Effectiveness of Nutritional Therapies in Male Factor Infertility Treatment: A Systematic Review and Network Meta-analysis.

BACKGROUND: Nutritional therapies are effective alternative treatments for male infertility or subfertility. These are cost-effective and easily implementable, unlike other advanced invasive treatments. Even moderate improvements in sperm quality could improve spontaneous pregnancy. OBJECTIVE: We aimed to compare the effectiveness of all nutritional therapies in male infertility/subfertility treatment and ranked their efficacy based on type and etiology. We intend to aid clinicians with an evidence-based approach to affordable and safer initial infertility treatment for those who mainly do not wish to have other advanced invasive treatments or could not afford or have access to them. METHODS: We included 69 studies with 94 individual study arms identified from bibliographic databases and registries. We included studies in adult men with proven infertility or subfertility that investigated nutritional or dietary supplement therapies compared with control or placebo and at least reported on a sperm parameter. We undertook a network meta-analysis and performed a pairwise meta-analysis on all sperm parameter outcomes and meta-regression. No language or date restriction was imposed. A systematic article search was concluded on August 29, 2022. RESULTS: Our network meta-analysis is the first to compare all dietary interventions in a single analysis, sub-grouped by intervention type and type of infertility. L-Carnitine with micronutrients, antioxidants, and several traditional herbal supplements showed statistically and clinically significant improvement in sperm quality. Meta-regression identified that improvement in the sperm count, motility and morphology translated into increased pregnancy rates (p < 0.001; p < 0.001; p < 0.002, respectively). In particular, L-carnitine with micronutrient therapy (risk ratio [RR]: 3.60, 95% CI 1.86, 6.98, p = 0.0002), followed by zinc (RR 5.39, 95% CI 1.26, 23.04, p = 0.02), significantly improved pregnancy rates. Men with oligozoospermia (RR 4.89), followed by oligoasthenozoospermia (RR 4.20) and asthenoteratozoospermia (RR 3.53), showed a significant increase in pregnancy rates. CONCLUSION: We ranked nutritional therapies for their ability to improve sperm quality in men with infertility. Nutritional therapies, particularly L-carnitine alone or combined with micronutrients, significantly improved sperm parameters and pregnancy rates even under severe conditions. We believe these affordable solutions may be valuable for people without access to or who do not wish to undergo more invasive and costly fertility treatments.

Photodynamic therapy for skin carcinomas: A systematic review and meta-analysis.

Background: Photodynamic therapy (PDT) is increasingly used for the treatment of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). However, it is unknown whether photodynamic therapy is more effective than other commonly used treatment modalities for these cancers. Purpose: The aim of this study was to determine the relative efficacy and safety of PDT compared with placebo or other interventions for the treatment of skin carcinomas. Methods: Searches were performed in PubMed, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials databases. We included randomized controlled trials comparing the PDT with other interventions in adults skin BCC or SCC that reported on lesion response, recurrence, cosmetic appearance, or safety outcomes. Results: Seventeen unique randomized controlled trials, representing 22 study arms from 21 publications were included. The included trials included 2,166 participants, comparing methyl aminolevulinic (MAL) PDT (six studies) or aminolevulinic acid (ALA) PDT (two studies). Comparators included placebo, surgery, hexaminolevulinic (HAL) PDT, erbium: yttrium-aluminum-garnet ablative factional laser (YAG-AFL) PDT, fluorouracil, and imiquimod. There were few studies available for each comparison. Mantel-Haenszel fixed effects risk ratios were calculated for response, recurrence, cosmetic outcomes, and adverse events. MAL-PDT had similar response rates to surgery, ALA-PDT, fluorouracil and imiquimod at 3- and 12 months post-intervention. The rate of recurrence was similar, showing few differences at 12 months, but at later time points (24-60 months), fewer lesions recurred with surgery and imiquimod than with PDT. PDT also caused more adverse events and pain than other interventions. However, PDT treatment was more likely to receive a "good" or "excellent" rating for cosmetic appearance than surgery or cryotherapy. Conclusion: This systematic review and meta-analysis demonstrates that the choice of treatment modality for BCC or SCC is best chosen in the context of the location and size of the lesion, the socioeconomic circumstances of the patient, as well as the patient's preferences. We call for more high quality studies to be done, in order to enable more reliable interpretations of the data. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=368626, identifier CRD42022368626.

Chronic Fructose Substitution for Glucose or Sucrose in Food or Beverages and Metabolic Outcomes: An Updated Systematic Review and Meta-Analysis.

Despite the publication of several of meta-analyses in recent years, the effects of fructose on human health remains a topic of debate. We previously undertook two meta-analyses on post-prandial and chronic responses to isoenergetic replacement of fructose for sucrose or glucose in food or beverages (Evans et al. 2017, AJCN 106:506-518 & 519-529). Here we report on the results of an updated search with a complete re-extraction of previously identified studies and a new and more detailed subgroup-analysis and meta-regression. We identified two studies that were published after our previous analyses, which slightly altered effect sizes and conclusions. Overall, the isoenergetic substitution of fructose for glucose resulted in a statistically significant but clinically irrelevant reduction in fasting blood glucose, insulin, and triglyceride concentrations. A subgroup analysis by diabetes status revealed much larger reductions in fasting blood glucose in people with impaired glucose tolerance and type 2 diabetes. However, each of these subgroups contained only a single study. In people with a healthy body mass index, fructose consumption was associated with statistically significant, but clinically irrelevant reductions in fasting blood glucose and fasting blood insulin. Meta-regression of the outcomes by a number of pre-identified and post-hoc covariates revealed some sources of heterogeneity, such as year of publication, age of the participants at baseline, and participants' sex. However, the small number of studies and the large number of potential covariates precluded detailed investigations of effect sizes in different subpopulations. For example, well-controlled, high quality studies in people with impaired glucose tolerance and type 2 diabetes are still lacking. Taken together, the available data suggest that chronic consumption of fructose is neither more beneficial, nor more harmful than equivalent doses of sucrose or glucose for glycemic and other metabolic outcomes.

The Diagnostic Accuracy of Noninvasive Methods to Measure the Intracranial Pressure: A Systematic Review and Meta-analysis.

BACKGROUND: Although invasive monitoring is the standard method for intracranial pressure (ICP) measurement, it is not without potential for serious complications. Noninvasive methods have been proposed as alternatives to invasive ICP monitoring. The study aimed to investigate the diagnostic accuracy of the currently available noninvasive methods for intracranial hypertension (ICH) monitoring. METHODS: We searched 5 databases for articles evaluating the diagnostic accuracy of noninvasive methods in diagnosing ICH in PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase. The quantitative analysis was conducted if there were at least 2 studies evaluating a specific method. The accuracy measures included the sensitivity, specificity, likelihood ratios, and diagnostic odds ratio. RESULTS: We included 134 articles. Ultrasonographic optic nerve sheath diameter (US ONSD) had high diagnostic accuracy (estimated sensitivity of 90%; 95% confidence interval [CI], 87-92, estimated specificity of 88%; 95% CI, 84-91) while the magnetic resonance imaging (MRI) ONSD had estimated sensitivity of 77%; 95% CI, 64-87 and estimated specificity of 89%; 95% CI, 84-93, and computed tomography (CT) ONSD had estimated sensitivity of 93%; 95% CI, 90-96 and estimated specificity of 79%; 95% CI, 56-92. All MRI signs had a very high estimated specificity ranging from 90% to 99% but a low estimated sensitivity except for sinus stenosis which had high estimated sensitivity as well as specificity (90%; 95% CI, 75-96 and 96%; 95% CI, 91-99, respectively). Among the physical examination signs, pupillary dilation had a high estimated specificity (86%; 95% CI, 76-93). Other diagnostic tests to be considered included pulsatility index, papilledema, transcranial Doppler, compression or absence of basal cisterns, and ≥10 mm midline shift. Setting the cutoff value of ICH to ≥20 mm Hg instead of values <20 mm Hg was associated with higher sensitivity. Moreover, if the delay between invasive and noninvasive methods was within 1 hour, the MRI ONSD and papilledema had a significantly higher diagnostic accuracy compared to the >1 hour subgroup. CONCLUSIONS: Our study showed several promising tools for diagnosing ICH. Moreover, we demonstrated that using multiple, readily available, noninvasive methods is better than depending on a single sign such as physical examination or CT alone.

Efficacy of interpersonal psychotherapy for post-traumatic stress disorder: A systematic review and meta-analysis.

BACKGROUND: Evidence for the efficacy of treatments for post-traumatic stress disorder (PTSD) is urgently required. This systematic review and meta-analysis examines the efficacy of interpersonal psychotherapy (IPT) in reducing the symptoms of PTSD. METHODS: Five databases were searched from inception until November 2018 to identify randomized controlled trials (RCTs) that assessed the efficacy of IPT in patients with PTSD symptoms. The reference lists of included studies were also hand searched. A random effects model was used to estimate changes in a clinician-administered PTSD scale, or self-reported symptoms. RESULTS: Of 509 screened abstracts, ten clinical trials (11 study arms) involving 755 patients with PTSD symptoms were included. Nine studies (10 study arms) were included in the meta-analysis. The overall standardized mean difference was -0.44 (CI: -0.69, -0.19), p = 0.0005. This represents a change in the clinically administrated PTSD Scale (CAPS) of approximately 12 points. IPT was not superior to other active controls, such as medication and non-IPT psychotherapies, but was significantly superior to passive controls, such as waiting list and educational pamphlets. LIMITATIONS: Most studies modified the IPT protocol and did not comprehensively assess clinician fidelity to the protocol. The included studies generally had small sample sizes and were of limited quality. CONCLUSIONS: IPT may be an effective treatment for PTSD, but clinical trials with larger sample sizes and improved methodology are required to confirm effects.

Timing of Tracheostomy in Pediatric Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Tracheostomy is a very common clinical intervention in critically ill adult patients. The indications for tracheostomy procedures in pediatric patients with complex conditions have increased dramatically in recent years, but there are currently no guidelines on the optimal timing of tracheostomy in pediatric patients undergoing prolonged ventilation. DATA SOURCES: We performed a systematic search of the existing literature in MEDLINE via PubMed and Embase databases and the Cochrane Library to identify clinical trials, observational studies, and cohort studies that compare early and late tracheostomy in children. The date of the last search was August 27, 2018. Included articles were subjected to manual searching. STUDY SELECTION: Studies in mechanically ventilated children that compared early with late tracheostomy were included. DATA EXTRACTION: Data were extracted into a spreadsheet and copied into Review Manager 5.3 (The Cochrane Collaboration, Copenhagen, Denmark). DATA SYNTHESIS: Data were meta-analyzed using an inverse variance, random effects model. Continuous outcomes were calculated as mean differences with 95% CIs, and dichotomous outcomes were calculated as Mantel-Haenszel risk ratios with 95% CIs. We included eight studies (10 study arms). These studies were all retrospective cohort studies. Early tracheostomy was associated with significant reductions in mortality, days on mechanical ventilation, and length of intensive care and total hospital stay, although the lack of randomized, controlled trials limits the validity of these findings. Although variance was imputed for some studies, these conclusions did not change after removing these studies from the analysis. CONCLUSIONS: In children on mechanical ventilation, early tracheostomy may improve important medical outcomes. However, our data demonstrate the urgent need for high-quality, randomized controlled trials in the pediatric population.

Low-glycemic index diets as an intervention for diabetes: a systematic review and meta-analysis.

BACKGROUND: Low-glycemic index (GI) diets are thought to reduce postprandial glycemia, resulting in more stable blood glucose concentrations. OBJECTIVE: We hypothesized that low-GI diets would be superior to other diet types in lowering measures of blood glucose control in people with type 1 or type 2 diabetes, or impaired glucose tolerance. METHODS: We searched PubMed, the Cochrane Library, EMBASE, and clinical trials registries for published and unpublished studies up until 1 March, 2019. We included 54 randomized controlled trials in adults or children with impaired glucose tolerance, type 1 diabetes, or type 2 diabetes. Continuous data were synthesized using a random effects, inverse variance model, and presented as standardized mean differences with 95% CIs. RESULTS: Low-GI diets were effective at reducing glycated hemoglobin (HbA1c), fasting glucose, BMI, total cholesterol, and LDL, but had no effect on fasting insulin, HOMA-IR, HDL, triglycerides, or insulin requirements. The reduction in fasting glucose and HbA1c was inversely correlated with body weight. The greatest reduction in fasting blood glucose was seen in the studies of the longest duration. CONCLUSIONS: Low-GI diets may be useful for glycemic control and may reduce body weight in people with prediabetes or diabetes.

Chronic fructose substitution for glucose or sucrose in food or beverages has little effect on fasting blood glucose, insulin, or triglycerides: a systematic review and meta-analysis.

Background: Conflicting evidence exists on the role of long-term fructose consumption on health. No systematic review has addressed the effect of isoenergetic fructose replacement of other sugars and its effect on glycated hemoglobin (HbA1c), fasting blood glucose, insulin, and triglycerides.Objective: The objective of this study was to review the evidence for a reduction in fasting glycemic and insulinemic markers after chronic, isoenergetic replacement of glucose or sucrose in foods or beverages by fructose. The target populations were persons without diabetes, those with impaired glucose tolerance, and those with type 2 diabetes.Design: We searched the Cochrane Library, MEDLINE, EMBASE, the WHO International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov The date of the last search was 26 April 2016. We included randomized controlled trials of isoenergetic replacement of glucose, sucrose, or both by fructose in adults or children with or without diabetes of ≥2 wk duration that measured fasting blood glucose. The main outcomes analyzed were fasting blood glucose and insulin as well as fasting triglycerides, blood lipoproteins, HbA1c, and body weight.Results: We included 14 comparison arms from 11 trials, including 277 patients. The studies varied in length from 2 to 10 wk (mean: 28 d) and included doses of fructose between 40 and 150 g/d (mean: 68 g/d). Fructose substitution in some subgroups resulted in significantly but only slightly lowered fasting blood glucose (-0.14 mmol/L; 95% CI: -0.24, -0.036 mmol/L), HbA1c [-10 g/L (95% CI: -12.90, -7.10 g/L; impaired glucose tolerance) and -6 g/L (95% CI: -8.47, -3.53 g/L; normoglycemia)], triglycerides (-0.08 mmol/L; 95% CI: -0.14, -0.02 mmol/L), and body weight (-1.40 kg; 95% CI: -2.07, -0.74 kg). There was no effect on fasting blood insulin or blood lipids.Conclusions: The evidence suggests that the substitution of fructose for glucose or sucrose in food or beverages may be of benefit to individuals, particularly those with impaired glucose tolerance or type 2 diabetes. However, additional high-quality studies in these populations are required.

Fructose replacement of glucose or sucrose in food or beverages lowers postprandial glucose and insulin without raising triglycerides: a systematic review and meta-analysis.

Background: Conflicting evidence exists on the effects of fructose consumption in people with type 1 and type 2 diabetes mellitus. No systematic review has addressed the effect of isoenergetic fructose replacement of glucose or sucrose on peak postprandial glucose, insulin, and triglyceride concentrations.Objective: The objective of this study was to review the evidence for postprandial glycemic and insulinemic responses after isoenergetic replacement of either glucose or sucrose in foods or beverages with fructose.Design: We searched the Cochrane Library, MEDLINE, EMBASE, the WHO International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov The date of the last search was 26 April 2016. We included randomized controlled trials measuring peak postprandial glycemia after isoenergetic replacement of glucose, sucrose, or both with fructose in healthy adults or children with or without diabetes. The main outcomes analyzed were peak postprandial blood glucose, insulin, and triglyceride concentrations.Results: Replacement of either glucose or sucrose by fructose resulted in significantly lowered peak postprandial blood glucose, particularly in people with prediabetes and type 1 and type 2 diabetes. Similar results were obtained for insulin. Peak postprandial blood triglyceride concentrations did not significantly increase.Conclusions: Strong evidence exists that substituting fructose for glucose or sucrose in food or beverages lowers peak postprandial blood glucose and insulin concentrations. Isoenergetic replacement does not result in a substantial increase in blood triglyceride concentrations.

Truncation of merozoite surface protein 3 disrupts its trafficking and that of acidic-basic repeat protein to the surface of Plasmodium falciparum merozoites.

Merozoite surface protein 3 (MSP3), an important vaccine candidate, is a soluble polymorphic antigen associated with the surface of Plasmodium falciparum merozoites. The MSP3 sequence contains three blocks of heptad repeats that are consistent with the formation of an intramolecular coiled-coil. MSP3 also contains a glutamic acid-rich region and a putative leucine zipper sequence at the C-terminus. We have disrupted the msp3 gene by homologous recombination, resulting in the expression of a truncated form of MSP3 that lacks the putative leucine zipper sequence but retains the glutamic acid-rich region and the heptad repeats. Here, we show that truncated MSP3, lacking the putative leucine zipper region, does not localize to the parasitophorous vacuole or interact with the merozoite surface. Furthermore, the acidic-basic repeat antigen (ABRA), which is present on the merozoite surface, also was not localized to the merozoite surface in parasites expressing the truncated form of MSP3. The P. falciparum merozoites lacking MSP3 and ABRA on the surface show reduced invasion into erythrocytes. These results suggest that MSP3 is not absolutely essential for blood stage growth and that the putative leucine zipper region is required for the trafficking of both MSP3 and ABRA to the parasitophorous vacuole.

Functional analysis of Plasmodium falciparum merozoite antigens: implications for erythrocyte invasion and vaccine development.

Malaria is a major human health problem and is responsible for over 2 million deaths per year. It is caused by a number of species of the genus Plasmodium, and Plasmodium falciparum is the causative agent of the most lethal form. Consequently, the development of a vaccine against this parasite is a priority. There are a number of stages of the parasite life cycle that are being targeted for the development of vaccines. Important candidate antigens include proteins on the surface of the asexual merozoite stage, the form that invades the host erythrocyte. The development of methods to manipulate the genome of Plasmodium species has enabled the construction of gain-of-function and loss-of-function mutants and provided new strategies to analyse the role of parasite proteins. This has provided new information on the role of merozoite antigens in erythrocyte invasion and also allows new approaches to address their potential as vaccine candidates.