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Acta Obstetricia Et Gynecologica... Sep 2021Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the...
INTRODUCTION
Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the sperm DNA or through fetal exposure caused by a presence in the seminal fluid. This systematic overview summarizes existing literature on the spermatotoxic and genotoxic potentials of methotrexate (MTX), a drug widely used to treat rheumatic and dermatologic diseases, and mycophenolate mofetil (MMF), which alone or supplemented with ganciclovir (GCV) may be crucial for the survival of organ transplants.
MATERIAL AND METHODS
The systematic overview was performed in accordance with the PRISMA guidelines: A systematic literature search of the MEDLINE and Embase databases was done using a combination of relevant terms to search for studies on spermatotoxic or genotoxic changes related to treatment with MTX, GCV or MMF. The search was restricted to English language literature, and to in vivo animal studies (mammalian species) and clinical human studies.
RESULTS
A total of 102 studies were identified, hereof 25 human and 77 animal studies. For MTX, human studies of immunosuppressive dosages show transient effect on sperm quality parameters, which return to reference values within 3 months. No human studies have investigated the sperm DNA damaging effect of MTX, but in other organs the genotoxic effects of immunosuppressive doses of MTX are fluctuating. In animals, immunosuppressive and cytotoxic doses of MTX adversely affect sperm quality parameters and show widespread genotoxic damages in various organs. Cytotoxic doses transiently change the DNA material in all cell stages of spermatogenesis in rodents. For GCV and MMF, data are limited and the results are indeterminate, for which reason spermatotoxic and genotoxic potentials cannot be excluded.
CONCLUSIONS
Data from human and animal studies indicate transient spermatotoxic and genotoxic potentials of immunosuppressive and cytotoxic doses of MTX. There are a limited number of studies investigating GCV and MMF.
Topics: DNA Damage; Ganciclovir; Humans; Immunosuppressive Agents; Male; Methotrexate; Mycophenolic Acid; Spermatozoa
PubMed: 33755191
DOI: 10.1111/aogs.14151 -
The Journal of Urology Nov 2023Ureteral stents are commonly used for the treatment of ureteral obstruction, most often urolithiasis. Their use may be associated with significant bothersome symptoms... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Ureteral stents are commonly used for the treatment of ureteral obstruction, most often urolithiasis. Their use may be associated with significant bothersome symptoms and discomfort. Prior studies have examined the effects of various medication regimens on ureteral stent symptoms. This study utilized Bayesian network meta-analysis to analyze all available evidence on the pharmacological management of ureteral stent-related symptoms.
MATERIALS AND METHODS
In December 2022 a systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines on randomized prospective studies on pharmacological management of ureteral stent-related symptoms reporting outcomes using the Ureteral Stent Symptom Questionnaire score on urinary symptoms and pain. The data were analyzed in Review Manager 5.3 and R Studio where a Bayesian network meta-analysis was performed. Treatments were ranked using surface under the cumulative ranking curve and mean difference vs placebo with 95% credible intervals.
RESULTS
A total of 26 studies were analyzed. These were used to build networks which were modeled to run 100,000 Markov Chain Montecarlo simulations each. Drug-class analysis revealed the most effective class for each domain: for urinary symptoms, sexual performance, general health, and work performance-combined α-blocker and anticholinergic and phosphodiesterase 5 inhibitors; for pain-combined anticholinergic and pregabalin. The following were the most effective drugs and dosages for specific symptoms: for urinary symptoms-combined silodosin 8 mg+solifenacin 10 mg; for pain-combined silodosin 8 mg+solifenacin 10 mg; for sexual performance-tadalafil 5 mg. Combined silodosin 8 mg+solifenacin 10 mg+tadalafil 5 mg has the best general health scores while solifenacin 10 mg had the best work experience scores.
CONCLUSIONS
This network meta-analysis demonstrated that the most effective drug therapy is different for each symptom domain. It is important to consider a patient's chief complaint and domains in order to ascertain the optimal medication regimen for each patient. Further iterations of this analysis can be strengthened by trials that directly compare more of these drugs instead of relying on indirect evidence.
Topics: Humans; Solifenacin Succinate; Tadalafil; Network Meta-Analysis; Prospective Studies; Bayes Theorem; Quality of Life; Ureter; Pain; Cholinergic Antagonists; Stents
PubMed: 37428119
DOI: 10.1097/JU.0000000000003616 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
International Immunopharmacology Apr 2023This systematic review aims to show the efficiency of Erenumab in the preventive therapy of episodic and chronic migraine, which is still under research. (Review)
Review
OBJECTIVE
This systematic review aims to show the efficiency of Erenumab in the preventive therapy of episodic and chronic migraine, which is still under research.
BACKGROUND
Migraine is a chronic neurovascular disorder that causes disability and a social burden. There are various medications used for migraine prevention regimens, most of which have unwanted side effects and aren't often quite effective. Erenumab is a monoclonal antibody that targets calcitonin gene-related peptide receptors and was recently approved by the Food and Drug Administration for migraine prevention.
METHODS
For this systematic review, we searched through Scopus and PubMed databases using "Erenumab" or "AMG 334" and "migraine" as keywords, and all the studies from 2016 to March 18, 2022, were included. Original English articles assessing any outcomes referring to the efficacy of Erenumab in migraine headache treatment were included in this study.
RESULTS
We found 53 out of 605 papers eligible to be investigated. Erenumab in both dosages of 70 mg and 140 mg could decrease the mean of monthly migraine days and monthly acute migraine-specific medication days. Erenumab also has a higher rate of ≥ 50 %, ≥ 75 %, and 100 % reduction in monthly migraine days from the baseline in different regions. The efficacy of Erenumab was initiated in the first week of administration and sustained throughout and after treatment. Erenumab was also potent in the treatment of migraine with allodynia, aura, prior preventive therapy failure, medication overuse headache, and menstrual migraine. Erenumab also had favorable outcomes in combination therapy with other preventive drugs like Onabotulinumtoxin-A.
CONCLUSION
Erenumab had remarkable efficacy in the short and long-term treatment of episodic and chronic migraine, notably the patients with difficult-to-treat migraine headaches.
Topics: Humans; Calcitonin Gene-Related Peptide Receptor Antagonists; Migraine Disorders; Antibodies, Monoclonal; Chronic Disease; Combined Modality Therapy
PubMed: 37012858
DOI: 10.1016/j.intimp.2022.109366 -
Medicine Nov 2023This systematic review explores the most current evidence regarding the mechanisms of neuropathic pain in patients with different types of diabetes and how this pain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review explores the most current evidence regarding the mechanisms of neuropathic pain in patients with different types of diabetes and how this pain affects different functional and structural components of the neuroanatomical pain pathways. The review also seeks to provide guidelines for the best approach and treatment for patients experiencing this type of pain. The objective is to determine the effectiveness of alpha-lipoic acid (ALA) in improving functional and symptomatic outcomes in patients with diabetes mellitus type I and type II.
OBJECTIVE
To determine the effectiveness of alpha-lipoic acid (ALA) in improving functional and symptomatic outcomes in patients with diabetes mellitus type I and type II.
METHODS
We systematically search MEDLINE (via PubMed), EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, and Web of Science databases.
RESULTS
The findings of this review show that different forms of ALA do not present statistically significant changes for any of the scales included, including total symptom score (standardized mean difference [SMD] = -3.59, confidence interval [CI] = -4.16 to -3.02, and P < .00001), neuropathy impairment score (SMD = -1.42, CI = -3.68 to 0.84, and P = .22), and neuropathy symptom checklist (SMD = -0.09, CI = -0.15 to -0.02, and P = .01).
CONCLUSION
In comparison to the use of a placebo, the findings suggest that ALA does not exhibit significant differences in terms of pain reduction and different functional scales. Moreover, no specific dosages are identified to support the use of ALA for the reduction of neuropathic pain.
Topics: Humans; Thioctic Acid; Diabetes Mellitus, Type 2; Neuralgia; Antioxidants; Diabetes Mellitus, Type 1
PubMed: 37933068
DOI: 10.1097/MD.0000000000035368 -
Clinical Therapeutics Nov 2020This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis... (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis (TB), evaluates whether the current INH dose regimen is appropriate in patients with TB, and evaluates the impact of N-acetyl-transferase-2 (NAT2) status on the PK properties of INH.
METHODS
A systematic approach was conducted to find studies with relevant INH PK data published in the English language up to February 2018. The PK properties of INH were extracted with their respective INH dosages and were dose normalized to allow a fair comparison between healthy volunteers and patients with TB. Meta-analysis was then performed for the C and AUC estimates for all INH dosages.
FINDINGS
Ninety studies were included in this systematic review. TB status significantly affected the INH C and AUC estimates. In healthy volunteers, the dose-normalized INH C and AUC were statistically higher than those of patients with TB. No significant differences were found in dose-normalized C and AUC between adults with TB and adults with TB/HIV; however, the AUC in pediatric patients was significantly different between patients with TB and patients with TB/HIV. In addition, no significance was observed comparing the dose-normalized C and AUC of pediatric patients with TB and TB/HIV with their respective adult counterparts. Dose-normalized INH C and AUC in patients with fast and intermediate NAT2 were significantly lower than in patients with slow NAT2.
IMPLICATIONS
The current recommended dosages of INH were found to produce less drug exposure in patients with TB when compared with healthy volunteers. NAT2 polymorphism greatly impacts the PK properties of INH; hence, testing for acetylator status is highly recommended, and therapeutic drug monitoring would help reduce INH toxicity.
Topics: Adult; Antitubercular Agents; Arylamine N-Acetyltransferase; Drug Monitoring; Humans; Isoniazid; Tuberculosis
PubMed: 33032843
DOI: 10.1016/j.clinthera.2020.09.009 -
Obesity Reviews : An Official Journal... Jan 2023This study aimed to investigate the prevalence of anemia and related nutrient deficiencies after sleeve gastrectomy (SG). Four online databases were searched for... (Meta-Analysis)
Meta-Analysis Review
This study aimed to investigate the prevalence of anemia and related nutrient deficiencies after sleeve gastrectomy (SG). Four online databases were searched for relevant articles. Thirty-one studies with 7639 patients were included in the meta-analysis. The pooled anemia prevalence was 7%, 6%, 9%, 10%, 12%, 25%, 20%, and 18% at baseline, 3 months, 6 months, 12 months, 24 months, 36 months, 48 months, and 60 months, respectively. Although the prevalence of vitamin B12 and folate deficiencies remained low postoperatively, the prevalence of ferritin deficiency steadily increased from 6% at baseline to 27% at 60 months. The prevalence of serum iron deficiency decreased from 13% at baseline to 6% at 24 months and increased to 20% at 60 months. Anemia and ferritin deficiency were strongly correlated (Pearson correlation coefficient = 0.774, p = 0.041). Subgroup analysis suggested that age ≤40 years, preoperative anemia, and insufficient iron supplementations were high-risk factors for postoperative anemia. SG is associated with an increased risk of anemia and decreased iron storage over long-term observation. Routine iron supplementations may reduce anemia after SG; however, the dosages recommended by current guidelines may be insufficient. More strict monitoring schedules and supplementation strategies should be established for the timely detection and management of postoperative anemia.
Topics: Humans; Adult; Obesity, Morbid; Prevalence; Gastrectomy; Anemia; Ferritins; Iron; Nutrients
PubMed: 36323610
DOI: 10.1111/obr.13516 -
European Archives of... Mar 2023To investigate the dosages of swallowing exercises reported in intervention studies on post-stroke dysphagia through systematic review. (Review)
Review
PURPOSE
To investigate the dosages of swallowing exercises reported in intervention studies on post-stroke dysphagia through systematic review.
METHODS
Five electronic databases were searched from inception until February 2022 with reference tracing of included studies. Studies were included, where adults with post-stroke dysphagia received rehabilitative, behavioural swallowing exercises, pre/post outcomes were reported, and intervention dosage was described in detail, including frequency, intensity, time, and type of exercise. Two reviewers independently screened studies and rated quality using ASHA Levels of Evidence tool. Data was tabulated and narratively described.
RESULTS
54 studies were included with a total 1501 participants. Studies included 28 randomised controlled trials, 8 non-randomised controlled trials, 12 pre/post studies, 3 retrospective case controls and 3 case studies. Results showed inconsistent reporting of intervention dosage, with intensity the least consistently reported dosage component. While swallowing intervention was most commonly provided five times per week for four weeks, there was a wide breadth of type, frequency, intensity and duration of swallowing exercises reported. Dosage under-reporting and variation was particularly observed in "standard care" co-interventions or control groups. Study strengths included following PRISMA guidelines, providing a comprehensive review of swallowing exercise methodology and dosages, and including non-English studies. The limitation was lack of meta-analysis due to the heterogeneity of included studies.
CONCLUSIONS
Dosages of swallowing exercises are inconsistently reported and vary significantly in post-stroke dysphagia studies. Results indicate the need for consistent and comprehensive dosage reporting in dysphagia studies, and for further research into evidence-based principles to optimise swallowing exercise dosages.
SYSTEMATIC REVIEW REGISTRATION NUMBER
131294.
Topics: Adult; Humans; Deglutition Disorders; Deglutition; Stroke Rehabilitation; Retrospective Studies; Stroke
PubMed: 36471047
DOI: 10.1007/s00405-022-07735-7 -
Journal of Cardiac Failure Jul 2023Traditional approaches to guideline-directed medical therapy (GDMT) management often lead to delayed initiation and titration of therapies in patients with heart... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Traditional approaches to guideline-directed medical therapy (GDMT) management often lead to delayed initiation and titration of therapies in patients with heart failure. This study sought to characterize alternative models of care involving nonphysician provider-led GDMT interventions and their associations with therapy use and clinical outcomes.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies comparing nonphysician provider-led GDMT initiation and/or uptitration interventions vs usual physician care (PROSPERO ID: CRD42022334661). We queried PubMed, Embase, the Cochrane Library, and the World Health Organization International Clinical Trial Registry Platform for peer-reviewed studies from database inception to July 31, 2022. In the meta-analysis, we used RCT data only and leveraged random-effects models to estimate pooled outcomes. Primary outcomes were GDMT initiation and titration to target dosages by therapeutic class. Secondary outcomes included all-cause mortality and HF hospitalizations.
RESULTS
We reviewed 33 studies, of which 17 (52%) were randomized controlled trials with median follow-ups of 6 months; 14 (82%) trials evaluated nurse interventions, and the remainder assessed pharmacists' interventions. The primary analysis pooled data from 16 RCTs, which enrolled 5268 patients. Pooled risk ratios (RR) for renin-angiotensin system inhibitor (RASI) and beta-blocker initiation were 2.09 (95% CI 1.05-4.16; I = 68%) and 1.91 (95% CI1.35-2.70; I = 37%), respectively. Outcomes were similar for uptitration of RASI (RR 1.99, 95% CI 1.24-3.20; I = 77%) and beta-blocker (RR 2.22, 95% CI 1.29-3.83; I = 66%). No association was found with mineralocorticoid receptor antagonist initiation (RR 1.01, 95% CI 0.47-2.19). There were lower rates of mortality (RR 0.82, 95% CI 0.67-1.04; I = 12%) and hospitalization due to HF (RR 0.80, 95% CI 0.63-1.01; I = 25%) across intervention arms, but these differences were small and not statistically significant. Prediction intervals were wide due to moderate-to-high heterogeneity across trial populations and interventions. Subgroup analyses by provider type did not show significant effect modification.
CONCLUSIONS
Pharmacist- and nurse-led interventions for GDMT initiation and/or uptitration improved guideline concordance. Further research evaluating newer therapies and titration strategies integrated with pharmacist- and/or nurse-based care may be valuable.
Topics: Humans; Heart Failure; Pharmacists; Nurse's Role; Antihypertensive Agents; Adrenergic beta-Antagonists
PubMed: 37004867
DOI: 10.1016/j.cardfail.2023.03.012 -
Journal of the Neurological Sciences Jul 2023The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available... (Review)
Review
The prevalences of polyneuropathy and epilepsy are higher in people living with Parkinson's disease (PwPD) when compared to older adults. Vitamin B6 is widely available and affordable. PwPD are at higher risk of having abnormal serum levels of vitamin B6, which are associated with polyneuropathy and epilepsy that are potentially preventable and treatable. Potential contributors to abnormal B6 levels in PwPD include age, dietary habits, vitamin supplement misuse, gastrointestinal dysfunction and complex interactions with levodopa. The literature on the potential consequences of abnormal B6 levels in PwPD is limited by a small number of observational studies focused on polyneuropathy and epilepsy. Abnormal B6 levels have been reported in 60 of 145 PwPD (41.4% relative frequency). Low B6 levels were reported in 52 PwPD and high B6 levels were reported in 8 PwPD. There were 14 PwPD, polyneuropathy and low B6. There were 4 PwPD, polyneuropathy and high B6. There were 4 PwPD, epilepsy and low B6. Vitamin B6 level was low in 44.6% of PwPD receiving levodopa-carbidopa intestinal gel and in 30.1% of PwPD receiving oral levodopa-carbidopa. In almost all studies reporting low B6 in PwPD receiving oral levodopa-carbidopa, the dose of levodopa was ≥1000 mg/day. Rigorous epidemiological studies will clarify the prevalence, natural history and clinical relevance of abnormal serum levels of vitamin B6 in PwPD. These studies should account for diet, vitamin supplement use, gastrointestinal dysfunction, concurrent levels of vitamin B12, folate, homocysteine and methylmalonic acid, formulations and dosages of levodopa and other medications commonly used in PwPD.
Topics: Humans; Aged; Levodopa; Parkinson Disease; Carbidopa; Antiparkinson Agents; Vitamin B 6; Polyneuropathies; Vitamin B 12; Epilepsy; Vitamins
PubMed: 37210937
DOI: 10.1016/j.jns.2023.120690