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Nutrients Jul 2020Neuropathic pain describes a range of unpleasant sensations caused by a lesion or disease of the somatosensory nervous system. The sensations caused by neuropathic pain...
Neuropathic pain describes a range of unpleasant sensations caused by a lesion or disease of the somatosensory nervous system. The sensations caused by neuropathic pain are debilitating and improved treatment regimens are sought in order to improve the quality of life of patients. One proposed treatment for neuropathic pain is vitamin B12, which is thought to alleviate pain by a number of mechanisms including promoting myelination, increasing nerve regeneration and decreasing ectopic nerve firing. In this paper, the evidence for B12 as a drug treatment for neuropathic pain is reviewed. Twenty four published articles were eligible for inclusion in this systematic review in which a range of treatment regimens were evaluated including both B12 monotherapy and B12 in combination with other vitamins or conventional treatments, such as gabapentinoids. Overall, this systematic review demonstrates that there is currently some evidence for the therapeutic effect of B12 in the treatment of post-herpetic neuralgia (level II evidence) and the treatment of painful peripheral neuropathy (level III evidence).
Topics: Clinical Trials as Topic; Humans; Neuralgia; Observational Studies as Topic; Peripheral Nervous System Diseases; Treatment Outcome; Vitamin B 12
PubMed: 32722436
DOI: 10.3390/nu12082221 -
Journal of Cosmetic Dermatology Dec 2022Tofacitinib, a potent JAK inhibitor, has gained increasing interest, in recent years, among dermatologists for the management of refractory alopecia areata. Despite a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tofacitinib, a potent JAK inhibitor, has gained increasing interest, in recent years, among dermatologists for the management of refractory alopecia areata. Despite a growing number of studies on its safety and efficacy, there is still a lack of clarity, especially in the pediatric population, in treatment considerations such as proper dosage, treatment duration, side-effect profile, and therapeutic strategies to guide clinicians.
METHODS
Multiple databases were systematically searched. Following the PRISMA diagram, of a pool of 601 papers, seven met a checklist of inclusion criteria. These were observational studies including a total of 59 patients from four to 19 years of age.
RESULTS
In the evaluated studies, tofacitinib was administered either orally at a 2.5 to 15 mg daily (mostly 5 mg twice a day) dosage for 2 to 38 months or in the form of a 2% topical solution for 3-17 months. Metanalysis showed that 49% (95% CI: 29%-69%, I = 59.94%) of patients experienced a reversal of alopecia after a minimum of 3 to 9 months of therapy. Fifty-five percent (95% CI: 23%-86%, I = 75.07%) and 41% (95% CI: 23%-59%, I = 0.00%) showed Good/complete and partial response rates, respectively. Oral administration was significantly more efficacious than topical application (73% vs 23%, p-Value = 0.04). Few side effects such as diarrhea and mild liver transaminases abnormalities were noted in several patients.
CONCLUSION
Results of this review suggest that tofacitinib at 2.5-15 mg daily (especially 5 mg twice daily) oral formulation or 2% topical solution can be regarded as a viable alternative or adjunct to the conventional treatment options for moderate to severe forms of alopecia areata in children owing to its acceptable efficacy and side-effect profile. However, uncertainties continue to exist around treatment strategies including initial and maintenance dosages, route of administration, dose adjustments, the timing of tapering or discontinuation, and associated treatment modalities.
Topics: Humans; Child; Alopecia Areata; Pyrroles; Piperidines
PubMed: 36177815
DOI: 10.1111/jocd.15425 -
Obesity Surgery Nov 2020Bariatric surgery may increase the risk of iron, vitamin B, folate and copper deficiencies, which can cause anaemia. This review aims to critique the evidence on the... (Review)
Review
Bariatric surgery may increase the risk of iron, vitamin B, folate and copper deficiencies, which can cause anaemia. This review aims to critique the evidence on the prevalence of these nutritional deficiencies and the impact on anaemia in the first 12 months after surgery. PRISMA and MOOSE frameworks, the NHMRC evidence hierarchy and The Academy of Nutrition and Dietetics bias tool were used to systematically critique current literature. Seventeen studies reported on deficiency prevalence with the majority being of low quality. Important confounders to serum micronutrient levels were not adequately considered. Results on the prevalence of nutritional anaemias were also lacking. Further investigation into the prevalence of iron, vitamin B, folate and copper deficiency and its impact on anaemia in bariatric surgery is needed.
Topics: Anemia; Bariatric Surgery; Copper; Folic Acid; Gastric Bypass; Humans; Iron; Obesity, Morbid; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins
PubMed: 32785814
DOI: 10.1007/s11695-020-04872-y -
Journal of Alternative and... Dec 2020To assess the efficacy and safety of mecobalamin on peripheral neuropathy. Mecobalamin is an active form of vitamin B12 that has been suggested to be beneficial in... (Meta-Analysis)
Meta-Analysis
To assess the efficacy and safety of mecobalamin on peripheral neuropathy. Mecobalamin is an active form of vitamin B12 that has been suggested to be beneficial in improving nerve conduction and neuropathic pain symptoms. Although it is already widely used in Asia for the treatment of peripheral neuropathies, its efficacy remains unclear. Relevant electronic databases were systematically searched for randomized controlled trials investigating the efficacy and safety of mecobalamin on peripheral neuropathy, from inception through December 2019. Study selection, data extraction, and quality assessment were performed independently by two reviewers. The clinical therapeutic efficacy, pain score, neuropathic symptom score, nerve conduction velocities (NCVs), and adverse events of mecobalamin were assessed and were pooled by using a random-effects model. Heterogeneity was assessed by and chi-squared tests. Fifteen studies with 1707 peripheral neuropathy patients caused by diabetic peripheral neuropathy and herpetic neuropathy were included. Based on Cochrane's risk of bias criteria, most of the included studies (11/15, 73%) were rated high risk of bias, whereas 20% and 7% were rated some concerns and low risk of bias, respectively. In terms of the proportion of patients achieving clinical therapeutic efficacy, mecobalamin alone (risk ratio [RR] = 1.17; 95% confidence interval [CI] 1.03-1.33) and mecobalamin in combination (RR = 1.32; 95% CI 1.21-1.45) are more effective than active control. For NCV outcomes, only mecobalamin combination treatment was effective. Neither mecobalamin alone nor mecobalamin in combination is effective on the pain score and neuropathic symptom outcomes. No serious adverse events associated with mecobalamin were reported during the treatment periods. Our findings indicate that mecobalamin in combination may be effective in improving clinical therapeutic efficacy and NCV outcomes for peripheral neuropathy patients, but the evidence is not clear for mecobalamin alone. More high-quality studies are required to confirm this finding.
Topics: Aged; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Vitamin B 12
PubMed: 32716261
DOI: 10.1089/acm.2020.0068 -
The Cochrane Database of Systematic... May 2023Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma (RCC) has changed fundamentally. Today, combined therapies from different drug categories have a firm place in a complex first-line therapy. Due to the large number of drugs available, it is necessary to identify the most effective therapies, whilst considering their side effects and impact on quality of life (QoL).
OBJECTIVES
To evaluate and compare the benefits and harms of first-line therapies for adults with advanced RCC, and to produce a clinically relevant ranking of therapies. Secondary objectives were to maintain the currency of the evidence by conducting continuous update searches, using a living systematic review approach, and to incorporate data from clinical study reports (CSRs).
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, conference proceedings and relevant trial registries up until 9 February 2022. We searched several data platforms to identify CSRs.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating at least one targeted therapy or immunotherapy for first-line treatment of adults with advanced RCC. We excluded trials evaluating only interleukin-2 versus interferon-alpha as well as trials with an adjuvant treatment setting. We also excluded trials with adults who received prior systemic anticancer therapy if more than 10% of participants were previously treated, or if data for untreated participants were not separately extractable.
DATA COLLECTION AND ANALYSIS
All necessary review steps (i.e. screening and study selection, data extraction, risk of bias and certainty assessments) were conducted independently by at least two review authors. Our outcomes were overall survival (OS), QoL, serious adverse events (SAEs), progression-free survival (PFS), adverse events (AEs), the number of participants who discontinued study treatment due to an AE, and the time to initiation of first subsequent therapy. Where possible, analyses were conducted for the different risk groups (favourable, intermediate, poor) according to the International Metastatic Renal-Cell Carcinoma Database Consortium Score (IMDC) or the Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Our main comparator was sunitinib (SUN). A hazard ratio (HR) or risk ratio (RR) lower than 1.0 is in favour of the experimental arm.
MAIN RESULTS
We included 36 RCTs and 15,177 participants (11,061 males and 4116 females). Risk of bias was predominantly judged as being 'high' or 'some concerns' across most trials and outcomes. This was mainly due to a lack of information about the randomisation process, the blinding of outcome assessors, and methods for outcome measurements and analyses. Additionally, study protocols and statistical analysis plans were rarely available. Here we present the results for our primary outcomes OS, QoL, and SAEs, and for all risk groups combined for contemporary treatments: pembrolizumab + axitinib (PEM+AXI), avelumab + axitinib (AVE+AXI), nivolumab + cabozantinib (NIV+CAB), lenvatinib + pembrolizumab (LEN+PEM), nivolumab + ipilimumab (NIV+IPI), CAB, and pazopanib (PAZ). Results per risk group and results for our secondary outcomes are reported in the summary of findings tables and in the full text of this review. The evidence on other treatments and comparisons can also be found in the full text. Overall survival (OS) Across risk groups, PEM+AXI (HR 0.73, 95% confidence interval (CI) 0.50 to 1.07, moderate certainty) and NIV+IPI (HR 0.69, 95% CI 0.69 to 1.00, moderate certainty) probably improve OS, compared to SUN, respectively. LEN+PEM may improve OS (HR 0.66, 95% CI 0.42 to 1.03, low certainty), compared to SUN. There is probably little or no difference in OS between PAZ and SUN (HR 0.91, 95% CI 0.64 to 1.32, moderate certainty), and we are uncertain whether CAB improves OS when compared to SUN (HR 0.84, 95% CI 0.43 to 1.64, very low certainty). The median survival is 28 months when treated with SUN. Survival may improve to 43 months with LEN+PEM, and probably improves to: 41 months with NIV+IPI, 39 months with PEM+AXI, and 31 months with PAZ. We are uncertain whether survival improves to 34 months with CAB. Comparison data were not available for AVE+AXI and NIV+CAB. Quality of life (QoL) One RCT measured QoL using FACIT-F (score range 0 to 52; higher scores mean better QoL) and reported that the mean post-score was 9.00 points higher (9.86 lower to 27.86 higher, very low certainty) with PAZ than with SUN. Comparison data were not available for PEM+AXI, AVE+AXI, NIV+CAB, LEN+PEM, NIV+IPI, and CAB. Serious adverse events (SAEs) Across risk groups, PEM+AXI probably increases slightly the risk for SAEs (RR 1.29, 95% CI 0.90 to 1.85, moderate certainty) compared to SUN. LEN+PEM (RR 1.52, 95% CI 1.06 to 2.19, moderate certainty) and NIV+IPI (RR 1.40, 95% CI 1.00 to 1.97, moderate certainty) probably increase the risk for SAEs, compared to SUN, respectively. There is probably little or no difference in the risk for SAEs between PAZ and SUN (RR 0.99, 95% CI 0.75 to 1.31, moderate certainty). We are uncertain whether CAB reduces or increases the risk for SAEs (RR 0.92, 95% CI 0.60 to 1.43, very low certainty) when compared to SUN. People have a mean risk of 40% for experiencing SAEs when treated with SUN. The risk increases probably to: 61% with LEN+PEM, 57% with NIV+IPI, and 52% with PEM+AXI. It probably remains at 40% with PAZ. We are uncertain whether the risk reduces to 37% with CAB. Comparison data were not available for AVE+AXI and NIV+CAB.
AUTHORS' CONCLUSIONS
Findings concerning the main treatments of interest comes from direct evidence of one trial only, thus results should be interpreted with caution. More trials are needed where these interventions and combinations are compared head-to-head, rather than just to SUN. Moreover, assessing the effect of immunotherapies and targeted therapies on different subgroups is essential and studies should focus on assessing and reporting relevant subgroup data. The evidence in this review mostly applies to advanced clear cell RCC.
Topics: Male; Female; Adult; Humans; Carcinoma, Renal Cell; Axitinib; Nivolumab; Network Meta-Analysis; Sunitinib
PubMed: 37146227
DOI: 10.1002/14651858.CD013798.pub2 -
Nutrition Reviews Mar 2022Elevation of homocysteine (Hcy) levels is well-established as a risk factor for dementia, yet controversy exists regarding whether B-vitamin-mediated reduction of... (Meta-Analysis)
Meta-Analysis
CONTEXT
Elevation of homocysteine (Hcy) levels is well-established as a risk factor for dementia, yet controversy exists regarding whether B-vitamin-mediated reduction of homocysteine levels can benefit cognitive function.
OBJECTIVE
To investigate whether B vitamin supplementation can reduce the risk of cognitive decline and incident dementia.
DATA SOURCES
The PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched for articles published from the inception dates to March 1, 2020. Randomized controlled trials (RCT) were included if B vitamins were supplied to investigate their effect on the rate of cognitive decline. Cohort studies investigating dietary intake of B vitamins and the risk of incident dementia were eligible. Cross-sectional studies comparing differences in levels of B vitamins and Hcy were included.
DATA EXTRACTION
Two reviewers independently performed data extraction and assessed the study quality.
DATA ANALYSIS
Random-effect or fixed-effect models, depending on the degree of heterogeneity, were performed to calculate mean differences (MDs), hazard ratios (HRs), and odds ratios (ORs).
RESULTS
A total of 95 studies with 46175 participants (25 RCTs, 20 cohort studies, and 50 cross-sectional studies) were included in this meta-analysis. This meta-analysis supports that B vitamins can benefit cognitive function as measured by Mini-Mental State Examination score changes (6155 participants; MD, 0.14, 95%CI 0.04 to 0.23), and this result was also significant in studies where placebo groups developed cognitive decline (4211 participants; MD, 0.16, 95%CI 0.05 to 0.26), suggesting that B vitamins slow cognitive decline. For the > 12 months interventional period stratum, B vitamin supplementation decreased cognitive decline (3814 participants; MD, 0.15, 95%CI 0.05 to 0.26) compared to placebo; no such outcome was detected for the shorter interventional stratum (806 participants; MD, 0.18, 95%CI -0.25 to 0.61). In the non-dementia population, B vitamin supplementation slowed cognitive decline (3431 participants; MD, 0.15, 95%CI 0.04 to 0.25) compared to placebo; this outcome was not found for the dementia population (642 participants; MD, 0.20, 95%CI -0.35 to 0.75). Lower folate levels (but not B12 or B6 deficiency) and higher Hcy levels were significantly associated with higher risks of dementia (folate: 6654 participants; OR, 1.76, 95%CI 1.24 to 2.50; Hcy: 12665 participants; OR, 2.09, 95%CI 1.60 to 2.74) and cognitive decline (folate: 4336 participants; OR, 1.26, 95%CI 1.02 to 1.55; Hcy: 6149 participants; OR, 1.19, 95%CI 1.05 to 1.34). Among the population without dementia aged 50 years and above, the risk of incident dementia was significantly decreased among individuals with higher intake of folate (13529 participants; HR, 0.61, 95%CI 0.47 to 0.78), whereas higher intake of B12 or B6 was not associated with lower dementia risk.
CONCLUSIONS
This meta-analysis suggests that B vitamin supplementation is associated with slowing of cognitive decline, especially in populations who received early intervention and intervention of long duration; the study also indicates that higher intake of dietary folate, but not B12 or B6, is associated with a reduced risk of incident dementia in non-dementia aged population. Given the prevalence of dementia cases in many countries with aging populations, public health policies should be introduced to ensure that subgroups of the population at risk have an adequate B vitamin status.
Topics: Aged; Cognition; Cognitive Dysfunction; Dementia; Dietary Supplements; Folic Acid; Humans; Middle Aged; Vitamin B 12; Vitamin B Complex
PubMed: 34432056
DOI: 10.1093/nutrit/nuab057 -
Nutrients May 2023Breast milk is tailored for optimal growth in all infants; however, in some infants, it is related to a unique phenomenon referred to as breast milk jaundice (BMJ). BMJ... (Review)
Review
Breast milk is tailored for optimal growth in all infants; however, in some infants, it is related to a unique phenomenon referred to as breast milk jaundice (BMJ). BMJ is a type of prolonged unconjugated hyperbilirubinemia that is often late onset in otherwise healthy-appearing newborns, and its occurrence might be related to breast milk itself. This review aims to systematically evaluate evidence regarding breast milk composition and the development of BMJ in healthy neonates. PubMed, Scopus and Embase were searched up to 13 February 2023 with key search terms, including neonates, hyperbilirubinemia, and breastfeeding. A total of 678 unique studies were identified and 12 were ultimately included in the systematic review with narrative synthesis. These included studies covered both nutritional compositions (e.g., fats and proteins) and bioactive factors (e.g., enzymes and growth factors) of breast milk and formally assessed the difference in the concentration (or presence) of various endogenous components of breast milk collected from mothers of BMJ infants and healthy infants. The results were inconsistent and inconclusive for most of the substances of interest, and there was only a single study available (e.g., total energy and mineral content, bile salts and cytokines); conflicting or even contradictory results arose when there were two or more studies on the subject matter (e.g., fats and free fatty acids contents and epidermal growth factor). The etiology of BMJ is likely multifactorial, and no single constituent of breast milk could explain all the BMJ cases observed. Further well-designed studies are warranted to investigate the complex interaction between maternal physiology, the breast milk system and infant physiology before this field could be progressed to uncover the etiology of BMJ.
Topics: Infant; Female; Humans; Infant, Newborn; Milk, Human; Bilirubin; Jaundice, Neonatal; Breast Feeding; Hyperbilirubinemia; Jaundice
PubMed: 37242142
DOI: 10.3390/nu15102261 -
Nutrition Reviews Jul 2023The popularity of plant-based diets, characterized by a partial or complete exclusion of animal products, has increased significantly over the last 10 years. The... (Meta-Analysis)
Meta-Analysis
CONTEXT
The popularity of plant-based diets, characterized by a partial or complete exclusion of animal products, has increased significantly over the last 10 years. The exclusion of animal products removes the most common sources of vitamin B12, which can lead to vitamin B12 deficiency and result in irreversible damage, such as growth stunting.
OBJECTIVE
This aim of this systematic review and meta-analysis was to qualitatively evaluate all studies on this subject and to quantify the potential difference in vitamin B12 levels in healthy children and adolescents aged 5 to 18 years.
DATA SOURCES
PubMed and Embase databases were searched for relevant studies investigating vitamin B12 levels in healthy children and adolescents aged 5 to 18 years on plant-based diets.
DATA EXTRACTION
Studies were assessed qualitatively with the AXIS tool and quantitatively with Stata 16.0 software.
DATA ANALYSIS
Overall, children and adolescents on plant-based diets had a significantly lower vitamin B12 level than omnivorous children and adolescents (-97 pmol/L; 95%CI, -187 to -7; I2 = 98.5%), a difference that remained statistically significant after adjusting for methodological confounders. After subgroup analyses, this effect was not statistically significant for children and adolescents on vegetarian diets but remained significant in children and adolescents on vegan or macrobiotic diets. Moreover, total vitamin B12 intake nullified the mean difference in vitamin B12 levels.
CONCLUSION
Despite high heterogeneity across studies, these results indicate that children and adolescents on plant-based diets, especially those on vegan and macrobiotic diets, may be at risk of developing vitamin B12 deficiency.
Topics: Child; Humans; Diet; Diet, Vegetarian; Nutritional Status; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 36413044
DOI: 10.1093/nutrit/nuac096 -
Journal of Cardiothoracic and Vascular... Sep 2023Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating... (Meta-Analysis)
Meta-Analysis Review
Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue.
Topics: Adult; Humans; Hydroxocobalamin; Methylene Blue; Vasodilation; Vasoplegia; Shock; Hypotension
PubMed: 37147207
DOI: 10.1053/j.jvca.2023.04.006 -
Veterinary and Comparative Oncology Jun 2022The use of tyrosine kinase inhibitors (TKI) has gained significant importance in veterinary cancer patients over the last decade. Toceranib phosphate has been licensed... (Review)
Review
The use of tyrosine kinase inhibitors (TKI) has gained significant importance in veterinary cancer patients over the last decade. Toceranib phosphate has been licensed for the treatment of dogs with mast cell tumours. Its molecular similarity to sunitinib, a TKI used in human medicine, has led many veterinary oncologists to use this agent for multiple neoplastic diseases. The aim of the current study was to perform a systematic review of the evidence for the use of toceranib in dogs with non-mast cell neoplasia. Two electronic databases were searched. Publications were included if toceranib was used as a treatment option in canine patients. Studies and case reports were excluded if toceranib was used as part of a multi-modal treatment plan and response or outcome data related to toceranib therapy were not described. A total of 28 studies were included from 122 references. The most common types of neoplasias identified were neuroendocrine tumours, anal gland sac adenocarcinoma, and osteosarcoma. Multiple other neoplasias had one or two studies identified to describe the use of toceranib. Results of the study support that toceranib phosphate may have efficacy against certain types of neoplasia under certain conditions, such as neuroendocrine tumours, gastrointestinal stromal tumours and anal sac adenocarcinomas, while it is probably not effective for the management of metastatic osteosarcoma based on the findings of the review.
Topics: Animals; Antineoplastic Agents; Bone Neoplasms; Dog Diseases; Dogs; Humans; Indoles; Osteosarcoma; Pyrroles
PubMed: 34981886
DOI: 10.1111/vco.12799