and can lead to significant morbidity and mortality in the pediatric population when ingested. BBs are made of... (Review)
Review
UNLABELLED
Button batteries (BB) are found in common household items and can lead to significant morbidity and mortality in the pediatric population when ingested. BBs are made of various chemistries and have a unique size and shape that yield significant injury when lodged in the pediatric esophagus. BBs create a local tissue pH environment of 10 to 13 and can induce liquefactive necrosis at the negative pole. This initial injury can progress with further tissue breakdown even after removal. Unfortunately, patients may present with vague symptoms similar to viral illnesses and there is not always a known history of ingestion. Plain film X-ray can be diagnostic. Exposure can lead to caustic injury within 2 hours. Thus, timely endoscopic removal is the mainstay of treatment. Novel mitigation and neutralization strategies have been implemented into treatment guidelines. These include the preremoval ingestion of honey or sucralfate and intraoperative irrigation with acetic acid. Depending on the severity of injury following removal, careful consideration should be given for potential delayed complications including fistulization into major vessels which often leads to death. The National Button Battery Taskforce and several industry members have implemented prevention strategies such as educational safety outreach campaigns, child-resistant packaging changes, and warning labels. Governmental regulation and industry changes are key to limit not only the amount of BB ingestions, but also the devastating consequences that can result. Anonymous reporting of BB injuries through the Global Injury Research Collaborative has been made convenient and centralized through the advent of a user-friendly smartphone iOS/App Store and Android/GooglePlay application called the "GIRC App"; all specialists who manage foreign body cases should contribute their cases to help prevent future injuries. BB ingestion must be recognized and treated promptly using a multidisciplinary approach to optimize outcomes for these patients. Ultimately, a safer BB technology is critically needed to reduce or eliminate the severe and life-threatening injuries in children.
LEVEL OF EVIDENCE
5.
PubMed: 34195377
DOI: 10.1002/lio2.535 -
Journal of Family Medicine and Primary... Jul 2019The occurrence of chronic proctitis as a side effect among radiotherapy patients is about 5%. Radiation proctitis and consequent development of chronic proctitis are not... (Review)
Review
The occurrence of chronic proctitis as a side effect among radiotherapy patients is about 5%. Radiation proctitis and consequent development of chronic proctitis are not associated to each other. However, a lot of samples of proctitis that are limited easily could be treated by typical remedial techniques. Improvements in radiotherapy techniques that make possible the delivery of superior doses of radiation could easily reduce both chronic and acute proctitis. The step-by-step remedial procedure for treatment of this disorder starts with conservative remedial management and includes iron substitution as a second-line therapy. For patients who did not receive initial therapies, sucralfate injection, topical corticosteroids, and antidiarrhea therapy were provided as a means of aggressive care. In cases of continuous rectal bleeding, remedial laser techniques and formaldehyde administration should be attempted before surgical therapy. When surgical therapy is required, a descending or transverse colostomy must be carried out. Advanced methods such as intraperitoneal injections of formalin or novel methods of cold therapy and radiofrequency ablation (RFA) provide a wider remedial field. Exceptionally, unanticipated conclusion of neosquamous wound healing via RFA may have additional preponderances in stopping symptoms and may require better assessment through accurate randomized examination. Since aggressive treatments like coloanal anastomosis and colorectal surgery are correlated with remarkable mortality and morbidity, they must be considered as the final course of remedial treatment.
PubMed: 31463226
DOI: 10.4103/jfmpc.jfmpc_333_19 -
Journal of Gastroenterology and... Dec 2014Although Andre Robert's historic article on "gastric cytoprotection" in 1979 introduced this new name and concept, gastroprotective drugs (e.g. sofalcone, sucralfate),... (Review)
Review
Although Andre Robert's historic article on "gastric cytoprotection" in 1979 introduced this new name and concept, gastroprotective drugs (e.g. sofalcone, sucralfate), which prevent and/or accelerate healing of gastric ulcers without inhibiting acid secretion, were known in Japan before or around that time. But since Robert's studies were solely focused on prostaglandins (PG), they became the center of gastrointestinal research for more than 30 years. As endogenous products, PG were implicated in mediating the gastroprotective effect of other drugs such as sofalcone and sucralfate, despite that the cyclooxygenase inhibitor indomethacin diminished but never abolished gastroprotection by other drugs. Another group of endogenous substances, that is, sulfhydryls (SH), investigated in parallel with PG, also seem to play a mechanistic role in gastroprotection, especially since SH alkylators like N-ethylmaleimide counteract virtually any form of gastroprotection. In Robert's terms of "prevention of chemically induced acute mucosal lesions," so far no single mechanism could explain the beneficial effects of diverse protective agents, but I argue that these two endogenous substances (i.e. PG, SH), in addition to histamine, are the main mechanistic mediators of acute gastroprotection: PG and histamine, because as mediators of acute inflammation, they increase vascular permeability (VP), and SH scavenge free radicals. This is contrary to the search for a single mechanism of action, long focused on enhanced secretion of mucus and/or bicarbonate that may contribute but cannot explain all forms of gastroprotection. Nevertheless, based on research work of the last 30 years, in part from our lab, a new mechanistic explanation of gastroprotection may be formulated: it's a complex but orderly and evolution-based physiologic response of the gastric mucosa under pathologic conditions. Namely, one of the first physiologic defense responses of any organ is inflammation that starts with rapid vascular changes (e.g. increased VP and blood flow), followed by cellular events (e.g. infiltration by acute and chronic inflammatory cells). Thus, PG and histamine, by increasing VP create a perivascular edema that dilutes and delays toxic agents reaching the subepithelial capillaries. Otherwise, damaging chemicals may induce severe early vascular injury resulting in blood flow stasis, hypoxia, and necrosis of surrounding epithelial and mesenchymal cells. In this complex response, increased mucus and/or bicarbonate secretion seem to cause luminal dilution of gastrotoxic chemicals that is further reinforced by a perivascular, histodilutional component. This mechanistic explanation would encompass the protective actions of diverse agents as PG, small doses of histamine, motility stimulants, and dilute irritants (i.e. "adaptive cytoprotection"). Thus, although markedly increased VP is pathologic, slight increase in VP seems to be protective, that is, a key element in the complex pathophysiologic response during acute gastroprotection. Over the years, "gastroprotection" was also applied to accelerated healing of chronic gastroduodenal ulcers without reduction of acid secretion. The likely main mechanism here is the binding of angiogenic growth factors (e.g. basic fibroblast growth factor, vascular endothelial growth factor) to the heparin-like structures of sucralfate and sofalcone. Thus, despite intensive research of the last 30 years, gastroprotection is incompletely understood, and we are still far away from effectively treating Helicobacter pylori-negative ulcers and preventing nonsteroidal anti-inflammatory drugs-caused erosions and ulcers in the upper and lower gastrointestinal tract; hence "gastric cytoprotection" research is still relevant.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cytoprotection; Drug Discovery; Gastric Acid; Gastrointestinal Agents; Humans; Prostaglandins; Stomach Ulcer
PubMed: 25521744
DOI: 10.1111/jgh.12735 -
The Cochrane Database of Systematic... Aug 2018Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent progression of chronic kidney disease-mineral and bone disorder (CKD-MBD). This is an update of a review first published in 2011.
OBJECTIVES
The aim of this review was to assess the benefits and harms of phosphate binders for people with CKD with particular reference to relevant biochemical end-points, musculoskeletal and cardiovascular morbidity, hospitalisation, and death.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 12 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or quasi-RCTs of adults with CKD of any GFR category comparing a phosphate binder to another phosphate binder, placebo or usual care to lower serum phosphate. Outcomes included all-cause and cardiovascular death, myocardial infarction, stroke, adverse events, vascular calcification and bone fracture, and surrogates for such outcomes including serum phosphate, parathyroid hormone (PTH), and FGF23.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess evidence certainty. We estimated treatment effects using random-effects meta-analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised MD (SMD) for continuous outcomes.
MAIN RESULTS
We included 104 studies involving 13,744 adults. Sixty-nine new studies were added to this 2018 update.Most placebo or usual care controlled studies were among participants with CKD G2 to G5 not requiring dialysis (15/25 studies involving 1467 participants) while most head to head studies involved participants with CKD G5D treated with dialysis (74/81 studies involving 10,364 participants). Overall, seven studies compared sevelamer with placebo or usual care (667 participants), seven compared lanthanum to placebo or usual care (515 participants), three compared iron to placebo or usual care (422 participants), and four compared calcium to placebo or usual care (278 participants). Thirty studies compared sevelamer to calcium (5424 participants), and fourteen studies compared lanthanum to calcium (1690 participants). No study compared iron-based binders to calcium. The remaining studies evaluated comparisons between sevelamer (hydrochloride or carbonate), sevelamer plus calcium, lanthanum, iron (ferric citrate, sucroferric oxyhydroxide, stabilised polynuclear iron(III)-oxyhydroxide), calcium (acetate, ketoglutarate, carbonate), bixalomer, colestilan, magnesium (carbonate), magnesium plus calcium, aluminium hydroxide, sucralfate, the inhibitor of phosphate absorption nicotinamide, placebo, or usual care without binder. In 82 studies, treatment was evaluated among adults with CKD G5D treated with haemodialysis or peritoneal dialysis, while in 22 studies, treatment was evaluated among participants with CKD G2 to G5. The duration of study follow-up ranged from 8 weeks to 36 months (median 3.7 months). The sample size ranged from 8 to 2103 participants (median 69). The mean age ranged between 42.6 and 68.9 years.Random sequence generation and allocation concealment were low risk in 25 and 15 studies, respectively. Twenty-seven studies reported low risk methods for blinding of participants, investigators, and outcome assessors. Thirty-one studies were at low risk of attrition bias and 69 studies were at low risk of selective reporting bias.In CKD G2 to G5, compared with placebo or usual care, sevelamer, lanthanum, iron and calcium-based phosphate binders had uncertain or inestimable effects on death (all causes), cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. Sevelamer may lead to constipation (RR 6.92, CI 2.24 to 21.4; low certainty) and lanthanum (RR 2.98, CI 1.21 to 7.30, moderate certainty) and iron-based binders (RR 2.66, CI 1.15 to 6.12, moderate certainty) probably increased constipation compared with placebo or usual care. Lanthanum may result in vomiting (RR 3.72, CI 1.36 to 10.18, low certainty). Iron-based binders probably result in diarrhoea (RR 2.81, CI 1.18 to 6.68, high certainty), while the risks of other adverse events for all binders were uncertain.In CKD G5D sevelamer may lead to lower death (all causes) (RR 0.53, CI 0.30 to 0.91, low certainty) and induce less hypercalcaemia (RR 0.30, CI 0.20 to 0.43, low certainty) when compared with calcium-based binders, and has uncertain or inestimable effects on cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. The finding of lower death with sevelamer compared with calcium was present when the analysis was restricted to studies at low risk of bias (RR 0.50, CI 0.32 to 0.77). In absolute terms, sevelamer may lower risk of death (all causes) from 210 per 1000 to 105 per 1000 over a follow-up of up to 36 months, compared to calcium-based binders. Compared with calcium-based binders, lanthanum had uncertain effects with respect to all-cause or cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification and probably had reduced risks of treatment-related hypercalcaemia (RR 0.16, CI 0.06 to 0.43, low certainty). There were no head-to-head studies of iron-based binders compared with calcium. The paucity of placebo-controlled studies in CKD G5D has led to uncertainty about the effects of phosphate binders on patient-important outcomes compared with placebo.It is uncertain whether the effects of binders on clinically-relevant outcomes were different for patients who were and were not treated with dialysis in subgroup analyses.
AUTHORS' CONCLUSIONS
In studies of adults with CKD G5D treated with dialysis, sevelamer may lower death (all causes) compared to calcium-based binders and incur less treatment-related hypercalcaemia, while we found no clinically important benefits of any phosphate binder on cardiovascular death, myocardial infarction, stroke, fracture or coronary artery calcification. The effects of binders on patient-important outcomes compared to placebo are uncertain. In patients with CKD G2 to G5, the effects of sevelamer, lanthanum, and iron-based phosphate binders on cardiovascular, vascular calcification, and bone outcomes compared to placebo or usual care, are also uncertain and they may incur constipation, while iron-based binders may lead to diarrhoea.
Topics: Adult; Aged; Calcium; Calcium Compounds; Cause of Death; Chelating Agents; Chronic Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Disease Progression; Fibroblast Growth Factor-23; Humans; Hypercalcemia; Iron Compounds; Lanthanum; Middle Aged; Parathyroid Hormone; Phosphorus; Polyamines; Randomized Controlled Trials as Topic; Renal Dialysis; Sevelamer
PubMed: 30132304
DOI: 10.1002/14651858.CD006023.pub3