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International Journal of Environmental... Apr 2020Creatine monohydrate is a nutritional supplement often consumed by athletes in anaerobic sports. Creatine is naturally found in most meat products; therefore,...
BACKGROUND
Creatine monohydrate is a nutritional supplement often consumed by athletes in anaerobic sports. Creatine is naturally found in most meat products; therefore, vegetarians have reduced creatine stores and may benefit from supplementation.
OBJECTIVE
to determine the effects of creatine supplementation on vegetarians.
DATA SOURCES
PubMed and SPORTDiscus. Eligibility criteria: Randomized controlled trials (parallel group, cross-over studies) or prospective studies.
PARTICIPANTS
Vegetarians.
INTERVENTION
Creatine supplementation. Study appraisal and synthesis: A total of 64 records were identified, and eleven full-text articles (covering nine studies) were included in this systematic review.
RESULTS
Creatine supplementation in vegetarians increased total creatine, creatine, and phosphocreatine concentrations in vastus lateralis and gastrocnemius muscle, plasma, and red blood cells, often to levels greater than omnivores. Creatine supplementation had no effect on brain levels of phosphocreatine. Creatine supplementation increased lean tissue mass, type II fiber area, insulin-like growth factor-1, muscular strength, muscular endurance, Wingate mean power output, and brain function (memory and intelligence) in vegetarian participants. Studies were mixed on whether creatine supplementation improved exercise performance in vegetarians to a greater extent compared to omnivores.
LIMITATIONS
Studies that were reviewed had moderate-high risk of bias.
CONCLUSIONS
Overall, it appears vegetarian athletes are likely to benefit from creatine supplementation.
Topics: Athletes; Cognition; Creatine; Diet, Vegetarian; Dietary Supplements; Humans; Memory; Physical Fitness; Prospective Studies; Vegetarians
PubMed: 32349356
DOI: 10.3390/ijerph17093041 -
International Breastfeeding Journal Sep 2022Despite extensive benefits and high intentions, few mothers breastfeed exclusively for the recommended duration. Maternal mental health is an important underlying factor... (Review)
Review
BACKGROUND
Despite extensive benefits and high intentions, few mothers breastfeed exclusively for the recommended duration. Maternal mental health is an important underlying factor associated with barriers and reduced rates of breastfeeding intent, initiation, and continuation. Given evidence of a bidirectional association between maternal mental health and breastfeeding, it is important to consider both factors when examining the efficacy of interventions to improve these outcomes. The purpose of this manuscript is to review the literature on the efficacy of behavioral interventions focused on both maternal mental health and breastfeeding outcomes, examining the intersection of the two.
METHODS
This systematic review was completed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Studies were selected if they were available in English, used primary experimental design, and used a behavioral intervention type to examine maternal mental health and breastfeeding outcomes. Articles were identified from PubMed, CINAHL, Embase, and PsycINFO from database inception to 3 March 2022. Study quality was assessed using the Cochrane Risk of Bias tool. Results were synthesized by intervention success for 1. Mental health and breastfeeding, 2. Breastfeeding only, 3. Mental health only, and 4. No intervention effect. PROSPERO CRD42021224228.
RESULTS
Thirty interventions reported in 33 articles were identified, representing 15 countries. Twelve studies reported statistically significant positive effect of the intervention on both maternal mental health and breastfeeding; most showing a decrease in self-report depressive and/or anxiety symptoms in parallel to an increase in breastfeeding duration and/or exclusivity. Common characteristics of successful interventions were a) occurring across pregnancy and postpartum, b) delivered by hospital staff or multidisciplinary teams, c) offered individually, and d) designed to focus on breastfeeding and maternal mental health or on breastfeeding only. Our results are not representative of all countries, persons, experiences, circumstances, or physiological characteristics.
CONCLUSIONS
Interventions that extend the perinatal period and offer individualized support from both professionals and peers who collaborate through a continuum of settings (e.g., health system, home, and community) are most successful in improving both mental health and breastfeeding outcomes. The benefits of improving these outcomes warrant continued development and implementation of such interventions.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021224228.
Topics: Behavior Therapy; Breast Feeding; Female; Humans; Mental Health; Mothers; Postpartum Period; Pregnancy
PubMed: 36064573
DOI: 10.1186/s13006-022-00501-9 -
The Cochrane Database of Systematic... Mar 2023Spinal cord stimulation (SCS) is a surgical intervention used to treat persistent low back pain. SCS is thought to modulate pain by sending electrical signals via... (Review)
Review
BACKGROUND
Spinal cord stimulation (SCS) is a surgical intervention used to treat persistent low back pain. SCS is thought to modulate pain by sending electrical signals via implanted electrodes into the spinal cord. The long term benefits and harms of SCS for people with low back pain are uncertain.
OBJECTIVES
To assess the effects, including benefits and harms, of SCS for people with low back pain.
SEARCH METHODS
On 10 June 2022, we searched CENTRAL, MEDLINE, Embase, and one other database for published trials. We also searched three clinical trials registers for ongoing trials.
SELECTION CRITERIA
We included all randomised controlled trials and cross-over trials comparing SCS with placebo or no treatment for low back pain. The primary comparison was SCS versus placebo, at the longest time point measured in the trials. Major outcomes were mean low back pain intensity, function, health-related quality of life, global assessment of efficacy, withdrawals due to adverse events, adverse events, and serious adverse events. Our primary time point was long-term follow-up (≥ 12 months).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 13 studies with 699 participants: 55% of participants were female; mean age ranged from 47 to 59 years; and all participants had chronic low back pain with mean duration of symptoms ranging from five to 12 years. Ten cross-over trials compared SCS with placebo. Three parallel-group trials assessed the addition of SCS to medical management. Most studies were at risk of performance and detection bias from inadequate blinding and selective reporting bias. The placebo-controlled trials had other important biases, including lack of accounting for period and carryover effects. Two of the three parallel trials assessing SCS as an addition to medical management were at risk of attrition bias, and all three had substantial cross-over to the SCS group for time points beyond six months. In the parallel-group trials, we considered the lack of placebo control to be an important source of bias. None of our included studies evaluated the impact of SCS on mean low back pain intensity in the long term (≥ 12 months). The studies most often assessed outcomes in the immediate term (less than one month). At six months, the only available evidence was from a single cross-over trial (50 participants). There was moderate-certainty evidence that SCS probably does not improve back or leg pain, function, or quality of life compared with placebo. Pain was 61 points (on a 0- to 100-point scale, 0 = no pain) at six months with placebo, and 4 points better (8.2 points better to 0.2 points worse) with SCS. Function was 35.4 points (on a 0- to 100-point scale, 0 = no disability or best function) at six months with placebo, and 1.3 points better (3.9 points better to 1.3 points worse) with SCS. Health-related quality of life was 0.44 points out of 1 (0 to 1 index, 0 = worst quality of life) at six months with placebo, and 0.04 points better (0.16 points better to 0.08 points worse) with SCS. In that same study, nine participants (18%) experienced adverse events and four (8%) required revision surgery. Serious adverse events with SCS included infections, neurological damage, and lead migration requiring repeated surgery. We could not provide effect estimates of the relative risks as events were not reported for the placebo period. In parallel trials assessing SCS as an addition to medical management, it is uncertain whether, in the medium or long term, SCS can reduce low back pain, leg pain, or health-related quality of life, or if it increases the number of people reporting a 50% improvement or better, because the certainty of the evidence was very low. Low-certainty evidence suggests that adding SCS to medical management may slightly improve function and slightly reduce opioid use. In the medium term, mean function (0- to 100-point scale; lower is better) was 16.2 points better with the addition of SCS to medical management compared with medical management alone (95% confidence interval (CI) 19.4 points better to 13.0 points better; I = 95%; 3 studies, 430 participants; low-certainty evidence). The number of participants reporting opioid medicine use was 15% lower with the addition of SCS to medical management (95% CI 27% lower to 0% lower; I = 0%; 2 studies, 290 participants; low-certainty evidence). Adverse events with SCS were poorly reported but included infection and lead migration. One study found that, at 24 months, 13 of 42 people (31%) receiving SCS required revision surgery. It is uncertain to what extent the addition of SCS to medical management increases the risk of withdrawals due to adverse events, adverse events, or serious adverse events, because the certainty of the evidence was very low.
AUTHORS' CONCLUSIONS
Data in this review do not support the use of SCS to manage low back pain outside a clinical trial. Current evidence suggests SCS probably does not have sustained clinical benefits that would outweigh the costs and risks of this surgical intervention.
Topics: Female; Humans; Male; Middle Aged; Analgesics, Opioid; Low Back Pain; Quality of Life; Spinal Cord Stimulation
PubMed: 36878313
DOI: 10.1002/14651858.CD014789.pub2 -
Frontiers in Psychiatry 2021Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce...
Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies ( = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.
PubMed: 34566723
DOI: 10.3389/fpsyt.2021.724606 -
Scandinavian Journal of Medicine &... Jan 2022Short-term energy deficits impair anabolic hormones and muscle protein synthesis. However, the effects of prolonged energy deficits on resistance training (RT) outcomes... (Meta-Analysis)
Meta-Analysis
Short-term energy deficits impair anabolic hormones and muscle protein synthesis. However, the effects of prolonged energy deficits on resistance training (RT) outcomes remain unexplored. Thus, we conducted a systematic review of PubMed and SportDiscus for randomized controlled trials performing RT in an energy deficit (RT+ED) for ≥3 weeks. We first divided the literature into studies with a parallel control group without an energy deficit (RT+CON; Analysis A) and studies without RT+CON (Analysis B). Analysis A consisted of a meta-analysis comparing gains in lean mass (LM) and strength between RT+ED and RT+CON. Studies in Analysis B were matched with separate RT+CON studies for participant and intervention characteristics, and we qualitatively compared the gains in LM and strength between RT+ED and RT+CON. Finally, Analyses A and B were pooled into a meta-regression examining the relationship between the magnitude of the energy deficit and LM. Analysis A showed LM gains were impaired in RT+ED vs RT+CON (effect size (ES) = -0.57, p = 0.02), but strength gains were comparable between conditions (ES = -0.31, p = 0.28). Analysis B supports the impairment of LM in RT+ED (ES: -0.11, p = 0.03) vs RT+CON (ES: 0.20, p < 0.001) but not strength (RT+ED ES: 0.84; RT+CON ES: 0.81). Finally, our meta-regression demonstrated that an energy deficit of ~500 kcal · day prevented gains in LM. Individuals performing RT to build LM should avoid prolonged energy deficiency, and individuals performing RT to preserve LM during weight loss should avoid energy deficits >500 kcal day .
Topics: Humans; Muscle Strength; Muscle, Skeletal; Resistance Training; Weight Loss
PubMed: 34623696
DOI: 10.1111/sms.14075 -
European Journal of Internal Medicine Oct 2022Portal vein thrombosis (PVT) may be associated with negative outcomes in patients with liver cirrhosis. However, the prevalence and incidence of PVT in liver cirrhosis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Portal vein thrombosis (PVT) may be associated with negative outcomes in patients with liver cirrhosis. However, the prevalence and incidence of PVT in liver cirrhosis are heterogeneous among studies and have not been sufficiently determined yet.
METHODS
The PubMed, EMBASE, and Cochrane Library databases were searched. Eligible studies would explore the prevalence and/or incidence of PVT in liver cirrhosis without hepatocellular carcinoma or abdominal surgery. Pooled proportion with 95% confidence interval (CI) was calculated using a random-effect model. Factors associated with the presence/occurrence of PVT were also extracted.
RESULTS
Among the 8549 papers initially identified, 74 were included. Fifty-four studies explored the prevalence of PVT in liver cirrhosis with a pooled prevalence of 13.92% (95%CI=11.18-16.91%). Based on cross-sectional data, Child-Pugh class B/C, higher D-dimer, ascites, and use of non-selective beta-blockers (NSBBs) were associated with the presence of PVT in liver cirrhosis. Twenty-three studies explored the incidence of PVT in liver cirrhosis with a pooled incidence of 10.42% (95%CI=8.16-12.92%). Based on cohort data, Child-Pugh class B/C, higher model of end-stage liver disease score, higher D-dimer, lower platelets count, decreased portal flow velocity, ascites, use of NSBBs, and moderate or high-risk esophageal varices could predict the occurrence of PVT in liver cirrhosis.
CONCLUSION
Approximately one seventh of cirrhotic patients have PVT, and one tenth will develop PVT. Progression of liver cirrhosis and portal hypertension seems to be in parallel with the risk of PVT. Prospective studies with detailed information about classification and extension of PVT in liver cirrhosis are needed.
Topics: Adrenergic beta-Antagonists; Ascites; Cross-Sectional Studies; Humans; Liver Cirrhosis; Portal Vein; Prospective Studies; Venous Thrombosis
PubMed: 35688747
DOI: 10.1016/j.ejim.2022.05.032 -
BMC Psychiatry Nov 2019Over the past decade, smartphone use has become widespread amongst today's children and young people (CYP) which parallels increases in poor mental health in this group.... (Meta-Analysis)
Meta-Analysis
Prevalence of problematic smartphone usage and associated mental health outcomes amongst children and young people: a systematic review, meta-analysis and GRADE of the evidence.
BACKGROUND
Over the past decade, smartphone use has become widespread amongst today's children and young people (CYP) which parallels increases in poor mental health in this group. Simultaneously, media concern abounds about the existence of 'smartphone addiction' or problematic smartphone use. There has been much recent research concerning the prevalence of problematic smartphone use is in children and young people who use smartphones, and how this syndrome relates to mental health outcomes, but this has not been synthesized and critically evaluated.
AIMS
To conduct a systematic review and meta-analysis to examine the prevalence of PSU and quantify the association with mental health harms.
METHODS
A search strategy using Medical Subject Headings was developed and adapted for eight databases between January 1, 1st 2011 to October 15th 2017. No language restriction was applied. Of 924 studies identified, 41 were included in this review, three of which were cohort studies and 38 were cross sectional studies. The mental health outcomes were self-reported: depression; anxiety; stress; poor sleep quality; and decreased educational attainment, which were synthesized according to an a priori protocol.
RESULTS
The studies included 41,871 CYP, and 55% were female. The median prevalence of PSU amongst CYP was 23.3% (14.0-31.2%). PSU was associated with an increased odds of depression (OR = 3.17;95%CI 2.30-4.37;I = 78%); increased anxiety (OR = 3.05 95%CI 2.64-3.53;I = 0%); higher perceived stress (OR = 1.86;95%CI 1.24-2.77;I = 65%); and poorer sleep quality (OR = 2.60; 95%CI; 1.39-4.85, I = 78%).
CONCLUSIONS
PSU was reported in approximately one in every four CYP and accompanied by an increased odds of poorer mental health. PSU is an evolving public health concern that requires greater study to determine the boundary between helpful and harmful technology use. Policy guidance is needed to outline harm reduction strategies.
Topics: Adolescent; Anxiety; Behavior, Addictive; Child; Depression; Educational Status; Female; Humans; Male; Mental Health; Odds Ratio; Prevalence; Self Report; Sleep Wake Disorders; Smartphone; Stress, Psychological; Young Adult
PubMed: 31779637
DOI: 10.1186/s12888-019-2350-x -
The Cochrane Database of Systematic... Jun 2022Acute respiratory distress syndrome (ARDS) is a significant cause of hospitalisation and death in young children. Positioning and mechanical ventilation have been... (Review)
Review
BACKGROUND
Acute respiratory distress syndrome (ARDS) is a significant cause of hospitalisation and death in young children. Positioning and mechanical ventilation have been regularly used to reduce respiratory distress and improve oxygenation in hospitalised patients. Due to the association of prone positioning (lying on the abdomen) with sudden infant death syndrome (SIDS) within the first six months, it is recommended that young infants be placed on their back (supine). However, prone positioning may be a non-invasive way of increasing oxygenation in individuals with acute respiratory distress, and offers a more significant survival advantage in those who are mechanically ventilated. There are substantial differences in respiratory mechanics between adults and infants. While the respiratory tract undergoes significant development within the first two years of life, differences in airway physiology between adults and children become less prominent by six to eight years old. However, there is a reduced risk of SIDS during artificial ventilation in hospitalised infants. Thus, an updated review focusing on positioning for infants and young children with ARDS is warranted. This is an update of a review published in 2005, 2009, and 2012.
OBJECTIVES
To compare the effects of different body positions in hospitalised infants and children with acute respiratory distress syndrome aged between four weeks and 16 years.
SEARCH METHODS
We searched CENTRAL, which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE, Embase, and CINAHL from January 2004 to July 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs comparing two or more positions for the management of infants and children hospitalised with ARDS.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from each study. We resolved differences by consensus, or referred to a third contributor to arbitrate. We analysed bivariate outcomes using an odds ratio (OR) and 95% confidence interval (CI). We analysed continuous outcomes using a mean difference (MD) and 95% CI. We used a fixed-effect model, unless heterogeneity was significant (I statistic > 50%), when we used a random-effects model.
MAIN RESULTS
We included six trials: four cross-over trials, and two parallel randomised trials, with 198 participants aged between 4 weeks and 16 years, all but 15 of whom were mechanically ventilated. Four trials compared prone to supine positions. One trial compared the prone position to good-lung dependent (where the person lies on the side of the healthy lung, e.g. if the right lung was healthy, they were made to lie on the right side), and independent (or non-good-lung independent, where the person lies on the opposite side to the healthy lung, e.g. if the right lung was healthy, they were made to lie on the left side) position. One trial compared good-lung independent to good-lung dependent positions. When the prone (with ventilators) and supine positions were compared, there was no information on episodes of apnoea or mortality due to respiratory events. There was no conclusive result in oxygen saturation (SaO MD 0.40 mmHg, 95% CI -1.22 to 2.66; 1 trial, 30 participants; very low certainty evidence); blood gases, PCO (MD 3.0 mmHg, 95% CI -1.93 to 7.93; 1 trial, 99 participants; low certainty evidence), or PO (MD 2 mmHg, 95% CI -5.29 to 9.29; 1 trial, 99 participants; low certainty evidence); or lung function (PaO/FiO ratio; MD 28.16 mmHg, 95% CI -9.92 to 66.24; 2 trials, 121 participants; very low certainty evidence). However, there was an improvement in oxygenation index (FiO% X M/ PaO) with prone positioning in both the parallel trials (MD -2.42, 95% CI -3.60 to -1.25; 2 trials, 121 participants; very low certainty evidence), and the cross-over study (MD -8.13, 95% CI -15.01 to -1.25; 1 study, 20 participants). Derived indices of respiratory mechanics, such as tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP) were reported. There was an apparent decrease in tidal volume between prone and supine groups in a parallel study (MD -0.60, 95% CI -1.05 to -0.15; 1 study, 84 participants; very low certainty evidence). When prone and supine positions were compared in a cross-over study, there were no conclusive results in respiratory compliance (MD 0.07, 95% CI -0.10 to 0.24; 1 study, 10 participants); changes in PEEP (MD -0.70 cm HO, 95% CI -2.72 to 1.32; 1 study, 10 participants); or resistance (MD -0.00, 95% CI -0.05 to 0.04; 1 study, 10 participants). One study reported adverse events. There were no conclusive results for potential harm between groups in extubation (OR 0.57, 95% CI 0.13 to 2.54; 1 trial, 102 participants; very low certainty evidence); obstructions of the endotracheal tube (OR 5.20, 95% CI 0.24 to 111.09; 1 trial, 102 participants; very low certainty evidence); pressure ulcers (OR 1.00, 95% CI 0.41 to 2.44; 1 trial, 102 participants; very low certainty evidence); and hypercapnia (high levels of arterial carbon dioxide; OR 3.06, 95% CI 0.12 to 76.88; 1 trial, 102 participants; very low certainty evidence). One study (50 participants) compared supine positions to good-lung dependent and independent positions. There was no conclusive evidence that PaO was different between supine and good-lung dependent positioning (MD 3.44 mm Hg, 95% CI -23.12 to 30.00; 1 trial, 25 participants; very low certainty evidence). There was also no conclusive evidence for supine position and good-lung independent positioning (MD -2.78 mmHg, 95% CI -28.84, 23.28; 25 participants; very low certainty evidence); or between good-lung dependent and independent positioning (MD 6.22, 95% CI -21.25 to 33.69; 1 trial, 25 participants; very low certainty evidence). As most trials did not describe how possible biases were addressed, the potential for bias in these findings is unclear.
AUTHORS' CONCLUSIONS
Although included studies suggest that prone positioning may offer some advantage, there was little evidence to make definitive recommendations. There appears to be low certainty evidence that positioning improves oxygenation in mechanically ventilated children with ARDS. Due to the increased risk of SIDS with prone positioning and lung injury with artificial ventilation, it is recommended that hospitalised infants and children should only be placed in this position while under continuous cardiorespiratory monitoring.
Topics: Adult; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Patient Positioning; Positive-Pressure Respiration; Respiration, Artificial; Respiratory Distress Syndrome; Sudden Infant Death
PubMed: 35661343
DOI: 10.1002/14651858.CD003645.pub4 -
Clinical Neurology and Neurosurgery Jul 2020We conducted an updated systematic review on the safety and efficacy of amantadine in cognitive recovery after traumatic brain injury (TBI), in order to determine if the...
We conducted an updated systematic review on the safety and efficacy of amantadine in cognitive recovery after traumatic brain injury (TBI), in order to determine if the current literature justifies its use in this clinical condition. A comprehensive search strategy was applied to three databases (PubMed, Scopus, and Cochrane). Only randomized clinical trials (RCTs) that compared the effect of amantadine and placebo in adults within 3 months of TBI were included in the review. Study characteristics, outcomes, and methodological quality were synthesized. This systematic review was conducted and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A quantitative synthesis (meta-analysis) was not feasible due to the large heterogeneity of studies identified. Three parallel RCTs and one cross-over RCT, with a total of 325 patients were included. All of the studies evaluated only severe TBI in adults. Amantadine was found to be well tolerated across the studies. Two RCTs reported improvement in the intermediate-term cognitive recovery (four to six weeks after end of treatment), using DRS (in both studies) and MMSE, GOS, and FIM-Cog (in one study). The effect of amantadine on the short-term (seven days to discharge) and long-term (six months from the injury) cognitive outcome was found not superior to placebo in two RCTs. The rate of severe adverse events was found to be consistently very low across the studies (the incidence of seizures, elevation in liver enzymes and cardiac death was 0.7 %, 1.9 %, and 0.3 %, respectively). In conclusion, amantadine seems to be well tolerated and might hasten the rate of cognitive recovery in the intermediate-term outcome. However, the long-term effect of amantadine in cognitive recovery is not well defined and further large randomized clinical trials in refined subgroups of patients are needed to better define its application.
Topics: Amantadine; Brain Injuries, Traumatic; Cognition Disorders; Humans; Nootropic Agents; Randomized Controlled Trials as Topic; Recovery of Function
PubMed: 32244036
DOI: 10.1016/j.clineuro.2020.105815 -
Human Reproduction Update Feb 2021Mild ovarian stimulation has emerged as an alternative to conventional IVF with the advantages of being more patient-friendly and less expensive. Inadequate data on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mild ovarian stimulation has emerged as an alternative to conventional IVF with the advantages of being more patient-friendly and less expensive. Inadequate data on pregnancy outcomes and concerns about the cycle cancellation rate (CCR) have prevented mild, or low-dose, IVF from gaining wide acceptance.
OBJECTIVE AND RATIONALE
To evaluate parallel-group randomised controlled trials (RCTs) on IVF where comparisons were made between a mild (≤150 IU daily dose) and conventional stimulation in terms of clinical outcomes and cost-effectiveness in patients described as poor, normal and non-polycystic ovary syndrome (PCOS) hyper-responders to IVF.
SEARCH METHODS
Searches with no language restrictions were performed using Medline, Embase, Cochrane central, Pre-Medicine from January 1990 until April 2020, using pre-specified search terms. References of included studies were hand-searched as well as advance access articles to key journals. Only parallel-group RCTs that used ≤150 IU daily dose of gonadotrophin as mild-dose IVF (MD-IVF) and compared with a higher conventional dose (CD-IVF) were included. Studies were grouped under poor, normal or hyper-responders as described by the authors in their inclusion criteria. Women with PCOS were excluded in the hyper-responder group. The risk of bias was assessed as per Cochrane Handbook for the included studies. The quality of evidence (QoE) was assessed according to the GRADE system. PRISMA guidance was followed for review methodology.
OUTCOMES
A total of 31 RCTs were included in the analysis: 15 in the poor, 14 in the normal and 2 in the hyper-responder group. Live birth rates (LBRs) per randomisation were similar following use of MD-IVF in poor (relative risk (RR) 0.91 (CI 0.68, 1.22)), normal (RR 0.88 (CI 0.69, 1.12)) and hyper-responders (RR 0.98 (CI 0.79, 1.22)) when compared to CD-IVF. QoE was moderate. Cumulative LBRs (5 RCTs, n = 2037) also were similar in all three patient types (RR 0.96 (CI 0.86 1.07) (moderate QoE). Risk of ovarian hyperstimulation syndrome was significantly less with MD-IVF than CD-IVF in both normal (RR 0.22 (CI 0.10, 0.50)) and hyper-responders (RR 0.47 (CI 0.31, 0.72)), with moderate QoE. The CCRs were comparable in poor (RR 1.33 (CI 0.96, 1.85)) and hyper-responders (RR 1.31 (CI 0.98, 1.77)) but increased with MD-IVF among normal responders (RR 2.08 (CI 1.38, 3.14)); all low to very low QoE. Although fewer oocytes were retrieved and fewer embryos created with MD-IVF, the proportion of high-grade embryos was similar in all three population types (low QoE). Compared to CD-IVF, MD-IVF was associated with less gonadotrophin use and lower cost.
WIDER IMPLICATIONS
This updated review provides reassurance on using MD-IVF not only for the LBR per cycle but also for the cumulative LBR, with moderate QoE. With risks identified with 'freeze-all' strategies, it may be time to recommend mild-dose ovarian stimulation for IVF for all categories of women i.e. hyper, poor and normal responders to IVF.
Topics: Female; Fertilization in Vitro; Humans; Live Birth; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Sperm Injections, Intracytoplasmic
PubMed: 33146690
DOI: 10.1093/humupd/dmaa035