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Frontiers in Oncology 2022This review aimed to comprehensively analyze the safety and efficacy of erdafitinib in treating advanced and metastatic urothelial carcinoma and other solid tumors.
OBJECTIVE
This review aimed to comprehensively analyze the safety and efficacy of erdafitinib in treating advanced and metastatic urothelial carcinoma and other solid tumors.
METHODS
PubMed, Embase, and ClinicalTrials.gov were searched until 10 February 2022. The safety outcome as adverse events and efficacy outcomes, including objective response rate, stable disease rates, and progressive disease rates, were selected and analyzed by comprehensive meta-analysis version 3.0 and STATA 15.0.
RESULTS
The most common all-grade adverse events were hyperphosphatemia, dry mouth, stomatitis, diarrhea, and dysgeusia. The occurrence of ≥3 adverse events was relatively low, and stomatitis and hyponatremia were the most common. Moreover, eye disorders could not be ignored. Efficacy in urothelial carcinoma patients was obviously better than in other solid tumor patients, with a higher objective response rate (0.38 versus 0.10) and lower progressive disease rate (0.26 versus 0.68). All responses occurred in patients with fibroblast growth factor receptor (FGFR) alteration. In those patients, a specific FGFR alteration () was observed to have a maximum response.
CONCLUSION
Erdafitinib has satisfactory clinical activity for metastatic urothelial carcinoma and other solid tumors, while the toxicity is acceptable. With more RCTs and combination therapy trials published, erdafitinib will be applied widely.
PubMed: 36776367
DOI: 10.3389/fonc.2022.907377 -
Journal of Pain and Symptom Management Jan 2023Uremic pruritus (UP) is a chronic disease that can seriously affect the quality of life of dialysis patients. Acupuncture is a non-medication therapy that has been used... (Meta-Analysis)
Meta-Analysis Review
Uremic pruritus (UP) is a chronic disease that can seriously affect the quality of life of dialysis patients. Acupuncture is a non-medication therapy that has been used to treat pruritus disorders. This systematic review aimed to evaluate the efficacy and safety of acupuncture for the treatment of UP. A total of nine Chinese and English databases were searched from their inception to December 31, 2021, and 214 studies were retrieved. Finally, seven randomized controlled trials (n=504) were included in the meta-analysis performed using RevMan V.5.3. Results included effective rate, recurrence rates, and adverse events. Compared with conventional treatment, acupuncture was more effective in treating UP (risk ratio [RR]=1.28, 95% confidence interval [CI]=1.09 to 1.50, P=0.003). The results were consistent after sensitivity analysis (RR=1.38, 95% CI=1.21 to 1.57, P<0.00001). In subgroup analysis, the efficacy rates of acupuncture and medications (oral and topical) were comparable (RR=1.20, 95% CI=0.98 to 1.47, P=0.07). Acupuncture combined with hemodialysis was more effective than hemodialysis alone in relieving pruritus (RR=1.42, 95% CI=1.18 to 1.72, P=0.0002). Adverse events were reported in only three studies, including one case of hyperphosphatemia in the medications group (RR=0.29, 95% CI=0.01 to 7.06, P=0.45). None of the studies reported recurrence rates. In conclusion, acupuncture is a safe treatment modality for patients with UP receiving hemodialysis that can effectively improve UP symptoms, and acupuncture in combination with hemodialysis has more efficacy than hemodialysis alone in improving the UP symptoms.
Topics: Humans; Quality of Life; Renal Dialysis; Acupuncture Therapy; Pruritus
PubMed: 36055470
DOI: 10.1016/j.jpainsymman.2022.08.017 -
Journal of Bone and Mineral Research :... Oct 2022Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism due to activating variants of the calcium-sensing receptor gene (CASR). Inherited or...
Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism due to activating variants of the calcium-sensing receptor gene (CASR). Inherited or de novo activating variants of the CASR alter the set point for extracellular calcium, resulting in inadequate parathyroid hormone (PTH) secretion and inappropriate renal calcium excretion leading to hypocalcemia and hypercalciuria. Conventional therapy includes calcium and activated vitamin D, which can worsen hypercalciuria, resulting in renal complications. A systematic literature review, using published reports from 1994 to 2021, was conducted to catalog CASR variants, to define the ADH1 clinical spectrum, and to determine the effect of treatment on patients with ADH1. There were 113 unique CASR variants reported, with a general lack of genotype/phenotype correlation. Clinical data were available in 191 patients; 27% lacked symptoms, 32% had mild/moderate symptoms, and 41% had severe symptoms. Seizures, the most frequent clinical presentation, occurred in 39% of patients. In patients with blood and urine chemistries available at the time of diagnosis (n = 91), hypocalcemia (99%), hyperphosphatemia (59%), low PTH levels (57%), and hypercalciuria (34%) were observed. Blood calcium levels were significantly lower in patients with severe symptoms compared with asymptomatic patients (6.8 ± 0.7 versus 7.6 ± 0.7 mg/dL [mean ± SD]; p < 0.0001), and the age of presentation was significantly lower in severely symptomatic patients (9.1 ± 15.0 versus 19.3 ± 19.4 years; p < 0.01). Assessments for complications including nephrocalcinosis, nephrolithiasis, renal impairment, and brain calcifications in 57 patients on conventional therapy showed that 75% had at least one complication. Hypercalciuria was associated with nephrocalcinosis, nephrolithiasis, renal impairment, or brain calcifications (odds ratio [OR] = 9.3; 95% confidence interval [CI] 2.4-37.2; p < 0.01). In 27 patients with urine calcium measures before and after starting conventional therapy, the incidence of hypercalciuria increased by 91% (p < 0.05) after therapy initiation. ADH1 is a condition often associated with severe symptomatology at presentation with an increase in the risk of renal complications after initiation of conventional therapy. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Hypercalciuria; Hypocalcemia; Receptors, Calcium-Sensing; Calcium; Nephrocalcinosis; Hypoparathyroidism; Parathyroid Hormone; Nephrolithiasis; Vitamin D
PubMed: 35879818
DOI: 10.1002/jbmr.4659 -
Frontiers in Medicine 2022Serum phosphate level is often deranged during critical illness. Hyperphosphatemia, as a marker of disease severity, attracts more and more attention. This study aimed...
INTRODUCTION
Serum phosphate level is often deranged during critical illness. Hyperphosphatemia, as a marker of disease severity, attracts more and more attention. This study aimed to evaluate the impact of hyperphosphatemia on clinical outcomes in critically ill patients.
METHODS
We searched for relevant studies in PubMed, EMBASE, and the Cochrane database up to Jan 10, 2022. Two authors independently screened studies, extracted data, and assessed the study quality. Meta-analyses were performed to determine hyperphosphatemia prevalence and evaluate its relationship with prognosis and important clinical outcomes. We also conducted subgroup analysis and sensitivity analyses to explore the sources of heterogeneity.
RESULTS
Ten studies with 60,358 patients met the inclusion criteria. These studies were moderate to high quality. The median prevalence of hyperphosphatemia was 30% (range from 5.6 to 45%). Patients with hyperphosphatemia had a significantly higher risk of all-cause mortality than those without (OR 2.85; 95% CI, 2.35 to 3.38, < 0.0001). Subgroup analyses, sensitivity analyses, and regression analyses further confirmed these results. In addition, patients with hyperphosphatemia required more CRRT (OR 4.96; 95% CI, 2.43 to 10.2, < 0.0001) but not significantly increased duration of mechanical ventilation (mean difference, MD 0.13, 95% CI -0.04 to 0.30; = 0.138), length of stay in intensive care unit (ICU) (SMD 0.164 day, 95% CI -0.007 to 0.335; = 0.06), and length of stay in hospital (SMD 0.005 day, 95% CI -0.74 to 0.75; = 0.99).
CONCLUSIONS
Our results indicated that hyperphosphatemia was associated with all-cause mortality in critically ill patients. However, due to the retrospective design of the included studies, more prospective, well-designed research is required in the future.
SYSTEMATIC REVIEW REGISTRATION
[https://doi.org/10.37766/inplasy2021.12.0130], identifier [INPLASY2021120130].
PubMed: 35665344
DOI: 10.3389/fmed.2022.870637 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2022Enemas containing phosphate are widely prescribed and may cause important adverse effects. A systemic review published in 2007 reported the literature on the adverse...
INTRODUCTION
Enemas containing phosphate are widely prescribed and may cause important adverse effects. A systemic review published in 2007 reported the literature on the adverse effects of phosphate enemas from January 1957 to March 2007 and identified 12 deaths. These were thought due to electrolyte disturbances, heart failure and kidney injury. These data raised concerns about the use of phosphate enemas in routine practice. Newer osmotic-based enema alternatives are now available that do not contain absorbable ions. We sought to review the literature since this review and evaluate the latest data on the toxicity of phosphate-containing enemas. To gain a fuller picture we included case series and larger studies as well as case reports.
OBJECTIVES
To review the toxicity of phosphate enemas, particularly with respect to acute metabolic consequences and their associated clinical features. To identify risk factors for metabolic toxicity and consider whether phosphate enemas should be relatively contra-indicated in specific patient groups.
METHODS
A systematic literature review was conducted in PubMed, Google Scholar, and Cochrane Reviews (2005-2021) using the search terms 'phosphate enema or sodium phosphate enema' or 'phosphate-based enema' or (phosphate AND enema) or (Fleet AND enema) or 'sodium phosphate laxatives' or 'sodium phosphate catharsis' or 'sodium phosphate cathartic'. Relevant papers were read, and data were extracted.
RESULTS
The searches identified 489 papers of which 25 were relevant: seven papers were case reports or small case series of metabolic abnormalities from the use of phosphate enemas in nine children, six were case reports on 16 adults. Nine papers were large case series or clinical studies that included data on systemic metabolic effects, of varying size from 24 healthy volunteers to a cohort of 70,499 patients. Case reports identified seven adult deaths but none in children. Children most often presented with decreased consciousness (6/9), and tetany (4/9). In adults overall only five cases had clinical features reported, hypotension was seen in four and QT prolongation in two. Treatment was generally symptomatic, with intravenous fluid and calcium salts for electrolyte changes and hypocalcaemia, and vasopressors for severe hypotension. Haemodialysis was used in three children and peritoneal dialysis in one, all of whom survived. In adults, haemodialysis did not prevent death in two of four cases in whom it was used. Common factors underlying toxicity were inappropriately high phosphate dose, or enema retention, both resulting in greater absorption of phosphate. Associated pre-disposing conditions included Hirschsprung disease in children and co-morbidity and renal impairment (2/5) in older adults. Absolute reported changes in serum phosphate or calcium were not accurate indicators of outcome. Larger case series and clinical trials confirm an acute effect of phosphate enemas on serum phosphate, which was related to both dose and retention time. These effects were not seen with non-phosphate preparations. In these cases series, adverse events were rarely reported.
CONCLUSION
Phosphate enemas are potentially toxic, particularly in young children with Hirschsprung disease and in the elderly with co-morbidity. Raised awareness of the risk of phosphate enemas is still required. Other less toxic enema preparations are available and should be considered in patients at extremes of age. If phosphate enemas are the only clinical option careful monitoring of biochemical sequelae should be undertaken.
Topics: Aged; Calcium; Child; Child, Preschool; Enema; Hirschsprung Disease; Humans; Hypotension; Laxatives; Phosphates
PubMed: 35510830
DOI: 10.1080/15563650.2022.2054424 -
Journal of Pharmacy & Pharmaceutical... 2022This narrative review explores the currently published studies that have evaluated tenapanor for the treatment of hyperphosphatemia in end-stage kidney disease (ESKD)...
PURPOSE
This narrative review explores the currently published studies that have evaluated tenapanor for the treatment of hyperphosphatemia in end-stage kidney disease (ESKD) patients on hemodialysis. This medication's new phosphate lowering mechanism of action reduces intestinal phosphate absorption predominantly through reduction of passive paracellular phosphate flux by inhibition of the sodium/hydrogen exporter isoform 3 (NHE3). Tenapanor additionally prevents active transcellular phosphate absorption compensation by decreasing the expression of sodium phosphorus 2b transport protein (NaPi2b).
METHODS
A comprehensive search of the literature was conducted using PubMed and ClinicalTrials.gov search engines. The search term "tenapanor hyperphosphatemia" was used for study retrieval. Results were limited to studies published in the English language and excluded review articles. Human, animal, and in vitro studies were included. No date range was specified.
RESULTS
A total of 11 primary studies were identified and included in this review, the largest human study of which enrolled 236 patients. Each study is presented in table format along with measured end points.
CONCLUSIONS
Tenapanor is the first drug in its class that lowers hyperphosphatemia in ESKD patients through a novel mechanism of action involving paracellular inactive transport. Although more studies are needed, early results indicate that tenapanor may have a place in managing hyperphosphatemia in ESKD patients both as monotherapy and as an adjunct to existing phosphate binder therapy.
Topics: Animals; Biological Transport, Active; Cytochrome P-450 Enzyme Inhibitors; Drug Interactions; Humans; Hyperphosphatemia; Intestinal Absorption; Isoquinolines; Kidney Failure, Chronic; Phosphates; Rats; Sodium-Hydrogen Exchanger 3; Sulfonamides
PubMed: 35041802
DOI: 10.18433/jpps32284 -
Digestive Endoscopy : Official Journal... Jul 2022We conducted a systematic review and meta-analysis of population-based studies to explore pooled prevalence and magnitude of electrolyte changes after bowel preparation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND STUDY AIMS
We conducted a systematic review and meta-analysis of population-based studies to explore pooled prevalence and magnitude of electrolyte changes after bowel preparation for colonoscopy based on the most recent guidelines.
PATIENTS AND METHODS
PubMed and Cochrane were queried for population-based studies examining changes in electrolyte values after bowel preparation, published by July 1, 2021. We report prevalences of serum hypokalemia, hyponatremia, hyperphosphatemia, and hypocalcemia after bowel preparation and changes in mean electrolyte values after vs. before bowel preparation using sodium phosphate (NaP) and polyethylene glycol (PEG).
RESULTS
Thirteen studies met the inclusion criteria; 2386 unique patients were included. Overall, hypokalemia was found in 17.2% (95% CI 6.7, 30.9) in the NaP group vs. 4.8% (95% CI 0.27, 13.02) in the PEG group. The magnitude of potassium decrease after NaP bowel preparation was significantly increased compared to PEG (mean difference -0.38; 95% CI -0.49 to -0.27, P < 0.001). No study reported on major complications.
CONCLUSIONS
Hypokalemia was found in 17.2% of patients after bowel preparation with NaP and in 4.8% of patients with PEG, a finding that is clinically relevant with respect to choosing the type of bowel preparation. The magnitude of the potassium decrease after NaP was significantly higher compared to PEG. These data provide the evidence that supports the recommendation of the European Society of Gastrointestinal Endoscopy against routine use of NaP for bowel preparation.
Topics: Cathartics; Colonoscopy; Electrolytes; Humans; Hypokalemia; Polyethylene Glycols; Potassium
PubMed: 35037327
DOI: 10.1111/den.14237 -
Journal of the American Society of... Jan 2022Benefits of phosphate-lowering interventions on clinical outcomes in patients with CKD are unclear; systematic reviews have predominantly involved patients on dialysis.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Benefits of phosphate-lowering interventions on clinical outcomes in patients with CKD are unclear; systematic reviews have predominantly involved patients on dialysis. This study aimed to summarize evidence from randomized controlled trials (RCTs) concerning benefits and risks of noncalcium-based phosphate-lowering treatment in nondialysis CKD.
METHODS
We conducted a systematic review and meta-analyses of RCTs involving noncalcium-based phosphate-lowering therapy compared with placebo, calcium-based binders, or no study medication, in adults with CKD not on dialysis or post-transplant. RCTs had ≥3 months follow-up and outcomes included biomarkers of mineral metabolism, cardiovascular parameters, and adverse events. Outcomes were meta-analyzed using the Sidik-Jonkman method for random effects. Unstandardized mean differences were used as effect sizes for continuous outcomes with common measurement units and Hedge's g standardized mean differences (SMD) otherwise. Odds ratios were used for binary outcomes. Cochrane risk of bias and GRADE assessment determined the certainty of evidence.
RESULTS
In total, 20 trials involving 2498 participants (median sample size 120, median follow-up 9 months) were eligible for inclusion. Overall, risk of bias was low. Compared with placebo, noncalcium-based phosphate binders reduced serum phosphate (12 trials, weighted mean difference -0.37; 95% CI, -0.58 to -0.15 mg/dl, low certainty evidence) and urinary phosphate excretion (eight trials, SMD -0.61; 95% CI, -0.90 to -0.31, low certainty evidence), but resulted in increased constipation (nine trials, log odds ratio [OR] 0.93; 95% CI, 0.02 to 1.83, low certainty evidence) and greater vascular calcification score (three trials, SMD, 0.47; 95% CI, 0.17 to 0.77, very low certainty evidence). Data for effects of phosphate-lowering therapy on cardiovascular events (log OR, 0.51; 95% CI, -0.51 to 1.17) and death were scant.
CONCLUSIONS
Noncalcium-based phosphate-lowering therapy reduced serum phosphate and urinary phosphate excretion, but there was an unclear effect on clinical outcomes and intermediate cardiovascular end points. Adequately powered RCTs are required to evaluate benefits and risks of phosphate-lowering therapy on patient-centered outcomes.
Topics: Chelating Agents; Ferric Compounds; Humans; Hyperphosphatemia; Lanthanum; Phosphates; Renal Insufficiency, Chronic; Sevelamer
PubMed: 34645696
DOI: 10.1681/ASN.2021040554 -
Journal of Nephrology Mar 2022Besides reducing hyperphosphatemia in chronic kidney disease (CKD) patients, phosphate lowering agents might provide beneficial effects on clinical and laboratory... (Meta-Analysis)
Meta-Analysis
The impact of phosphate lowering agents on clinical and laboratory outcomes in chronic kidney disease patients: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Besides reducing hyperphosphatemia in chronic kidney disease (CKD) patients, phosphate lowering agents might provide beneficial effects on clinical and laboratory parameters. This meta-analysis was conducted to comprehensively examine the impact of all phosphate lowering agents on various aspects of clinical and laboratory outcomes in CKD patients.
METHOD
A systematic literature search was performed in MEDLINE, Scopus, and the Cochrane Register of Controlled Trials until July 2020 to identify randomized controlled trials (RCTs) which compared the effects of each phosphate lowering agent with controls, comprising placebo and all other phosphate lowering agents. Various clinical and laboratory outcomes were analyzed. Random effects model was used to compute the standardized mean difference for continuous variables and the risk ratio (RR) for binary variables.
RESULTS
This meta-analysis included 127 RCTs with 20,215 patients. Sevelamer and lanthanum significantly reduced all-cause mortality (RR 0.610, 95% CI 0.401-0.929 and 0.467, 95% CI 0.337-0.647, respectively) but not cardiovascular (CV) mortality or CV events. Hospitalization rates were significantly diminished by sevelamer (RR 0.527; 95% CI 0.308-0.902). Certain phosphate lowering agents improved biochemical parameters including serum phosphate, calcium, coronary artery calcium scores, fibroblast growth factor-23, bone biomarkers, and lipid profiles. Intact parathyroid hormone and bone mineral density were not significantly changed.
CONCLUSIONS
In addition to decreasing serum phosphate levels, various beneficial effects on clinical and laboratory parameters of phosphate lowering agents might play potential roles in diminishing morbidity and mortality in CKD patients.
Topics: Humans; Hyperphosphatemia; Phosphates; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sevelamer
PubMed: 34061337
DOI: 10.1007/s40620-021-01065-3 -
The European Journal of Health... Jun 2021Uncontrolled hyperphosphatemia in chronic kidney disease (CKD) patients commonly results in vascular calcification leading to increased risk of cardiovascular disease.... (Meta-Analysis)
Meta-Analysis
Evaluation of the cost-utility of phosphate binders as a treatment option for hyperphosphatemia in chronic kidney disease patients: a systematic review and meta-analysis of the economic evaluations.
BACKGROUND
Uncontrolled hyperphosphatemia in chronic kidney disease (CKD) patients commonly results in vascular calcification leading to increased risk of cardiovascular disease. Phosphate binders (PBs) are used for hyperphosphatemia and can be calcium-based (CBPBs) or non-calcium-based (NCBPBs), the latter being more expensive than CBPBs. In this study, we used meta-analysis approaches to assess the cost-utility of PBs for hyperphosphatemia in CKD patients.
METHODS
Relevant studies published prior to June 2019 were identified from PubMed, Scopus, the Cochrane Library, the National Health Service Economic Evaluation Database, and the Cost-Effectiveness Analysis Registry. Studies were eligible if they included CKD patients with hyperphosphatemia, compared any PBs and reported economic outcomes. Meta-analysis was applied to pool incremental net benefit (INB) across studies stratified by country income.
RESULTS
A total of 25 studies encompassing 32 comparisons were eligible. Lanthanum carbonate, a NCBPB, was a more cost-effective option than CBPBs in high-income countries (HICs), with a pooled INB of $3984.4 (599.5-7369.4), especially in pre-dialysis patients and used as a second-line option with INBs of $4860.2 (641.5-9078.8), $4011.0 (533.7-7488.3), respectively. Sevelamer, also a NCBPB, was not more cost-effective as a first-line option compared to CBPBs with a pooled INB of $6045.8 (- 23,453.0 to 35,522.6) and $34,168.9 (- 638.0 to 68,975.7) in HICs and upper middle-income countries, respectively.
CONCLUSIONS
Lanthanum carbonate was significantly more cost-effective than CBPBs as a second-line option for hyperphosphatemia in pre-dialysis patients in HICs. However, the use of sevelamer is not more cost-effective as a first-line option compared to CBPBs.
Topics: Cost-Benefit Analysis; Humans; Hyperphosphatemia; Phosphates; Renal Dialysis; Renal Insufficiency, Chronic; State Medicine
PubMed: 33677736
DOI: 10.1007/s10198-021-01275-3