Efficacy and safety of transcranial magnetic stimulation for treating major depressive disorder: An umbrella review and re-analysis of published meta-analyses of randomised controlled trials.

OBJECTIVES: We re-analysed data from published meta-analyses testing the effects of Transcranial Magnetic Stimulation (TMS) on Major Depressive Disorder (MDD) in adults. We applied up-to-date meta-analytic techniques for handling heterogeneity including the random-effects Hartung-Knapp-Sidik-Jonkman method and estimated 95% prediction intervals. Heterogeneity practices in published meta-analyses were assessed as a secondary aim. STUDY DESIGN AND SETTING: We performed systematic searches of systematic reviews with meta-analyses that included randomised controlled trials assessing the efficacy, tolerability, and side effects of TMS on MDD. We performed risk of bias assessment using A MeaSurement Tool to Assess Reviews (AMSTAR) 2 and re-analysed meta-analyses involving 10 or more primary studies. RESULTS: We included 29 systematic reviews and re-analysed 15 meta-analyses. Authors of all meta-analyses interpreted findings to suggest TMS is safe and effective for MDD. Our re-analysis showed that in 14 out of 15 meta-analyses, the 95% prediction intervals included the null and captured values in the opposite effect direction. We also detected presence of small-study effects in some meta-analyses and 24 out of 25 systematic reviews received an AMSTAR 2 rating classed as critically low. CONCLUSION: Authors of all included meta-analyses interpreted findings to suggest TMS is safe and effective for MDD despite lack of comprehensive investigation of heterogeneity. Our re-analysis revealed the direction and magnitude of treatment effects vary widely across different settings. We also found high risk of bias in the majority of included systematic reviews and presence of small-study effects in some meta-analyses. Because of these reasons, we argue TMS for MDD may not be as effective and potentially less tolerated in some populations than current evidence suggests.

The benefit of dynamic neutrophil-lymphocyte ratio and systemic immune-inflammation index in predicting survival in patients undergoing hemiarthroplasty.

OBJECTIVE: We aimed at investigating the relationship between the values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) in the preoperative and postoperative periods in patients who underwent hemiarthroplasty. PATIENTS AND METHODS: The medical records of patients aged >65 years who underwent hemiarthroplasty due to hip fracture in our institution between January 2017 and December 2020 were examined. Dynamic Neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (dPLR), and systemic immune-inflammation index (dSII) were calculated using biomarker data (neutrophil, lymphocyte, and platelet counts) obtained at admission and on postoperative day 2 and 5. RESULTS: A total of 176 individuals (119 females, 57 males) were included in the study. The PLR on postoperative day 2, and NLR and SII measurement on postoperative day 2 and 5 in patients were found to have significant predictive value in 1-year mortality rates. A 1-year increase in age was associated with a 4.9% increased risk of death at 1-year follow-up (p=0.006). A 1-unit increase in NLR on postoperative day 5 was associated with a 4.3% increased risk of death at 1-year follow-up (p=0.004). CONCLUSIONS: The present study shows that our model for predicting the absolute mortality risk in patients can be improved by evaluating dSII, dPLR, and dNLR in the preoperative period and postoperative day 2 and 5. However, it cannot be said that the model has a discriminatory ability to exactly predict postoperative mortality. Nevertheless, these parameters may aid in the development of early therapeutic intervention to improve patient outcomes.

Bone mineral density (BMD) and neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) in childhood thyroid diseases.

OBJECTIVE: This study aimed at investigating the laboratory parameters related to the pathogenesis of bone loss, including bone mineral density (BMD), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) in children with thyroid disease and healthy controls. PATIENTS AND METHODS: Children and adolescents with hypothyroidism (n=63) and hyperthyroidism (n=30) as well as 32 age- and sex-matched healthy controls were included in the study. Auxological data, BMD, hemogram parameters, the levels of thyroid hormone, thyroid stimulating hormone (TSH), thyroid autoantibodies, parathyroid hormone, 25-hydroxy vitamin D, alkaline phosphatase, calcium, and phosphorus were analyzed. RESULTS: The mean age of the patients was 12.12±2.7 years (range: 8-17). BMD Z-scores were within the normal range in all the patients and healthy controls. The BMD Z-scores were significantly higher in patients with hyperthyroidism than those in the control group and in patients with hypothyroidism. No significant difference was observed between the control and hypothyroid groups in terms of the BMD Z-scores. A correlation was observed between the BMD Z-scores and NLR, MLR, PLR, and free T4 levels. In patients with hypothyroidism, the BMD Z-scores were significantly positively correlated with the NLR, MLR, PLR, and the TSH level. In the control group, there was a moderate positive correlation between the BMD Z-scores and NLR. In the hyperthyroid group, there were no significant correlations between the BMD Z-scores and other variables. CONCLUSIONS: The study data suggest that in children and adolescents with thyroid disease, the relationship between the BMD Z-scores and NLR, MLR, and PLR at the initial diagnosis in the hypothyroidism group was different from that in their healthy peers.

Bone mineral density and complete blood count ratios in children and adolescents with obesity.

OBJECTIVE: Monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-high-density lipoprotein ratio (MHR), and mean platelet volume (MPV) are considered novel inflammatory markers. In this study, we aimed to investigate the relationship between bone mineral density (BMD) Z score and blood cell composition in children and adolescents with obesity and to create a suitable index for the diagnosis of obesity-associated osteoporosis. PATIENTS AND METHODS: We included 148 children, comprising 112 children with obesity (obese group) and 36 sex- and age-matched healthy children (normal weight) (control group). Patient details acquired from medical records were used to measure blood count levels; BMD, using dual-energy X-ray absorptiometry; and BMD Z-scores, using race and sex specific curves. RESULTS: Mean BMD Z score in the obese and normal weight group was within the normal limits and significantly higher in the obese group. The BMD Z score showed a significant relationship with MLR and PLR. Patient BMD Z-scores were negatively correlated with MLR and PLR in the obese group and positively correlated in the control group. In addition, a positive correlation was found between BMD Z score and NLR in the control group. CONCLUSIONS: Our study outcomes show that there may be a relationship between bone mass and inflammation expressed as PLR and MLR in obese children and adolescents. PLR and MLR, which are common indicators of morbidity and mortality in many chronic inflammatory diseases, may also be useful for evaluating bone status in children with obesity. However, further research on the subject is warranted.

Epidemiology of chronic pain and its treatment in The Netherlands.

BACKGROUND: Chronic pain is common; however, good epidemiological data are scarce. Such information can help all the involved stakeholders to make responsible decisions about health budgets and prioritisation. This study aims to provide best-evidence epidemiological information about chronic pain in the Netherlands. METHODS: We performed a systematic search which yielded 16,619 references, 119 Dutch studies were relevant. We selected at least three studies per question that provided the most recent, representative and valid data. RESULTS: The prevalence of moderate to severe general chronic pain among Dutch adults was estimated at 18%. This prevalence was 27% and 55% for any cancer pain. Up to 74% of patients with general or non-cancer chronic pain get treated; this percentage is little higher for patients with cancer pain. A substantial proportion of the patients receive drug treatment for their pain, mainly NSAIDs, but also non-pharmacological interventions for pain are being used. Up to 43% of the chronic non-cancer pain patients report not receiving treatment and up to 79% of the patients believe their pain is inadequately treated. All studies reported a detrimental effect of chronic pain on quality of life, activities of daily living and mental health. Chronic pain is also associated with direct and indirect medical costs, and patients may have decreased income and additional out-of pocket expenses. CONCLUSION: Chronic pain occur s frequently, has a negative impact on the patient and society and treatment may not always be adequate. Chronic pain should be seen as an important public health problem deserving more attention of Dutch healthcare workers and policy makers.

5% lidocaine-medicated plaster vs other relevant interventions and placebo for post-herpetic neuralgia (PHN): a systematic review.

Several pharmacological treatments are used to manage post-herpetic neuralgia (PHN). The use of topical analgesics, such as 5% lidocaine-medicated plaster (5% LMP), may be preferable to systemic treatments in that they are formulated to produce a local pain relieving effect with minimal systemic absorption. However, direct head-to-head comparisons are relatively few, and a rigorous assessment of the relative efficacy and safety of the various treatment options is lacking. The objective of this study was to compare 5% LMP for the relief of PHN with other relevant interventions and placebo. Six databases were searched up to May 2010. Quantitative methods for data synthesis were used, and a network meta-analysis was conducted. Twenty unique studies (32 publications) were included. Placebo-controlled studies showed 5% LMP to be effective in providing pain relief and reducing allodynia while adverse event rates were generally low. A comparison between 5% LMP and pregabalin indicated the non-inferiority of 5% LMP for pain reduction and showed greater improvement of quality of life for 5% LMP. Adverse events (AE) were significantly fewer with 5% LMP. In the network meta-analysis, only 5% LMP and gabapentin were associated with a greater change in pain from baseline than placebo [-15.50 (95% CI -18.85 to -12.16) and -7.56 (95% CI -12.52 to -2.59) respectively]. 5% LMP was shown to be more effective than capsaicin [-16.45 (95% CI -20.04 to -12.86)], gabapentin [-7.95 (95% CI -13.29 to -2.61)] and pregabalin [-13.45 (95% CI -19.19 to -7.71)]. For pain relief, two comparators were more effective than placebo [mean pain relief, gabapentin: 32.77 (95% CI 15.57-49.97); 5% LMP: 26.77 (95% CI 9.11-44.43)]. 5% LMP was shown to be comparable to gabapentin [-6.00 (95% CI -25.32-13.32)]. The results suggest that 5% LMP and gabapentin have similar effects on pain relief and that 5% LMP is more effective than capsaicin and pregabalin (change in pain from baseline). Topical agents, such as 5% LMP, are associated with fewer and less clinically significant AE than is the case for systemic agents. However, small numbers, and limited size and quality of included studies should be taken into account. Further studies are needed.