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Annals of the Rheumatic Diseases Aug 2017The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new...
The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
Topics: Angiotensin-Converting Enzyme Inhibitors; Delphi Technique; Endothelin Receptor Antagonists; Europe; Fingers; Fluoxetine; Gastrointestinal Diseases; Glucocorticoids; Hematopoietic Stem Cell Transplantation; Humans; Hypertension, Pulmonary; Kidney Diseases; Lung Diseases; Phosphodiesterase 5 Inhibitors; Prostaglandins I; Pyrazoles; Pyrimidines; Raynaud Disease; Rheumatology; Scleroderma, Systemic; Selective Serotonin Reuptake Inhibitors; Ulcer
PubMed: 27941129
DOI: 10.1136/annrheumdis-2016-209909 -
Molecular Autism Mar 2022There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is still no approved medication for the core symptoms of autism spectrum disorder (ASD). This network meta-analysis investigated pharmacological and dietary-supplement treatments for ASD.
METHODS
We searched for randomized-controlled-trials (RCTs) with a minimum duration of seven days in ClinicalTrials.gov, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (from inception up to July 8, 2018), CENTRAL and PubMed (up to November 3, 2021). The co-primary outcomes were core symptoms (social-communication difficulties-SCD, repetitive behaviors-RB, overall core symptoms-OCS) measured by validated scales and standardized-mean-differences (SMDs). Associated symptoms, e.g., irritability/aggression and attention-deficit/hyperactivity disorder (ADHD) symptoms, dropouts and important side-effects, were investigated as secondary outcomes. Studies in children/adolescents and adults were analyzed separately in random-effects pairwise and network meta-analyses.
RESULTS
We analyzed data for 41 drugs and 17 dietary-supplements, from 125 RCTs (n = 7450 participants) in children/adolescents and 18 RCTs (n = 1104) in adults. The following medications could improve at least one core symptom domain in comparison with placebo: aripiprazole (k = 6 studies in analysis, SCD: SMD = 0.27 95% CI [0.09, 0.44], RB: 0.48 [0.26, 0.70]), atomoxetine (k = 3, RB:0.49 [0.18, 0.80]), bumetanide (k = 4, RB: 0.35 [0.09, 0.62], OCS: 0.61 [0.31, 0.91]), and risperidone (k = 4, SCM: 0.31 [0.06, 0.55], RB: 0.60 [0.29, 0.90]; k = 3, OCS: 1.18 [0.75, 1.61]) in children/adolescents; fluoxetine (k = 1, RB: 1.20 [0.45, 1.96]), fluvoxamine (k = 1, RB: 1.04 [0.27, 1.81]), oxytocin (k = 6, RB:0.41 [0.16, 0.66]) and risperidone (k = 1, RB: 0.97 [0.21,1.74]) in adults. There were some indications of improvement by carnosine, haloperidol, folinic acid, guanfacine, omega-3-fatty-acids, probiotics, sulforaphane, tideglusib and valproate, yet imprecise and not robust. Confidence in these estimates was very low or low, except moderate for oxytocin. Medications differed substantially in improving associated symptoms, and in their side-effect profiles.
LIMITATIONS
Most of the studies were inadequately powered (sample sizes of 20-80 participants), with short duration (8-13 weeks), and about a third focused on associated symptoms. Networks were mainly star-shaped, and there were indications of reporting bias. There was no optimal rating scale measuring change in core symptoms.
CONCLUSIONS
Some medications could improve core symptoms, although this could be likely secondary to the improvement of associated symptoms. Evidence on their efficacy and safety is preliminary; therefore, routine prescription of medications for the core symptoms cannot be recommended. Trial registration PROSPERO-ID CRD42019125317.
Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Humans; Network Meta-Analysis; Oxytocin; Risperidone
PubMed: 35246237
DOI: 10.1186/s13229-022-00488-4 -
Journal of Comparative Effectiveness... Mar 2023To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. A systematic... (Meta-Analysis)
Meta-Analysis Review
To summarize the evidence in terms of efficacy and safety of head-to-head studies of high-intensity statins regardless of the underlying population. A systematic review and meta-analysis was conducted to summarize the effect sizes in randomized controlled trials and cohort studies that compared high-intensity statins. Based on 44 articles, similar effectiveness was observed across the statins in reducing LDL levels from baseline. All statins were observed to have similar adverse drug reactions (ADRs), although higher dosages were associated with more ADRs. Based on a pooled quantitative analysis of atorvastatin 80 mg versus rosuvastatin 40 mg, rosuvastatin was statistically more effective in reducing LDL. This review further confirms that high-intensity statins reduce LDL by ≥50%, favoring rosuvastatin over atorvastatin. Additional data are needed to confirm the clinical significance on cardiovascular outcomes using real-world studies.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Atorvastatin; Cohort Studies
PubMed: 36847307
DOI: 10.57264/cer-2022-0163 -
Archives of Dermatological Research Jul 2023Treatment of actinic keratoses (AKs) can help lower the risk of eventual skin cancer and address field pre-cancerization. This review compares the different therapeutic... (Review)
Review
Treatment of actinic keratoses (AKs) can help lower the risk of eventual skin cancer and address field pre-cancerization. This review compares the different therapeutic options for actinic keratosis. Databases used include Medline, EMBASE, Web of Science and the Cochrane Library from inception to December 2019. Randomized control trials that were related to any approved or recognized treatment for actinic keratosis were included. 1186 studies were found, of which 80 with 6748 patients were included in the analysis. A network meta-analysis was not possible due to interstudy heterogeneity. The greatest degree of improvement was seen with photodynamic therapy (PDT) used adjunctively with other modalities, but this was not significantly different compared to other treatments. PDT, cryotherapy, imiquimod, ingenol mebutate (IMB), 5-fluorouracil (5-FU), trichloroacetic acid (TCA), and ablative fractional laser (AFXL), were all non-inferior to one another in terms of percent clearance of AKs, but the lowest rates of clearance were seen with diclofenac sodium. When results were substratified by body site, 5-FU, combination PDT and combination 5-FU with calcipotriol were the most beneficial for AKs on the head and neck, although they often caused the highest proportion of initial side effects. Absence of randomized control trials for surgical treatments and non-ablative laser limits comparison of these treatments to other modalities. Limitations include the lack of standardized outcome reporting limited the comparability of results across trials. The results of this analysis do not account for individual patient risk or cumulative risk for development of skin cancer. At present, PDT, cryotherapy, imiquimod, IMB, 5-FU, TCA, AFXL, and combination treatments are similarly efficacious in reducing AKs in immunocompetent patients.Registration: N/A.
Topics: Humans; Keratosis, Actinic; Imiquimod; Photochemotherapy; Treatment Outcome; Skin Neoplasms; Fluorouracil
PubMed: 36454335
DOI: 10.1007/s00403-022-02490-5 -
Asian Journal of Psychiatry Jan 2021Antipsychotics play a crucial role in the management of behavioral problems in patients undergoing hemodialysis. Oral and injectable antipsychotics are routinely... (Review)
Review
OBJECTIVE
Antipsychotics play a crucial role in the management of behavioral problems in patients undergoing hemodialysis. Oral and injectable antipsychotics are routinely prescribed to control emergent delirium or exacerbation of previous psychiatric symptoms. However scanty literature is available on the pharmacokinetics of antipsychotics in such patients. Avoiding amisulpride and warning against increasing the dosage in renal failure is the only recommendation by drug manufacturers and clinical guidelines. Hemodialysis affects the volume of distribution (V) and blood levels of antipsychotics in a complex manner. It is hence difficult to equate data on renal failure with hemodialysis to reliably predict the treatment response.
METHOD
We systematically analyzed online data from 1981 to 2019 on the use of antipsychotics in hemodialysis. The outcome was defined as the safety and efficacy of AP, measured in terms of adverse effects and relapse of existing or new onset of behavioral symptoms in Hemodialysis.
RESULTS
The data from 182 studies revealed that only 14 case reports and 1 case series met the review criteria. Oral Risperidone, Clozapine, Aripiprazole, Ziprasidone, Haloperidol, and Long-acting Risperidone, Flupenthixol, and Paliperidone were the antipsychotics studied in terms of pharmacokinetics during hemodialysis. AP levels in the blood were found to be unaffected in two studies during HD while the other two studies recommended scheduling of AP regimen w.r.t HD session. Six reports mentioned exacerbation of pre-existing psychiatric ailments in patients undergoing HD, the most common being schizophrenia.
CONCLUSION
Findings of the review reveals modest evidence favoring multiple dosing regimens of oral aripiprazole, ziprasidone, olanzapine, and risperidone. Long-acting risperidone and paliperidone are well tolerated and half of the conventional dose may be effective in the case of paliperidone. Though CYP-3A4 remains relatively and transiently unaltered during hemodialysis, none of the antipsychotics are compromised in HD. While selecting an AP during HD, one has to consider the protein binding, clearance by dialysis, duration of an HD session, route of administration of AP, and impaired bowel absorption in HD.
Topics: Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Renal Dialysis; Risperidone
PubMed: 33341539
DOI: 10.1016/j.ajp.2020.102484 -
Current Psychiatry Reports Nov 2021Over the last ten years, the treatment of psychosis has seen a near explosion of creative development in both novel agents and new delivery modalities. The current... (Review)
Review
PURPOSE OF REVIEW
Over the last ten years, the treatment of psychosis has seen a near explosion of creative development in both novel agents and new delivery modalities. The current review summarizes these developments over the past decade (2011-2020). We performed a systematic review utilizing PubMed and PsychInfo with the aim of identifying all the RCT and related analyses in adults with psychosis (schizophrenia and mania).
RECENT FINDINGS
We identified 11 significant developments: the introduction of new antipsychotics cariprazine, brexpiprazole, lumateperone, and pimavanserin; introduction of new delivery methods: subcutaneous long-acting risperidone, aripiprazole lauroxil, transdermal asenapine, and inhaled loxapine; and the introduction of new approaches such as olanzapine/samidorphan for olanzapine-associated weight gain, examination of the TAAR1 agonist SEP 363,856 as a test of concept, and the combination of Xanomeline/Trospium, an M and M muscarinic receptor agonist in conjunction with a peripheral anticholinergic. Last decade has seen a tremendous development in second-generation antipsychotics which provides unprecedented treatment options for clinicians in treating psychosis.
Topics: Adult; Antipsychotic Agents; Humans; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia
PubMed: 34843030
DOI: 10.1007/s11920-021-01298-w -
Molecular Psychiatry Feb 2022A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological... (Meta-Analysis)
Meta-Analysis
A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.
Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Carbamazepine; Female; Haloperidol; Humans; Lithium; Male; Mania; Network Meta-Analysis; Olanzapine; Paliperidone Palmitate; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Tamoxifen; Valproic Acid
PubMed: 34642461
DOI: 10.1038/s41380-021-01334-4 -
Journal of Comparative Effectiveness... Apr 2022To conduct indirect treatment comparisons between risdiplam and other approved treatments for spinal muscular atrophy (SMA). Individual patient data from risdiplam... (Review)
Review
To conduct indirect treatment comparisons between risdiplam and other approved treatments for spinal muscular atrophy (SMA). Individual patient data from risdiplam trials were compared with aggregated data from published studies of nusinersen and onasemnogene abeparvovec, accounting for heterogeneity across studies. In Type 1 SMA, studies of risdiplam and nusinersen included similar populations. Indirect comparison results found improved survival and motor function with risdiplam versus nusinersen. Comparison with onasemnogene abeparvovec in Type 1 SMA and with nusinersen in Types 2/3 SMA was challenging due to substantial differences in study populations; no concrete conclusions could be drawn from the indirect comparison analyses. Indirect comparisons support risdiplam as a superior alternative to nusinersen in Type 1 SMA.
Topics: Azo Compounds; Humans; Muscular Atrophy, Spinal; Pyrimidines; Spinal Muscular Atrophies of Childhood
PubMed: 35040693
DOI: 10.2217/cer-2021-0216 -
The Journal of Dermatological Treatment Dec 2023Mesotherapy is a technique by which lower doses of therapeutic agents and bioactive substances are administered by intradermal injections to the skin. Through... (Review)
Review
Mesotherapy is a technique by which lower doses of therapeutic agents and bioactive substances are administered by intradermal injections to the skin. Through intradermal injections, mesotherapy can increase the residence time of therapeutic agents in the affected area, thus allowing for the use of lower doses and longer intervals between sessions which may in turn improve the treatment outcome and patient compliance. This systematic review aims to summarize the current literature that evaluates the efficacy of this technique for the treatment of hair loss and provides an overview of the results observed. Of the 416 records identified, 27 articles met the inclusion criteria. To date, mesotherapy using 6 classes of agents and their combinations have been studied; this includes dutasteride, minoxidil, growth factors or autologous suspension, botulinum toxin A, stem cells, and mesh solutions/multivitamins. While several studies report statistically significant improvements in hair growth after treatment, there is currently a lack of standardized regimens. The emergence of adverse effects after mesotherapy has been reported. Further large-scale and controlled clinical trials are warranted to evaluate the utility of mesotherapy for hair loss disorders.
Topics: Humans; Mesotherapy; Alopecia; Minoxidil; Treatment Outcome; Injections, Intradermal
PubMed: 37558233
DOI: 10.1080/09546634.2023.2245084 -
Acta Neuropsychiatrica Apr 2023Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs) have evaluated the efficacy of different strategies to augment clozapine. This systematic review and meta-analysis reviewed the available RCTs that have evaluated the clinical efficacy of various pharmacological agents, non-pharmacological strategies (occupational therapy, cognitive behaviour therapy), and somatic treatment [electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation, etc.)] as augmenting agents to clozapine.
METHODS
Data were extracted using standard procedures, and risk of bias was evaluated. Effect sizes were computed for the individual studies.
RESULTS
Forty-five clinical trials were evaluated. The pooled effect size for various antipsychotic medications was 0.103 (95% CI: 0.288-0.493, < 0.001); when the effect size was evaluated for specific antipsychotics for which more than one trial was available, the effect size for risperidone was -0.27 and that for aripiprazole was 0.57. The effect size for lamotrigine was 0.145, and that for topiramate was 0.392. The effect size for ECT was 0.743 (CI: 0.094-1.392). Risk of bias was low (mean Jadad score - 3.93). Largest effect sizes were seen for mirtazapine (effect size of 5.265). Most of the studies can be considered underpowered and limited by small sample sizes.
CONCLUSIONS
To conclude, based on the findings of the present systematic review and meta-analysis, it can be said that compared to other treatment strategies, clozapine non-responsive patients respond maximum to mirtazapine followed by ECT.
Topics: Humans; Clozapine; Schizophrenia; Mirtazapine; Antipsychotic Agents; Risperidone
PubMed: 36380513
DOI: 10.1017/neu.2022.30